Institut für Ernährungswissenschaften

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Anthropometrics, hemoglobin status and dietary micronutrient intake among Tanzanian and Mozambican pigeon pea farmers
(2022) Eleraky, Laila; Issa, Ramula; Maciel, Sónia; Mbwana, Hadijah; Rybak, Constance; Frank, Jan; Stuetz, Wolfgang
Inadequate consumption of micronutrient-dense and protein-rich foods such as vegetables, legumes and meat is an important contributing cause for anemia and deficiencies of vitamin A and iron in rural communities of Tanzania and Mozambique. A cross-sectional study was conducted to assess the nutritional status (anthropometrics and hemoglobin) and diets in particular micronutrient intake of female and male pigeon pea farmers from Lindi, Tanzania, and Gurué, the Zambézia province of Mozambique. A total of 1526 farmers (669 from Tanzania, 857 from Mozambique) were studied, of whom 16% were overweight and 35% were anemic. The highest prevalence of overweight and anemia, at 35% and 48%, was observed in Tanzanian and Mozambican women, respectively. Overall, only a small proportion of women and men reached the recommended daily dietary intake of vitamin A (10%), iron (51%) and zinc (44%). Multiple regression models revealed that dark green leafy vegetables (DGLVs) highly predicted vitamin A intake, whereas legumes in Tanzania and starchy plants in Mozambique were actually the dominant sources of vitamin A. Cereals covered over half of the iron and the zinc intake in both countries. An increased consumption of micronutrient-rich DGLVs and legumes, while reducing the high amounts of refined maize or polished rice, is suggested to counteract the high prevalence of anemia and overweight among smallholder farmers in East and South Eastern Africa.
Baseline assessment and effect of a supplementary community-based nutrition intervention study on the prevention/treatment of anemia among young Adivasi children in West Bengal, India
(2020) Stiller, Caroline K.; Biesalski, Hans-Konrad
Background: India´s Adivasi scheduled tribe population is disproportionately affected by anemia and undernutrition. On the avenue to sustainably promote child health locally available resources have to be maxed out. Subsequently, designed recipes may find entrance and modify dietary routines on household level, through interactive home-based cooking trainings, community awareness and homestead food production. Study design: From February 2015 onwards, the cluster-randomized controlled feeding trial was conducted in 21 tribal villages Birbhum District, West Bengal. The intervention lasted for 18 months and embraced four assessment points (t0, t6, t12, t18) including medical checkup, measurement of Hb concentrations (HemoCue Hb201+) as well as anthropometric indices. A semi-structured household (HH) survey was part of the baseline assessment. The research comprises one control group (CG) and three intervention groups (diversified meals only (IG1), with the addition of locally producible Amaranthus tricolor/Moringa oleifera leaf powders (ALP/MLP) in the ratio 2:1 (IG2), or with an adjusted amount of commercially produced micronutrient powder (MNP) TopNutri (IG3)). Supplementary meals were provided three times a week during an on-the-spot community feeding program. 293 children (6-39 months) were valid for the pre-/post intervention effect analysis. Objectives: To assess the overall burden of anemia and undernutrition and to investigate nutrition-sensitive and nutrition-specific factors determining the maternal and child nutritional status at baseline, moreover to identify independent drivers of anemia in Adivasi children (Article I and II). To design improved recipes and to evaluate their effect in a supplementary feeding intervention on the primary outcome variable hemoglobin (Hb), and the secondary outcome variables stunting (HAZ), underweight (WAZ), and wasting (WHZ) (Article III). The first article (Chapter 4) provides data on the maternal nutritional status and child feeding practices, and describes socio-demographic characteristics, family planning methods, use of antenatal care services and birth, childcare, mother-child dyad analysis. Moderate/severe forms of anemia and underweight were prevalent in every second mother. Child feeding practices and child caring were found to be suboptimal. Infants (6 to 11 months) were particularly vulnerable with merely every fourth child fulfilling the minimum acceptable diet (2 to 3 meals per day and  4 food groups (FG) per day). On HH level the serving of animal-sourced foods, legumes, vegetables and fruits has to be scaled up. The second article (Chapter 5) assessed the prevalence of anemia and undernutrition among Santal Adivasi children, determined independent predictors of moderate/severe anemia, and depicted agricultural assets, livelihood, aspects of food security and hygiene, morbidity rates, health seeking behavior. Binary Logistic regression assessed five independent predictors of moderate/severe anemia in children (Hb<10g/dl): child´s age<24 months, low WAZ scores, any morbidity (fever, diarrhea, or respiratory infection), low maternal Hb concentrations, lack of dietary diversification (low count of FG consumed during the previous 24 hours). The third arcticle (Chapter 6) assessed the intervention effects of the three study meals on the prevention/treatment of anemia (and undernutrition) in Adivasi children. IG1 (diversified meals only) showed significant higher Hb concentrations as compared to CG during the intervention (adjusted for age and Hb concentrations at baseline, time between assessment points, and gender). The mean Hb of IG2 or IG3, remained comparable to CG. Concluding remarks: Distressing rates of anemia and undernutrition were found among Adivasi mothers and children. To address identified drivers of anemia in Adivasi children and lower the burden of undernutrition multi-sectoral programmatic actions comprising the key pillars nutrition, agriculture and health care are recommended for timely intervention before the child reaches two years of age; accompanied by hygienic and sanitary activities, with interactive awareness trainings being in the center of actions. Lack of dietary diversification was not only found as predictor for anemia at baseline, moreover the low-dose intervention trial confirmed diversified meals only (IG1) being a successful food-based approach in significantly increasing the Hb concentration as opposed to the CG, thus is suggested as useful preventive strategy to overcome nutrition-related anemia amongst Santal Adivasi children (aside iron therapy). Study findings indicate the adding of MNP (IG3) as being beneficial for decreasing the burden of undernutrition and infectious diseases.
Characterization of dietary and genetic influences on the gastrointestinal microbiota
(2023) Bubeck, Alena Marie; Fricke, Florian W.
Although the gut microbiota is known to contribute fundamentally to human health, e.g. by promoting the maturation of the immune system and intestinal homeostasis, the factors shaping its composition are only poorly understood. Extrinsic and intrinsic influences can disturb the tightly controlled equilibrium between the microbiome and the host and induce dysbiosis, which has been linked to diverse health conditions such as obesity, atherosclerotic cardiovascular disease (ACVD) and inflammatory bowel disease (IBD). Therefore, understanding events leading to microbial perturbations and the prediction of associated health outcomes could aid in the prevention and treatment of these conditions. In this work, the impact of dietary and genetic factors on gastrointestinal microbiota compositions were determined, with the diet serving as an exemplary extrinsic, modifiable microbiota-relevant factor and with a genetic deficiency in a mouse model for intestinal inflammation serving as an exemplary intrinsic, non-modifiable microbiota-relevant factor. In both studies, microbial communities obtained from either a human or a murine cohort, respectively, were taxonomically characterized by 16S rRNA gene amplicon sequencing and analyzed in the context of metabolic and inflammatory implications for the host. In ACVD, the reduction of excess blood cholesterol, which is a main risk factor, is tackled by clinical interventions aiming to reduce cholesterol uptake from exogenous, dietary sources or by inhibiting endogenous cholesterol biosynthesis. Cholesterol-to-coprostanol conversion by the intestinal microbiota has also been suggested to reduce intestinal and serum cholesterol availability, but the dependencies of cholesterol conversion on specific bacterial taxa and dietary habits, as well as its association with serum lipid levels remain largely unknown. To study microbiota contributions to human cholesterol metabolism under varying conditions, fecal microbiota and lipid profiles, as well as serum lipid biomarkers, were determined in two independent human cohorts, including individuals with (CARBFUNC study) and without obesity (KETO study) on very low-carbohydrate high-fat diets (LCHF) for three to six months and six weeks, respectively. Across these two geographically independent studies, conserved distributions of cholesterol high and low-converter types were measured. Also, cholesterol conversion was most dominantly linked to the relative abundance of the cholesterol-converting bacterial species Eubacterium coprostanoligenes, which was further increased in low-converters by LCHF diets, shifting them towards a high-conversion state. Lean cholesterol high-converters, which were characterized by adverse serum lipid profiles even before the LCHF diet, responded to the intervention with increased LDL-C, independently of fat, cholesterol and saturated fatty acid intake. These findings identify the cholesterol high-converter type as a potential predictive biomarker for an increased LDL-C response to LCHF diet in metabolically healthy lean individuals. Although the etiology of IBD has not been fully resolved, an interplay between the intestinal microbiota, environmental factors and an individual’s genetic susceptibility is thought to trigger chronic inflammation by a dysregulation of the immune response in the gut. To identify colitis-associated microbiota alterations throughout the development of spontaneous colitis, mice with a genetic deficiency of the anti-inflammatory cytokine Interleukin-10 (IL-10) from different litters were co-housed with wild-type mice and monitored for 20 weeks. The scoring of mice based on their phenotype and stool consistency mirrored the state of mucosal inflammation as assessed based on histopathological examinations and cytokine expression profiles. Also, the state of colitis was characterized by global microbiota alterations and susceptibility to colitis was dependent on litter-specific microbiome compositions that mice adopted early on in their lives. Colitis development was further associated with the presence of the bacterial genus Akkermansia in mature mice shortly before symptoms manifested. This genus was also a good predictor of colitis-related mice withdrawal, suggesting the potential of Akkermansia to serve as an early onset, subclinical colitis marker. In summary, fecal microbiota characterizations in response to LCHF diets in humans and throughout the development of intestinal inflammation in a colitis mouse model highlight the potential of personalized microbiome-based patient classifications to predict clinical outcomes and improve treatment approaches.
