Project description:Among the diverse forms of symbioses, facultative nutritional mutualism forged by the host and its resident gut microbiota permits the symbiont to adapt to the changing nutritional environment during the host’s life time. The horizontally acquired gut bacteria in Drosophila are a perfect example of nutritional mutualists. Here, we study the Lactobacillus plantarum (Lp WJL) infection effect in the Drosophila Genetic Reference Panel (DGRP) collection in context of larvae raised in chronic undernutrtion.
Project description:The indigenous human gut microbiota is a major contributor to the human superorganism with established roles in modulating nutritional status, immunity, and systemic health including diabetes and obesity. The complexity of the gut microbiota consisting of over 1012 residents and approximately 1000 species has thus far eluded systematic analyses of the precise effects of individual microbial residents on human health. In contrast, health benefits have been shown upon ingestion of certain so-called probiotic Lactobacillus strains in food products and nutritional supplements, thereby providing a unique opportunity to study the global responses of a gut-adapted microorganism in the human gut and to identify the molecular mechanisms underlying microbial modulation of intestinal physiology, which might involve alterations in the intestinal physico-chemical environment, modifications in the gut microbiota, and/or direct interaction with mucosal epithelia and immune cells. Here we show by transcriptome analysis using DNA microarrays that the established probiotic bacterium, L. plantarum 299v, adapts its metabolic capacity in the human digestive tract for carbohydrate acquisition and expression of exo-polysaccharide and proteinaceous cell surface compounds. This report constitutes the first application of global gene expression profiling of a gut-adapted commensal microorganism in the human gut. Comparisons of the transcript profiles to those obtained for L. plantarum WCFS1 in germ-free mice revealed conserved L. plantarum responses indicative of a core transcriptome expressed in the mammalian gut and provide new molecular targets for determining microbial-host interactions affecting human health. Hybridization of the samples against a common reference of gDNA isolated from L. plantarum 299v
Project description:Feed additives aiming to improve gastrointestinal health are frequently supplied to piglets after weaning but might be more effective when administered before weaning. In this period, feed additives can either be administered directly to neonates, or indirectly via sow’s feed. It is yet unknown what the effect of the administration route is on gut functionality and health. Therefore, we compared the effect of different dietary interventions on gut functionality after maternal administration (lactation feed) to the neonatal administration route (oral gavage). These feed interventions included medium chain fatty acids (MCFA), beta-glucans (BG), and galacto-oligosaccharides (GOS). We measured intestinal gene expression and microbiota composition after birth (d1) and after weaning (d31). Our results show that the type of intervention and the administration route influence gut functionality (microbiome and gene expression profiles). MCFA administration led to a more differentially orchestrated response when comparing the neonatal and maternal administration route then the other two additives, indicating the route of administration of the feed interventions is determinative for the outcome. This implies that for each nutritional intervention in early life of a pig the optimal route of administration needs to be determined.
Project description:Nutritional supplementation is emerging as a promising strategy to support the clinical management of early Alzheimer’s disease (AD), partly through modulation of the intestinal microbiome via the microbiota–gut–brain axis. This study investigated the impact of Fortasyn Connect (Souvenaid®), a multinutrient formulation, on the gut microbiota using a dual approach: i) a dynamic gastrointestinal simulator (simgi®) inoculated with fecal samples from AD patients, and ii) an observational study involving early-stage AD patients (n = 22) receiving or not the supplement. The in vitro model provided a host-independent assessment of microbiota responses, revealing increased Bifidobacterium and Lactobacillus levels, along with enhanced short-chain fatty acid (SCFA) production. In patients, supplementation was associated with higher fecal abundance of Bifidobacterium and Christensenellaceae, reduced inflammatory markers (calprotectin and myeloperoxidase), and elevated butyrate levels. Fecal lipidomic and proteomic analyses indicated improved lipid digestion, increased secretory IgA, and modulation of host proteins related to gut–brain homeostasis. Systemically, higher circulating levels of iron, folate, and vitamin B12 were also observed. This study demonstrates that multinutrient supplementation such as Fortasyn Connect can beneficially modulate the gut ecosystem and immune–metabolic pathways in early AD, targeting disease-relevant mechanisms through the gut–brain axis in the context of aging.