Dietary intake of fructooligosaccharides protects against metabolic derangements evoked by chronic exposure to fructose or galactose in rats
(2023) Almasri, Fidèle; Collotta, Debora; Aimaretti, Eleonora; Sus, Nadine; Aragno, Manuela; Dal Bello, Federica; Eva, Carola; Mastrocola, Raffaella; Landberg, Rikard; Frank, Jan; Collino, Massimo
Scope: Diets rich in fat and sugars evoke chronic low-grade inflammation, leading to metabolic derangements. This study investigates the impact of fructose and galactose, two commonly consumed simple sugars, on exacerbation of the harmful effects caused by high fat intake. Additionally, the potential efficacy of fructooligosaccharides (FOS), a fermentable dietary fiber, in counteracting these effects is examined. Methods and results: Male Sprague-Dawley rats (six/group) are fed 8 weeks as follows: control 5% fat diet (CNT), 20% fat diet (FAT), FAT+10% FOS diet (FAT+FOS), FAT+25% galactose diet (FAT+GAL), FAT+GAL+10% FOS diet (FAT+GAL+FOS), FAT+25% fructose diet (FAT+FRU), FAT+FRU+10% FOS diet (FAT+FRU+FOS). The dietary manipulations tested do not affect body weight gain, blood glucose, or markers of systemic inflammation whereas significant increases in plasma concentrations of triacylglycerols, cholesterol, aspartate aminotransferase, and alanine aminotrasferase are detected in both FAT+FRU and FAT+GAL compared to CNT. In the liver and skeletal muscle, both sugars induce significant accumulation of lipids and advanced glycation end-products (AGEs). FOS supplementation prevents these impairments. Conclusion: This study extends the understanding of the deleterious effects of a chronic intake of simple sugars and demonstrates the beneficial role of the prebiotic FOS in dampening the sugar-induced metabolic impairments by prevention of lipid and AGEs accumulation.
Disparities in health and nutrition between semi-urban and rural mothers and birth outcomes of their newborns in Bukavu, DR Congo: A baseline assessment
(2023) Beitze, Damaris Elisabeth; Malengera, Céline Kavira; Kabesha, Theophile Barhwamire; Frank, Jan; Scherbaum, Veronika
Aim: This research aimed to evaluate health and nutritional practices of mothers during pregnancy and birth outcomes of their newborns in Bukavu, Democratic Republic of the Congo (DRC), comparing semi-urban and rural areas. Background: Health and nutrition during pregnancy are crucial for adequate development of the fetus. Health care plays an important role but is often poor in rural areas of developing countries. Methods: A baseline survey of a nutritional follow-up study was conducted in two semi-urban and one rural hospital in the vicinity of Bukavu, DRC. In total, 471 mother-child pairs were recruited after delivery. Data collection included socio-demographic parameters, nutrition and health measures during pregnancy, and anthropometric parameters. Semi-urban and rural study locations were compared and predictors of birth weight evaluated. Findings: Semi-urban and rural mothers differed significantly in nutrition and health practices during pregnancy, as well as birth outcomes. In the rural area, there was a higher rate of newborns with low birth weight (10.7%) and lower rates of antimalarial medication (80.8%), deworming (24.6%), consumption of nutritional supplements (81.5%), and being informed about nutrition by medical staff (32.8%) during pregnancy as well as practicing family planning (3.1%) than in the semi-urban areas (2.7%, 88.6%, 88.3%; 89.3%, 46.5%, and 17.1%, respectively). Birth weight was positively predicted by increasing maternal MUAC, age, and gestational age and negatively by rural location, being primipara, being a farmer, and female newborn sex. Conclusion: The findings highlight the importance of strengthening antenatal care activities especially in rural areas in order to ameliorate both maternal and infantile health and ensure appropriate development.
Effect of a diet rich in galactose or fructose, with or without fructooligosaccharides, on gut microbiota composition in rats
(2022) Mhd Omar, Nor Adila; Dicksved, Johan; Kruger, Johanita; Zamaratskaia, Galia; Michaëlsson, Karl; Wolk, Alicja; Frank, Jan; Landberg, Rikard
Recent studies suggest that a diet rich in sugars significantly affects the gut microbiota. Adverse metabolic effects of sugars may partly be mediated by alterations of gut microbiota and gut health parameters, but experimental evidence is lacking. Therefore, we investigated the effects of high intake of fructose or galactose, with/without fructooligosaccharides (FOS), on gut microbiota composition in rats and explored the association between gut microbiota and low-grade systemic inflammation. Sprague–Dawley rats (n = 6/group) were fed the following isocaloric diets for 12 weeks (% of the dry weight of the sugars or FOS): (1) starch (control), (2) fructose (50%), (3) galactose (50%), (4) starch+FOS (15%) (FOS control), (5) fructose (50%)+FOS (15%), (6) galactose (50%)+FOS (15%), and (7) starch+olive (negative control). Microbiota composition in the large intestinal content was determined by sequencing amplicons from the 16S rRNA gene; 341F and 805R primers were used to generate amplicons from the V3 and V4 regions. Actinobacteria, Verrucomicrobia, Tenericutes, and Cyanobacteria composition differed between diets. Bifidobacterium was significantly higher in all diet groups where FOS was included. Modest associations between gut microbiota and metabolic factors as well as with gut permeability markers were observed, but no associations between gut microbiota and inflammation markers were observed. We found no coherent effect of galactose or fructose on gut microbiota composition. Added FOS increased Bifidobacterium but did not mitigate potential adverse metabolic effects induced by the sugars. However, gut microbiota composition was associated with several metabolic factors and gut permeability markers which warrant further investigations.
Entwicklung und Charakterisierung des rekombinanten, bifunktionalen Proteins SDF1-GPVI und dessen Einfluss auf die myokardialen Reparaturmechanismen
(2012) Ziegler, Melanie; Graeve, Lutz
Cardiovascular diseases like myocardial infarction, arteriosclerosis and coronary heart disease are the leading cause of death worldwide. Because of this, development of novel and innovative biopharmaceutical approaches is very important to improve the therapy of cardiovascular diseases. Especially after myocardial infarction, promoting cardiac repair mechanisms is of vital importance to preserve cardiac function and decrease scar size. The chemokine ?stromal cell-dervied factor-1? (SDF-1) plays a crucial role in stem cell homing and is upregulated after myocardial infarction. It is already known that the SDF-1/ CXCR4 axis promotes myocardial repair. In this study we connected SDF-1 with an anchor structure to accumulate this chemokine specifically at the infarcted myocardium. The anchor structure consists of the soluble glycoprotein VI (GPVI). GPVI is the major collagen receptor on platelets and binds to nearly all collagen types and other proteins of the extracellular matrix like fibronectin and vitronectin. Hence, SDF1-GPVI specifically accumulates at the injured tissue and attracts progenitor cells from the blood stream to the lesion site. During the course of this study, the recominant, bifunctional protein SDF1-GPVI, consisting of human SDF-1 and soluble human GPVI, was generated. Subsequently, the functional efficacy of the SDF-1 and GPVI domains were proven by several functional assays and the bifunctionality of SDF1-GPVI was determined by dynamic adhesion in a flow chamber system. Further, in vitro studies showed that SDF1-GPVI triggers chemotaxis of haematopoetic progenitor cells (HPCs), enhances and accelerates endothelial differentiation of HPCs and preserves survival of HPCs. Furthermore, using the ?Chorioallantoic Membrane? (CAM) assay SDF1-GPVI revealed proangiogenic effects in ovo. Prior to in vivo analysis, a pharmacokinetic study showed that SDF1-GPVI has a biological half-life >48 h. After induction of myocardial infarction, treatment with SDF1-GPVI and G-CSF lead to a significantly decrease in infarct size and to a significantly preserved myocardial function 28 days after transient ischemia/reperfusion. Additional positive effects were enhanced homing of GFP-labelled ?bone marrow cells? (BMCs), increased recruitment of CXCR4-positive cells and enhanced neovascularisation in the infarcted myocardium. Therefore, the bifunctional protein SDF1-GPVI bears the potential to serve as a promising biopharmaceutical therapeutic to promote myocardial repair especially after myocardial infarction.
Epidemiology and social determinants of chronic diseases attributed adult mortality and its influence on maternal and young child nutrition in Tigray, 2009-2015: evidence from Kilte Awlaelo- Health and Demographic Surveillance Site
(2023) Abera, Semaw Ferede; Scherbaum, Veronika
In Ethiopia, the burden of disease related to communicable diseases has recently decreased significantly, while morbidity and mortality due to non-communicable diseases (NCDs) have increased. At the same, maternal and child malnutrition remained a major public health problem of Ethiopia. In developing countries, where health insurance is largely unavailable, individual medical conditions can also affect the overall and nutritional well-being of household members. In particular, the occurrence of disease and adult mortality in households can affect the nutritional well-being of the most vulnerable household members, especially lactating mothers and their young children. If the diseases are of chronic nature, which usually are costly and adult household members die from it in the long-term, this can be devastating for the family. The aim of this Ph.D. project was to investigate the epidemiology and social determinants of NCDs-attributed adult mortality, and to examine the association of chronic diseases attributed adult mortality with undernutrition of lactating mothers and their young children in rural population of Kilte Awlaelo-Health and Demographic Surveillance Site (KA-HDSS), Eastern Zone of Tigray, Ethiopia. During the data analysis, causes of death in adults were classified into chronic and non-chronic causes. The category of adult mortality due to chronic diseases refers to all causes that may be characterized by a long duration of illness. This group includes all deaths caused by NCDs and chronic communicable diseases such as tuberculosis and HIV/AIDS. The thesis has three articles, all published in peer-reviewed journals. The first article reports findings on the epidemiology and social-determinants of adult mortality caused by NCDs among 45,982 adult residents of KA-HDSS using population-based longitudinal data collected from 2009 to 2015. The second article tested whether the burden of undernutrition was higher among lactating mothers who were living in households with adult mortality from chronic diseases than among lactating mothers living in households with no adult mortality from chronic diseases. The third article examined whether there was an association between undernutrition of children and adult mortality from chronic diseases. Both longitudinal and cross-sectional data were used in the second and third articles. To our knowledge, this study showed for the first time that adult mortality caused by NCDs varied according household members’ relationship to their household head: extended family and non-family members of the household head had higher hazard of mortality compared to the household heads. In addition, this work can be considered as the first study from a low-income setting to examine whether mortality of an adult household member from chronic diseases is associated with undernutrition of lactating mothers and their young children. The results of the first study indicate a double mortality burden from both communicable diseases and NCDs in the study population. Between 2009 and 2015, the leading causes of NCDs-attributed adult mortality were cardiovascular diseases, cancer and renal failure. Compared to heads of households, extended family and non-family co-residents had an increased hazard of mortality from NCDs. Literacy and younger age were protective factors against adult mortality caused by NCDs. However, the protective role of literacy against adult mortality from NCDs decreased with increasing age. Next, we assessed the level of undernutrition among the lactating mothers and examined its association with household-level occurrence of adult mortality from chronic diseases by controlling the effect of a wide range of epi-demographic and agro-ecological variables. Nearly two-fifths (38%; 95% CI: 36.1, 40.1%) of the mothers were undernourished. We found an increased risk of maternal undernutrition for lactating mothers who were living in households which experienced adult mortality from chronic diseases. In addition, maternal undernutrition was strongly associated with recent history of household-level morbidity, poor health-seeking practice, lack of diverse food crops, and a low index score for housing and environmental factors. In the third article, we determined the burden of undernutrition among children of complementary feeding age (6 to 23 months) and its factors within the context of nutrition-specific and -sensitive drivers of young child undernutrition. Here, mortality from chronic diseases were constructed as a nutrition-specific factor. We found high prevalence of wasting (13.7%; 95% CI: 12.1, 15.5%) and inadequate child dietary diversity (81.3%; 95%CI: 79.2, 83.1%). Adult mortality history from chronic diseases was not associated with young child undernutrition and child dietary diversity. However, child undernutrition was strongly associated with recent history of household-level morbidity, maternal undernutrition, low child dietary diversity, poverty, larger family size, insecure employment of household heads, and living in highland areas. Poor household wealth status and lack of diverse food crops production, particularly in highland areas, were also strongly associated with lower child dietary diversity. Overall, this thesis has shown that an epidemiological transition is ongoing in the surveillance population. Population-based intervention measures are recommended that aim to reduce NCD-related adult mortality by targeting the leading causes of death and focusing on vulnerable population subgroups, such as the extended family and nonfamily household members. In this study, there was no association between the occurrence of chronic diseases attributed adult mortality and young child undernutrition. However, adult mortality from chronic diseases was associated with maternal undernutrition. Our findings appear to call for multi-sectoral interventions, mainly by the agriculture, nutrition and health sectors, to promote nutritional well-being of lactating mothers and their dyads in the long-term.