Project description:The indigenous human gut microbiota is a major contributor to the human superorganism with established roles in modulating nutritional status, immunity, and systemic health including diabetes and obesity. The complexity of the gut microbiota consisting of over 1012 residents and approximately 1000 species has thus far eluded systematic analyses of the precise effects of individual microbial residents on human health. In contrast, health benefits have been shown upon ingestion of certain so-called probiotic Lactobacillus strains in food products and nutritional supplements, thereby providing a unique opportunity to study the global responses of a gut-adapted microorganism in the human gut and to identify the molecular mechanisms underlying microbial modulation of intestinal physiology, which might involve alterations in the intestinal physico-chemical environment, modifications in the gut microbiota, and/or direct interaction with mucosal epithelia and immune cells. Here we show by transcriptome analysis using DNA microarrays that the established probiotic bacterium, L. plantarum 299v, adapts its metabolic capacity in the human digestive tract for carbohydrate acquisition and expression of exo-polysaccharide and proteinaceous cell surface compounds. This report constitutes the first application of global gene expression profiling of a gut-adapted commensal microorganism in the human gut. Comparisons of the transcript profiles to those obtained for L. plantarum WCFS1 in germ-free mice revealed conserved L. plantarum responses indicative of a core transcriptome expressed in the mammalian gut and provide new molecular targets for determining microbial-host interactions affecting human health.
Project description:Numerous studies signify that diets rich in phytochemicals reduce the risk of inflammatory bowel diseases (IBDs). However, their effects are often not uniform among individuals, possibly due to inter-individual variation in gut microbiota. The host indigenous gut microbiota and their metabolites have emerged as factors that greatly influence the efficacy of dietary interventions. The biological activities, mechanisms of actions and the specific targets of several microbial metabolites are unknown. Urolithin A (UroA) is one such natural microbial metabolite, which showed (including our recent study) anti-carcinogenic, anti-oxidative and anti-inflammatory activities. The goal of the experiment to determine if Urolithin A blocks the genes induced by lipopolysaccharide (mimicking bacterial effects on colon) as well as determine effects of Urolithin A alone.
Project description:Coronary artery disease (CAD) is a widespread heart condition caused by atherosclerosis and influences millions of people worldwide. Early detection of CAD is challenging due to the lack of specific biomarkers. The gut microbiota and host-microbiota interactions have been well documented to affect human health. However, investigation that reveals the role of gut microbes in CAD is still limited. This study aims to uncover the synergistic effects of host genes and gut microbes associated with CAD through integrative genomic analyses.
Project description:Coronary artery disease (CAD) is a widespread heart condition caused by atherosclerosis and influences millions of people worldwide. Early detection of CAD is challenging due to the lack of specific biomarkers. The gut microbiota and host-microbiota interactions have been well documented to affect human health. However, investigation that reveals the role of gut microbes in CAD is still limited. This study aims to uncover the synergistic effects of host genes and gut microbes associated with CAD through integrative genomic analyses.
Project description:Lean nonalcoholic fatty liver disease (NAFLD) is increasingly recognized as a distinct clinical phenotype with limited evidence for effective non-pharmacological interventions and unclear mechanistic pathways. Aerobic exercise is recommended for NAFLD management, yet its effects and underlying gut microbiota–mediated mechanisms in lean NAFLD remain insufficiently characterized. This study is based on a randomized controlled trial (ClinicalTrials.gov identifier: NCT04882644) in which 100 adults with lean NAFLD were randomly assigned to a 3-month aerobic exercise intervention or usual care. 63 paired fecal samples were collected at baseline and after intervention. Gut microbiota profiles were generated using 16S rRNA gene sequencing. The dataset includes processed taxonomic abundance tables derived from fecal samples collected before and after the intervention. These data were used to characterize exercise-induced alterations in gut microbial diversity, composition, and functional potential, and to explore interindividual heterogeneity in microbiota responses to aerobic exercise in lean NAFLD. The microbiome data deposited in this series support integrative analyses with clinical phenotypes and circulating metabolomic profiles, aiming to elucidate gut microbiota–associated mechanisms underlying the metabolic benefits of aerobic exercise in lean NAFLD.
Project description:In recent years, the gut microbiota and derived metabolites have emerged as relevant players in modulating several brain functions, including energy balance control. This form of distant communication mirrors that of metabolic hormones (e.g., leptin, ghrelin), that convey information about the organism's energy status by exerting effects on diverse brain regions including the master homeostatic centre the hypothalamus. However, whether the hypothalamus is also able to influence gut microbiota composition remains enigmatic. Here, we present a proof-of-concept study designed to unravel this challenging question. To this aim, we employed chemogenetics (to selectively activate or inhibit the activity of hypothalamic POMC or AgRP neurons) or administered leptin or ghrelin centrally to mice. Subsequently, we conducted microbiota composition analysis throughout the gut using 16S rRNA gene sequencing. Our results showed that these brain interventions significantly changed the gut microbiota in an anatomical and short-term (2-4h) fashion. Transcriptomic analysis indicated that these changes were associated with the reconfiguration of neuronal and synaptic pathways in the duodenum concomitant with increased sympathetic tone. Interestingly, diet-induced obesity attenuated brain-mediated changes induced by leptin in gut microbiota communities and sympathetic activation. Our findings reveal a novel and unanticipated brain-to-gut axis that acutely attunes microbiota composition at fast timescales, with potential implications for meal-to-meal adjustments and systemic energy balance control.