Food and nutrition security and associated health aspects of Syrian refugee mothers and their offspring : a mixed-method study in Greater Beirut, Lebanon
(2023) Abou-Rizk, Joana; Scherbaum, Veronika
Nutrition during the first 1000 days of life – from conception to two years of age – lays the foundation for optimal health, cognitive and social development, and well-being of children and mothers. Malnutrition and hidden hunger in mothers and their offspring during the perinatal period can have long-lasting and irreversible consequences on human capital and increase the risk to non-communicable diseases among adulthood through intergenerational effects. Since the Arab Spring in 2011, the Syrian humanitarian crisis has escalated to become the world’s largest by the end of 2018, forcing 6.7 million to flee, mainly to neighboring countries. In 2015, Lebanon was the host of more than 1.5 million refugees and displaced persons from Syria, reaching the highest per capita concentration of refugees worldwide. The protracted crisis has increasingly weakened Lebanon, in turn exposing vulnerable groups, especially women of reproductive age and children below five years, to increased risks of inadequate nutrition and health status. To date, there has been a lack of studies among refugees that examine the nutritional and health situation and investigate the underlying and immediate determinants of malnutrition among women of reproductive age and children below five years. Therefore, knowledge gaps regarding the prevalence of anemia and nutritional status of Syrian refugee mothers and children were identified as important research areas in this dissertation. Assessing the food security and mental health of Syrian refugee mothers, examining the dietary intake and infant feeding practices, and investigating their respective determinants and associated risk factors were also important areas of focus. This research project was conducted between July and October 2018 in collaboration with the American University of Beirut in primary healthcare centers in the Greater Beirut area in Lebanon using quantitative and qualitative surveys (mixed-methods survey) among Syrian refugee mothers and their child aged below five years of age. This work comprises a total of three research articles that have been published in peer-reviewed international journals. The first article (Chapter 3) describes the prevalence of anemia and the nutritional status of mothers and children below five years of age and indicates a moderate public heath significance among Syrian refugees in the Greater Beirut area, Lebanon. The existence of the so-called double burden of malnutrition and hidden hunger (micronutrient deficiencies) has been documented, as mothers and children from the same household were affected by undernutrition, overnutrition, and / or anemia. A strong association between maternal and child anemia in the same household and an association between anemia and overweight / obesity among mothers has also been demonstrated. Analysis of the 24-hr dietary recalls of pregnant, lactating, non-pregnant non-lactating mothers revealed inadequate dietary intake and nutrient deficiencies during pregnancy and lactation. The second article (Chapter 4) presents data on the prevalence of food insecurity, low dietary diversity, and poor mental health among Syrian refugee mothers in Greater Beirut, Lebanon. A significant association between food insecurity and low dietary diversity as well as poor mental health status was found. Low household monthly income and a high household crowding index were significantly associated with low dietary diversity and food insecurity. In addition, the results showed that low-income households consumed monotonous diets, characterized by a high consumption of refined starchy staples and grains. The third paper (Chapter 5) focused on the nutritional and health status of infants under six months. Overall, the public heath significance for anemia and wasting was moderate. Inadequate infant feeding practices, such as the intake of pre-lacteal feeding and liquids, were demonstrated in newborns, which in turn contributed to delayed initiation of breastfeeding and low rates of exclusive breastfeeding. Factors supporting infant feeding practices included proper knowledge on maternal nutrition and exclusive breastfeeding and support from healthcare professionals or family during breastfeeding. Identified barriers included cultural practices such as the early introduction of foods, breastmilk substitutes, and giving water or herbal tea to infants under six months of age. Maternal health issues and social factors such as misinformation from family members and violations of the Code of Marketing of Breastmilk Substitutes also affected breastfeeding. A conceptual framework was also developed in this dissertation to provide a comprehensive understanding of the linkages and pathways between the enabling, underlying, and immediate determinants and the nutritional and health outcomes in the context of humanitarian crises. Based on this conceptual framework, three principal pathways were identified to explain the following associations: (1) from the enabling determinants to anemia and nutritional status, (2) from socio-economic status and host country resources to food consumption and diets, and (3) from pre-resettlement experiences and dietary acculturation to food consumption and diets. In addition, the concluding discussion (Chapter 6) presented the role of maternal mental health status and health services and their impact on maternal nutrition and anemia status as well as infant feeding. In summary, this dissertation contributes to the knowledge about the anemia and nutritional status of Syrian refugee women and children as well as on the food security and mental health status of mothers living in an urban setting of a protracted humanitarian crisis in Lebanon. It also provides insights into the emergence of malnutrition among women and children in the context of refugees and shows the pathways between different levels of determinants of nutrition and health. Implications for practice can be drawn from this dissertation, such as the development or strengthening of evidence-based culture-specific nutritional interventions that are targeted to the refugee context. Priorities for future research were also identified, including the need to improve the effectiveness of nutritional interventions in conflict settings.
Gellan gum is a suitable biomaterial for manual and bioprinted setup of long-term stable, functional 3D-adipose tissue models
(2022) Albrecht, Franziska B.; Dolderer, Vera; Nellinger, Svenja; Schmidt, Freia F.; Kluger, Petra J.
Due to its wide-ranging endocrine functions, adipose tissue influences the whole body’s metabolism. Engineering long-term stable and functional human adipose tissue is still challenging due to the limited availability of suitable biomaterials and adequate cell maturation. We used gellan gum (GG) to create manual and bioprinted adipose tissue models because of its similarities to the native extracellular matrix and its easily tunable properties. Gellan gum itself was neither toxic nor monocyte activating. The resulting hydrogels exhibited suitable viscoelastic properties for soft tissues and were stable for 98 days in vitro. Encapsulated human primary adipose-derived stem cells (ASCs) were adipogenically differentiated for 14 days and matured for an additional 84 days. Live-dead staining showed that encapsulated cells stayed viable until day 98, while intracellular lipid staining showed an increase over time and a differentiation rate of 76% between days 28 and 56. After 4 weeks of culture, adipocytes had a univacuolar morphology, expressed perilipin A, and secreted up to 73% more leptin. After bioprinting establishment, we demonstrated that the cells in printed hydrogels had high cell viability and exhibited an adipogenic phenotype and function. In summary, GG-based adipose tissue models show long-term stability and allow ASCs maturation into functional, univacuolar adipocytes.
Increasing post-digestive solubility of curcumin is the most successful strategy to improve its oral bioavailability: A randomized cross-over trial in healthy adults and in vitro bioaccessibility experiments
(2021) Flory, Sandra; Sus, Nadine; Haas, Kathrin; Jehle, Sina; Kienhöfer, Eva; Waehler, Reinhard; Adler, Günther; Venturelli, Sascha; Frank, Jan
Scope: Different mechanistic approaches to improve the low oral bioavailability of curcumin have been developed, but not yet directly compared in humans. Methods and Results: In a randomized, double-blind, cross-over trial with 12 healthy adults, the 24 h pharmacokinetics of a single dose of 207 mg curcumin is compared from the following formulations: native, liposomes, with turmeric oils, with adjuvants (including piperine), submicron-particles, phytosomes, γ-cyclodextrin complexes, and micelles. No free, but only conjugated curcumin is detected in all subjects. Compared to native curcumin, a significant increase in the area under the plasma concentration–time curve is observed for micellar curcumin (57-fold) and the curcumin-γ-cyclodextrin complex (30-fold) only. In vitro digestive stability, solubility, and micellization efficiency of micellar curcumin (100%, 80%, and 55%) and curcumin-γ-cyclodextrin complex (73%, 33%, and 23%) are higher compared to all other formulations (<72%, <8%, and <4%). The transport efficiencies through Caco-2 cell monolayers of curcumin from the digested mixed-micellar fractions did not differ significantly. Conclusion: The improved oral bioavailability of micellar curcumin, and to a lesser extent of γ-cyclodextrin curcumin complexes, appears to be facilitated by increased post-digestive stability and solubility, whereas strategies targeting post-absorptive processes, including inhibition of biotransformation, appear ineffective.
Influence of selenium on pancreatic carcinogenesis and the role of the selenoproteins cytosolic and mitochondrial thioredoxin reductase in the pancreas
(2007) Aichler, Michaela; Graeve, Lutz
Pancreatic ductal adenocarcinoma (PDA) is one of the most aggressive cancers in humans. It is the fourth leading cause of cancer related deaths in Germany and in the United States. Most PDA occurs sporadically, but there are also approximately 5-10% of patients with a family history of pancreatic cancer. The high mortality of PDA is attributed to a lack of early detection methods and poor efficacy in therapies for advanced disease. As an alternative, preventive strategies in individuals with familial pancreatic carcinoma should be considered. Several epidemiological studies showed an inverse correlation between selenium-intake and mortality of certain types of cancer and particularly in gastrointestinal cancers. To this end, in the first part of this study, the influence of selenium as a preventive nutritional additive was investigated in a genetically defined pancreatic cancer mouse model, the EL-TGFatg/+;p53+/- mouse strain. As a major finding, the differentiation grade of the pancreatic carcinomas was heavily influenced by the selenium status. In the selenium-deficient group there were more non-differentiated pancreatic carcinomas than in the selenium-adequate group, which highlighted the implication of selenium or selenoproteins in tumour differentiation. Unexpectedly, however, there was no protective effect of selenium on total or pancreatic tumour latency. Within the selenoproteins, the thioredoxin reductases are strong candidates which may influence cell death and differentiation in pancreatic carcinogenesis. Their function is generally associated with tumour proliferation and also linked to the activation of the tumour suppressor p53. Consequently, the role of the thioredoxin reductases in the pancreas was studied in the second part of this thesis. The enzymatic activity of cytosolic (TXNRD1) and mitochondrial (TXNRD2) thioredoxin reductase in the pancreas and other organs was determined in relation to the selenium-status. TXNRD1 activity in the pancreas was moderate and decreased under selenium deficiency. TXNRD2, instead, showed very high pancreatic activity in relation to other organs and its activity was even increased under selenium-deficiency emphasising its special role in this organ. To further investigate the function of Txnrd1 and Txnrd2 in the pancreas, tissue-specific knockout mice were created and characterized. The Txnrd1 knockout mice did not show an overt phenotype. Interestingly although, pancreatic acinus cells in one year old mice showed a disturbed rough endoplasmic reticulum and alterations in serum amylase and lipase. These mice also had an impaired glucose tolerance. The pancreas of Txnrd2 knockout mice showed severe chronic pancreatitis and pancreatic atrophy at the end of an observation period of one year. The progressive pathogenic process started with mild pancreatitis, developing spontaneously at an age of four weeks. The chronic stage was characterized by the formation of different types of acinar-to-ductal metaplastic lesions, which could be classified in part as early precursor lesions of pancreatic carcinomas. The endocrine pancreas was not affected. The pancreas-specific Txnrd2 knockout mouse strain is the first genetically modified mouse model spontaneously developing acute and chronic pancreatitis. This strain constitutes a unique and powerful tool to model pancreatic pathogenesis, especially the yet unresolved process of transformation from inflammatory to malignant disease.
Mangelernährung bei Tumorpatienten unter Chemotherapie : Anwendung und Weiterentwicklung eines computergestützten Programmes zur Erfassung und Vorhersage des Ernährungsstatus onkologischer Patienten
(2012) Renger, Sebastian; Biesalski, Hans-Konrad
Malnutrition is a serious problem in the health care of cancer in- and outpatients. Especially for outpatients there is little information on their nutritional status available, because nutritional screenings are not often used, although there is plenty of them accessible. The workgroup of Professor Biesalski developed a software, called oncoMAT, to calculate the current and the prospective nutritional status of tumour patients. Patient data of cancer patients from Tübingen and Freiburg were collected and analysed to test the program. For comparison the gold standard SGA (Suvjective Global Assessment) was used. Anthropometry, BIA, blood analysis and patient questioning about adverse events were used to evaluate the nutritional status as well. Results were checked for specificity and sensitivity. The Risk-Score statements were evaluated considering different model-conditions. To calculate the prognostic score, patient- and illnessrelated parameters were proved by a variance analysis and a multiple linear regression.
Nutrition and health aspects of mothers and their infants in Bukavu region, Democratic Republic of the Congo : a follow-up study with cross-sectional analyses and nutrition interventions
(2024) Beitze, Damaris Elisabeth; Scherbaum, Veronika
Hintergrund: Mangelernährung in verschiedenen Ausprägungen ist eine Herausforderung für die Bevölkerungsgesundheit in der Demokratischen Republik Kongo, einem Land, das von politischer Instabilität, Gewalt, Nahrungsmittelunsicherheit und Armut geprägt ist. Vor allem verborgener Hunger und Anämie machen einen großen Teil davon aus. Unzureichende Ernährung während der ersten 1000 Lebenstage beeinträchtigt die Gesundheit und Entwicklung eines Kindes kurz- und langfristig. Das Ernährungsverhalten der Mütter spielt sowohl für ihren eigenen Ernährungszustand als auch für den ihrer Kinder eine wichtige Rolle, insbesondere während dieser sensiblen Phase. Der Ernährungszustand und das Ernährungsverhalten können durch vielfältige Faktoren auf verschiedenen Ebenen beeinflusst werden. Diese müssen untersucht und berücksichtigt werden, um zielführende Interventionen zu gestalten. Zielsetzung: Diese Dissertation hatte zum Ziel, den Ernährungsstatus, insbesondere Anämie, stillender Frauen und ihrer Säuglinge zu untersuchen, ebenso wie damit assoziierte Faktoren. Des Weiteren sollte der Einfluss von Ernährungsschulungen und Lipid-basierten Nährstoffsupplementen auf Anämie, Ernährungswissen und Ernährungsverhalten von unter- und übergewichtigen Müttern ermittelt werden. Methoden: Eine Follow-up-Studie mit Querschnittserhebungen und inkludierter Interventionsstudie wurde mit 471 stillenden Müttern und ihren Säuglingen in der Region von Bukavu, Demokratische Republik Kongo von Dezember 2017 bis Juni 2019 durchgeführt. Mutter-Kind-Paare wurden nach der Entbindung in einem von drei Krankenhäusern der Studie (zwei davon semi-urban und eines im ländlichen Gebiet) in der ersten Woche postpartum rekrutiert. Die erste Datenerhebung beinhaltete anthropometrische Messungen der Mütter und Neugeborenen sowie ein strukturiertes Interview zu sozio-demographischen Faktoren und Ernährungsaspekten während der Schwangerschaft. Folgeerhebungen, die 3-6 und 6-9 Monate nach der Geburt stattfanden, umfassten die Messung von anthropometrischen Parametern und der Hämoglobin-Konzentration (Hb) von Müttern und ihren Säuglingen, ein 24-Stunden Ernährungsprotokoll der Mütter sowie ein strukturiertes Interview zu Ernährungswissen und -verhalten. Die randomisierte kontrollierte Interventionsstudie fand zwischen diesen beiden Folgeerhebungen statt. Vor der Intervention wurden die Mütter anhand ihres mittleren Oberarmumfangs (MUAC) in niedrigen (≥ 21 und < 25 cm), normalen (≥ 25 und < 28 cm) und hohen MUAC (≥ 28 cm) eingestuft. Anschließend wurden sie zufällig den folgenden Interventions- und Kontrollgruppen zugeteilt: niedriger MUAC – Ernährungsschulung; niedriger MUAC – Supplement; niedriger MUAC – Kontrolle; mittlerer MUAC – Kontrolle; hoher MUAC – Ernährungsschulung; hoher MUAC – Kontrolle. Über drei Monate erhielten Mütter mit Ernährungsschulungen vier theoretische und zwei praktische Einheiten zu ausgewogener Ernährung, Eisen, Vitamin A und Nährstoffmängeln. Mütter in der Supplement-Gruppe erhielten ein tägliches Lipid-basiertes Nährstoffsupplement. Für 416 Mütter und Säuglinge waren Daten vor und nach der Intervention vorhanden. Ergebnisse: Die Studie zeigte die Koexistenz verschiedener Formen von Mangelernährung in der Studienpopulation. Ernährungs- und Gesundheitsaspekte unterschieden sich zwischen den semiurbanen und ländlichen Gegenden. Das Erhalten von Leistungen während der Schwangerschaftsbetreuung (Malaria-Medikamente, Entwurmung, Supplemente, Ernährungsinformationen durch Gesundheitspersonal) und das Wissen zu sowie die Umsetzung von Familienplanung waren im ländlichen Gebiet geringer als im semi-urbanen Gebiet, ebenso anthropometrische Parameter wie der mütterliche MUAC und das Geburtsgewicht. Eine multiple lineare Regression ergab zunehmenden mütterlichen MUAC, Alter und Gestationsalter als positive Einflussfaktoren auf das Geburtsgewicht, während die ländliche Lage, eine erstgebärende Mutter, eine Tätigkeit der Mutter in der Landwirtschaft und das weibliche Geschlecht des Neugeborenen negative Prädiktoren des Geburtsgewichts waren. Die Anämieraten 3-6 Monate nach der Geburt waren mit 28,2 % bei den Müttern von mittlerer Relevanz für Bevölkerungsgesundheit, lagen bei den Säuglingen mit 74,3 % jedoch im schwerwiegenden Bereich. Sowohl das mütterliche Ernährungswissen als auch ihre Ernährungsvielfalt waren gering ausgeprägt. Im Median hatten die Mütter ein Wissen von 0,39 in einem möglichen Bereich von 0 bis 1 und eine Ernährungsvielfalt von 3,0 (möglicher Bereich 0-10). Ernährungswissen und mütterlicher Hb waren leicht positiv korreliert, aber es bestanden keine signifikanten Korrelationen der Ernährungsvielfalt mit einem dieser beiden Parameter. Geschmack (68,1 %), Aussehen (42,5 %), die Wirkung von Lebensmitteln auf die Gesundheit (29,0 %) und Verfügbarkeit (25,6 %) waren häufige Kriterien der Lebensmittelauswahl. Nach der Intervention hatten Mütter, die Ernährungsschulungen erhalten hatten, ein signifikant höheres Ernährungswissen als diejenigen ohne Schulungen, aber keine verbesserte Ernährungsvielfalt. Außerdem modifizierten mehr Mütter mit Schulungen die Beikost für ihr Kind als die anderen Mütter, häufig im Zusammenhang mit Inhalten der Ernährungsschulungen. Weder der mütterliche Hb nach der Intervention noch die Hb-Entwicklung über die Interventionsphase unterschieden sich signifikant zwischen den sechs Interventions- und Kontrollgruppen. Allerdings war der Anteil an Müttern mit einer Verbesserung des Hb in den Gruppen mit Ernährungsschulungen größer, wenn auch nicht statistisch signifikant. Bei Betrachtung ausschließlich der Frauen, die zu Beginn der Intervention an Anämie litten, zeigte sich eine größere Zunahme des Hb in den Gruppen, die entweder Schulungen oder Supplemente erhielten, allerdings nicht statistisch signifikant. Schlussfolgerungen: Der Ernährungsstatus stillender Frauen und ihrer Säuglinge im Studiengebiet war mangelhaft. Verschiedene Faktoren, die die Mangelernährung befördern könnten, wurden identifiziert: Unzureichende Nahrungsaufnahme und eingeschränkte Leistungen in der primären Gesundheitsversorgung können den Ernährungsstatus beeinflussen. Zu ihren möglichen, vielschichtigen Determinanten gehören geringes Ernährungswissen, die ländliche Gegend und Nahrungsmittelunsicherheit, aber auch persönliche Präferenzen. Um den Ernährungszustand effektiv zu verbessern, müssen Ernährungsinterventionen diese verschiedenen Einflussfaktoren der Nahrungsaufnahme adressieren. Ernährungsschulungen und Lipid-basierte Nährstoffsupplemente könnten einen positiven Effekt haben, vor allem bei Müttern mit Anämie. Sie sollten weiter untersucht werden. Es wird empfohlen, das Bewusstsein und die Qualifikation von Gesundheitspersonal in der primären Gesundheitsversorgung hinsichtlich Ernährung zu stärken und praktische Elemente in Maßnahmen mit Ernährungsschulungen zu integrieren.
Nutrition-related knowledge, attitudes, practices, and anemia status of lactating mothers in Bukavu, Democratic Republic of the Congo - A cross-sectional analysis
(2024) Beitze, Damaris Elisabeth; Kavira Malengera, Céline; Barhwamire Kabesha, Theophile; Scherbaum, Veronika
Maternal nutrition is impacted by personal and environmental factors including dietary intake, knowledge, food availability, and affordability. This cross-sectional analysis aimed to evaluate nutrition-related knowledge, attitudes, practices, and associations with hemoglobin concentration among lactating mothers in the Bukavu region, Democratic Republic of the Congo. In 444 lactating mothers, nutrition-related knowledge and practice were assessed by questionnaires and translated into knowledge and practice scores ranging from 0 to 1, attitudes and drivers of food choice were assessed, the Dietary Diversity Score (DDS) was assessed with 24 h dietary recalls in a potential range from 0 to 10, and hemoglobin (Hb) was measured in mothers and their infants. Anemia prevalence was 28.2% among mothers and 74.3% among infants aged 3–8 months. Nutritional knowledge and practice were limited (the median total knowledge score was 0.39, median DDS was 3.0). While there were slight positive correlations between knowledge and maternal Hb, DDS did not significantly correlate with either knowledge or Hb. Although half of the mothers stated a perception about their own susceptibility to anemia or vitamin A deficiency (56.4%, 47.4%), less than half of those could justify their estimation (40.9%, 44.2%). Taste (68.1%), appearance (42.5%), availability (29.0%), and health effects (25.6%) were important drivers of food choice. In conclusion, interventions on the different influencing factors including nutrition education strategies are needed.
Nutritional status and its impact on outcome in patients undergoing allogeneic haematopoietic cell transplantation and an experimental trial to improve the supply of a specific micronutrient
(2012) Urbain, Paul; Biesalski, Hans-Konrad
The first two studies investigated the course of the nutritional status in patients un-dergoing allogeneic haematopoietic cell transplantation (alloHCT) and the validity of nutritional markers as independent risk factors for outcome. In line with others, we detected an overall good nutritional status before alloHCT by employing quick screening tools such as BMI and the SGA questionnaire for identifying malnutrition. However, upon closer inspection, we observed unintentional weight loss previous to alloHCT to be a frequent condition, detecting many more underweight patients using age- and gender-specific BMI classification and overall low bioelectrical impedance phase angle values at admission. Deterioration in nutritional status during the early post-transplant period was significant in the cohort. Furthermore, we identified ano-rexic patients and those with clinically-relevant aGVHD (≥°II) to have an increased risk for a decline in nutritional status during early rehabilitation. In addition, it could be demonstrated for the first time that the pretransplant phase angle (≤25th percen-tile) used as a standardised value was an independent predictor for 2-year overall survival, non-relapse mortality and progression-free survival. BMI adjusted for age and gender emerged as an independent risk factor for OS and NRM. Both of these nutritional markers performed better than numerous generally-accepted risk factors, and they were the only significant prognostic values for outcome in this cohort be-sides HLA-C compatibility, donor and remission status. In addition, these two nutri-tional markers are theoretically modifiable during the often lengthy treatment period before transplantation. Further investigation is necessary to demonstrate whether or not the phase angle can be increased by strategies that enhance muscle mass via physical training together with nutritional support, and whether it can prevent dete-rioration in nutritional status and lead to beneficial effects on outcome after alloHCT. The third study investigated the association between AOX status (α-tocopherol, ascorbic acid and ß-carotene) in buccal mucosa cells (BMC) or plasma and the risk of developing oral mucositis (OM) after conditioning chemotherapy. We observed no significant differences in baseline AOX concentrations in plasma or BMC among the different OM groups (no or mild, ulcerative and severe OM), revealing that no single AOX has predictive value for the incidence or severity of OM after conditioning chemotherapy. However, patients with an overall good plasma AOX status tended to require a shorter duration of parenteral nutrition, which is a relevant clinical and economic marker for OM treatment compared to patients with at least one plasma AOX beneath the normal range. These findings may indicate that an intact antioxidative network is more relevant than any one AOX for lowering the OM risk. Future studies should consider both the exogenous- and endogenous AOX systems. The fourth study revealed a generally low serum 25-hydroxyvitamin D [25(OH)D3] status in these patients at admission. Furthermore, their 25(OH)D3 status remained low during the early post-transplant period, showing a trend towards further deterio-ration, especially in patients with corticosteroid-treated aGVHD. In addition, we con-ducted a detailed investigation of the impact of well-known influencing factors on baseline serum 25(OH)D3 status, revealing only higher body fat mass to be an inde-pendent risk factor for reduced baseline status. In fact the most important influenc-ing factors, namely dietary factors and season, revealed no detectable impact, most probably due to inadequate oral intake, prolonged disease history, and hospitalisa-tion. In conclusion, these results provide a clear rationale for the use at least of vitamin D-containing multivitamin preparations in standard multivitamin prescrip-tions, and for the monitoring of vitamin D status at regular intervals from the date of diagnosis. The fifth study was a randomised controlled trial revealing for the first time in humans that the bioavailability of vitamin D2 from vitamin D2-enhanced button mushrooms via UV-B irradiation is effective in improving vitamin D status in young, healthy adults and not different than a vitamin D2 supplement. The vitamin D2 enhancement of mushrooms boosts their nutraceutical value by creating both an abundant and excellent source of vitamin D2 that opens up new opportunities in fighting widespread vitamin D deficiency.
Probiotic bacteria enhance the antibacterial barrier of enterocytes: insights into their mechanism of action
(2007) Schlee, Miriam; Bode, Christiane
In the healthy intestine there is a stable balance of luminal bacteria and host factors to prevent infections or inflammatory bowel diseases (IBD). A complex network of environmental, genetic, and immunoregulatory factors may precipitate the onset of ulcerative colitis (UC) and Crohn's disease (CD), the primary manifestations of inflammatory bowel disease (IBD). It is currently believed that IBD results from an aberrant immune response of the intestinal mucosa towards the normal commensal bacterial flora. Alternatively, a primary defect in the mucosal barrier might permit bacterial invasion and trigger inflammation. In our research group the hypothesis was proposed that the defective barrier in Crohn´s disease may be due to a lack of defensins which form a chemical barrier against luminal bacteria. A major gut defensin is the human beta defensin-2 (hBD-2) which is an inducible antimicrobial peptide synthesized and secreted by the epithelium to counteract bacterial adherence and invasion. Proinflammatory cytokines, as well as certain bacterial strains, have been identified as potent endogenous inducers. In recent studies, Fellermann et al demonstrated that the defective expression of hBD-2 which was measured in the gut mucosa of patients with Crohn´s disease was due to a reduced copy number of the hBD-2 gene. In patients with ulcerative colitis beta-defensin expression is low in the colon during remission, but readily inducible during inflammation. Probiotic bacteria might act beneficially in the human gut by inducing the expression of defensins and thereby reinforcing the mucosal barrier. Recently, our group has been the first to describe hBD-2 induction by the probiotic strain E. coli Nissle (Mutaflor®) which is an effective treatment for ulcerative colitis during remission. The aim of the present work was to determine the underlying molecular mechanisms. We determined a time- and dose-dependent expression pattern of hBD-2 in Caco-2 cells upon stimulation with IL-1 beta;, E. coli Nissle culture supernatant and diverse other probiotic strains. We further investigated the transcriptional regulation of hBD-2 expression mediated by probiotics. The hBD-2 promoter contains several elements known to be involved in transcriptional upregulation such as the NF-kappa B element, which is believed to be one of the main regulators of the hBD-2 gene expression. However, for certain signals, the expression of the hBD-2 gene has been reported to depend on the activation of a second transcription factor, such as AP-1. Most importantly, E. coli Nissle was shown to shed or secrete factors, contained in the bacterial supernatant, which were sufficient to trigger activation of NF-kappa B and AP-1 and to induce hBD-2. Our results indicated further that the supernatant-induced activation of the MAP kinase pathways ERK½, JNK, and p38 may be directly responsible for the probiotic supernatant-induced activation of the transcription factors AP-1 and NF-kappa B and subsequent synthesis of hBD-2. A further aim of the present study was to identify and isolate the bacterial components which are responsible for E. coli Nissle mediated hBD-2 induction. As E. coli Nissle culture supernatant was found to be a more potent stimulant than the bacterial pellet, we investigated the characteristics of the unknown soluble or shed molecules in the bacterial culture media. The first analysis revealed the factor as a heat resistant and proteinase sensitive molecule. Both, E. coli Nissle specific lipopolysaccharide (LPS) and bacterial DNA, which might contain immunostimulatory DNA motifs, failed to trigger hBD-2 expression. Based on the knowledge of the surface composition several E. coli Nissle deletion mutants were constructed and tested for their ability to induce hBD-2 expression in Caco-2 cells. Deletion mutants for flagellin, the flagella filament protein, specifically exhibited an impaired immunostimulatory capacity. Reinsertion of the flagellin gene restored the induction capacity to normal levels. Next, we isolated flagellins from different bacteria strains (Salmonella enterica serovar Enteritidis, E. coli ATCC 25922, E. coli Nissle and the uropathogenic E. coli strain CFT073 Delta hly, whose genome structure resembles closely that of E. coli Nissle). In the Western blot anti-H1 flagellin displayed immunoreactivity against the different types of flagellins, due to the highly conserved central region of the flagellin filament structure. Incubation of Caco-2 cells with isolated E. coli Nissle flagellin (molecular size 60.81 kDa) induced hBD-2 promoter activation in a dose-dependent manner. The induction of hBD-2 expression by flagellin was confirmed with a positive control (Salmonella flagellin). Interestingly, the serotype-identical CFT073 Delta hly flagellin expressed only moderate hBD-2 inducing ability compared to E. coli Nissle flagellin. Thus, differences in extracellular matrix e.g. the glycosilation degree might underlie the differentially modulated hBD-2 response of Caco-2 cells by the two flagellins. H1 flagellin antiserum abrogated hBD-2 expression induced by flagellin as well as E. coli Nissle supernatant, confirming that flagellin is the major stimulatory factor of E. coli Nissle. In conclusion, flagellin of E. coli Nissle provides reinforcement of mucosal antimicrobial function, apparently without inducing inflammation. This might explain the beneficial effects of E. coli Nissle on remission maintenance in ulcerative colitis. In patients with Crohn´s disease there is evidence against a therapeutic effect of probiotics and this may be explained by a defective defensin system. Future investigations about strain-specific beneficial functions might contribute to the therapeutic application of science-based probiotic products.
Ready-to-Use Food (RUF) from composite flour of local commodities in Banten Province, Indonesia for prevention and rehabilitation of malnutrition in children under five
(2021) Fetriyuna, Fetriyuna; Biesalski, Hans-Konrad
Indonesia faces a serious problem of malnutrition especially stunting and underweight caused by micronutrient deficiencies. The high prevalence of undernutrition was also found in Banten Province, Java Island, the most populated island in Indonesia. The Indonesian Demographic and Health Survey (DHS) in 2012 reported that of about 24.5 million children under five years of old, approximately 37% and 12% of them were stunted and wasted. Furthermore, based on the Basic Health Survey (Riskesdas) in 2013 and 2018, the prevalence of stunting in children under five years old was 37.2 % and 30.8%, while the proportion of underweight children was 19.6% and 17.7%. The undernourished children have an increased mortality rate, risk of illness and infections, cognitive shortages, delayed development, and poor school performance. Ready-to-use food (RUF) is a kind of food easily consumed without much preparation and can be made using various techniques for targeted consumers. RUF can be produced using locally available food resources, which may be affordable for most people suffering from undernutrition. To improve and accomplish the nutrient content of RUF to meet the standard for rehabilitation food for malnutrition, the combination of various food resources might enhance the nutritional composition. This nutritious formulation must have the following attributes: good nutritional quality in macro and micronutrient content, highly palatable taste, consistency, and texture suitable for feeding to children, no additional processing required prior to feeding, product stability, long shelf life, and readily available ingredients. This research was divided into three main objectives. The first objective was a baseline assessment of the nutritional condition of the target group of children below five years old. The second section was RUF biscuit product development. The third objective was to investigate the nutritional outcomes of the field study in Banten Indonesia, particularly in WHZ and weight after the RUF provision and weight gain of the children and acceptability. The RUF biscuit was made from the composite flour of local food resources available in Banten province Indonesia which are still underutilized. The result of nutrition content analysis in local food resources showed that the foods have a high nutritional composition as a source of macronutrients and micronutrients (vitamins and minerals). Due to poor handling of post-harvest and processing into the intermediate product (flour), some vitamins were lost during the process. Based on the baseline assessment in 2017, of the 105 children, 4.8% and 11.4% of them were wasted and overweight-obese, while 40% and 23.8% of the children were stunted and underweight. Based on the mid-upper-arm circumference, 16.1% of children were categorized as the risk of chronic energy deficiency (CED). In addition, it was found that most of the children have insufficient intake of protein, Vitamin A, Iron, and Zinc. Twelve recipes developed using the combination of local food resources showed the macronutrient composition that met the requirement for the treatment of Moderate Acute Malnutrition (MAM) children, but not for micronutrient (vitamin and minerals). Five recipes (recipes 3, 4, 7, 11, and 12) were selected based on nutritional composition and sensory evaluation. The selected recipes were continued to further research of acceptability study in Banten, Indonesia. Before the acceptability study in the field, the micronutrient composition of the recipes chosen was improved according to the MAM treatment recommendation. It fortified the RUF with micronutrient premix. The micronutrient stability test was performed to analyze the loss due to baking. Around 15-28% of the vitamins (A, B1, B2, and E) were lost after baking, which was slightly lower than the other published articles, perhaps due to the short process of baking (15 minutes). Furthermore, the micronutrient sources were from the vitamin-mineral premix with higher stability than that from foods. Minerals content was stable during the baking process. Before the acceptability study started, five fortified cookie recipes were tested to select two for the acceptance and intervention pilot study. Most of the children in the acceptance study reported that they accepted and liked the RUF cookies. The consumption of RUF biscuits for two weeks led to an improvement in the nutritional status: Reduction of severe wasting (WHZ) from 5.7% to 4.3% and of severe underweight (WAZ) from 8.6% to 4.3%. There was no difference in terms of stunting (HAZ). Thus, it has been shown that the developed RUF biscuits have the potential to reduce malnutrition in the under 5-year-olds in the target area.
Strain-resolved analysis of the human intestinal microbiota
(2022) Podlesny, Daniel; Fricke, Florian W.
The gut microbiota is ascribed a crucial role in human health, particularly in regulating immune and inflammatory responses, which is why it is being associated with a wide range of diseases, including obesity, diabetes, and cancer. Nonetheless, fundamental ecological questions of microbiome establishment, stability and resilience, as well as its transmission across hosts and generations remain incompletely understood, partly due to the lack of methods for high-resolution microbiome profiling. New insights in this field can therefore directly contribute to the development of bacterial and microbiota-based therapies. This work introduces SameStr, a novel bioinformatic program for strain-resolved metagenomics that allows for the specific tracking of microbes across samples, enabling the detection and quantification of microbial transmission and persistence, as well as the observation of direct strain competition. Deployed across cohorts to process over 4200 metagenomes, SameStr enabled analysis of the microbiome with unprecedented phylogenetic resolution. The data included both publicly available metagenomes and sequence data generated in collaboration with our research partners, and was examined using multivariate statistics and machine learning frameworks. First, the establishment and development of the neonatal microbiota was studied, revealing a birth mode-dependent vertical transmission of the maternal microbiota. The microbiota of neonates born by cesarean section was characterized by increased relative abundance of oxygen-tolerant and atypical organisms and showed signs of a delayed establishment of a strictly anaerobic gut environment in these children. Such birth mode-dependent differences diminished over time, yet were measurable within the first two years of life. Furthermore, strain analysis verified the transmission and colonization of parental microbes, which indicated a possible lifelong colonization by microbes from selected species. The temporal persistence of microbes was also characterized in healthy adults, revealing similar taxonomy-dependent patterns of stability. For some species, persistence has been demonstrated both in children and in adults over a period of at least two years. These species are known for their capability to metabolize host-derived glycans found both in breastmilk and intestinal mucus, pointing to a potential strategy for effective cross-generational microbiota transmission, and warranting additional research to assess the implications of their disturbed transfer for long-term health. Since their specificity allows assignment to individual hosts, fingerprints of individual microbial strains offer the potential to be used in forensics and data quality control applications. Finally, to gain new insights into the microbiota dynamics during Fecal Microbiota Transplantation (FMT), microbial strain transmission was analyzed in the context of a diverse set of patient, microbiome, and clinical conditions. In the analyzed studies, FMT was used for the experimental treatment of a variety of diseases, including colonization with drug-resistant and pathogenic microbes, metabolic and inflammatory bowel diseases, and as an adjunct to the immunotherapeutic treatment of cancer. Analyses uncovered what appear to be the universal drivers of post-FMT microbiota assembly, including clinical and ecological factors that are important for successful transplantation of donor strains. In particular, the relevance of the microbiota dysbiosis of the recipient was emphasized, which was inducible by pre-treating the patient with antibiotics or laxatives. Presumably, this can open up ecological niches in the patients intestines, which favors colonization with donor strains. Colonization rates did not play a role for the treatment success of recurrent C. difficile infections and inflammatory bowel disease, but indicated a trend associated with an improved immune response in cancer patients. Concerningly, the transfer of an atypical and potentially pro-inflammatory microbial community from one donor was also observed, calling for further investigations into the immediate and long-term clinical consequences of FMT. These analyses demonstrate the advantages of a strain-based microbiome analysis. Due to the achieved methodological accuracy, strain-resolved microbial dynamics could be precisely disentangled when comparing longitudinal samples from healthy adults as well as parent-child and patient-donor pairs. This revealed taxonomic, clinical, and ecological factors that are critical to microbiome assembly, including microbial transmission, persistence, and competition. Together, these findings lay the groundwork for future developments of precision personalized microbiota modulation therapies.
Transepitheliale Stimulation humaner Leukozyten durch Bakterien und ihre Oberflächenbestandteile
(2007) Bäuerlein, Annette; Parlesak, Alexandr
Background: The intestinal mucosa plays an important role in the discrimination of immune response between pathogenic and non-pathogenic bacteria as well as in mediating the systemic immunity. To adress the question whether probiotic, commensal, pathogenic germs and bacteria of food origin as well as their membrane components modify the immune response of the intestinal mucosa, we co-cultivated enterocyte-like CaCo-2 cells with human blood leucocytes in transwell cultures. Of further interest was the sequence of enteroxyte-leukocyte activation. Methods: PBMC (Peripheral blood mononuclear cells) were stimulated transepithelially in CaCo-2/PBMC co-cultures and directly challenged with probiotic, commensal, enteropathogenic and food-originating bacteria as well as with membrane components of grampositive and gramnegative bacteria. The expression of inflammatory cytokines (TNF-α, IL-8, IL-6, IL-10 and IFN-γ) was studied by enzyme linked immunosorbant assay (ELISA). The ratio of IL-8/18S mRNA was detected using quantitative reverse transcription polymerase chain reaction (qRT PCR). The permeation of endotoxin was quantified via Limulus amobocyte (LAL) assay and the integrity of the CaC-2 cell monolayer was detected via fluorescein-dextran and transepithelial electric resistance (TEER). Results: Grampositive bacteria did not activate immunocompetent cells in leukocyte-enterocyte co-cultures whereas a stimulation with the gramnegative probiotic E. coli Nissle resulted in higher expressions of TNF-α, IL-8, IL-6, IL-10 and IFN-γ than stimulation with the enteropathogenic E. coli (EPEC). The feature ?probiotic? results not necessarily in an enhanced production of inflammatory cytokines. Differences in epithelial permeability were not necessarily associated with an enhanced activation of immunocompetent cells. There was no activation of immunocompetent cells after direct or transepithelial stimulation with lipoteichoic acid (LTA) of E. faecalis. In contrast, endotoxin depending on its structure was a very potent (E. coli K12, E. coli Nissle, S. Typhimurium) or a moderately potent (B. vulgatus, B. vulgatus MPK) inducer of an inflammatory cytokine response. A neutralisation of endotoxin permeating into the basolateral compartment with Polymyxin B and Colisin resulted in a nearly total inhibition of inflammatory response. Furthermore, directly stimulated PBMC with comparable amounts of the permeating endotoxin in CaCo-2/PBMC co-cultures showed the same activation status as transepithelially stimulated cells. The probiotic, nonstimulating bacteria (Lb. rhamnosus GG, B. vulgatus, B. bifidum) were not able to reduce the E. coli K12 induced TNF-α, IL-8, IL-6, IL-10 and IFN-γ production. A co-stimulation of LPS from E. coli K12 (1 µg/ml) with non-stimulating endotoxins (B. vulgatus and B. vulgatus MPK) 100 µg/ml tended to reduce cytokine expression. Conclusion: These results show that the attribute ?probiotic?does not result in an obligatory activation of immunocompetent cells. The ability to stimulate immunocompetent cells is preferentially dependent on the presence of endotoxin, regarding the structure which is responsible for the stimulating capacity and is not mediated by enterocytes in first line. Activation of the basolaterally located lymphocytes occurs via permeating endotoxin. The permeability of the intestinal epithelial layer is only relevant when permeating endotoxin is able to stimulate immunocompetent cells to due its structural features.

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