ABSTRACT: Metagenome assembly of PRJEB64861 data set (Impact of dietary interventions on pre-diabetic oral and gut microbiome, metabolites and cytokines)
Project description:Insufficient dietary fiber intake is strongly associated with gut microbiome dysfunction and an increased risk of noncommunicable diseases. Synergistic synbiotics, which pair defined microbial strains with their preferred carbohydrate substrates, offer a promising strategy to restore these functions. However, the rational design of such interventions remains challenging by insufficient understanding of microbial fiber-degrading capacities and the host-relevant bioactivities of fermentation-derived metabolites. Here, we identify human colonic commensal Bacteroides intestinalis (B. intestinalis) as a key microbial mediator of dietary fiber-driven metabolic, immune, and neuronal benefits. We demonstrate that the synergistic interaction between B. intestinalis and its preferred substrate, insoluble wheat arabinoxylan abundant in dietary fiber, enhances the production of anti-inflammatory, antioxidant, and anti-diabetic phenolic compounds and bile acid species. These metabolic effects are accompanied by coordinated transcriptional remodeling in the colon and spleen that improve circadian rhythm regulation, lipid metabolism, and immune defense. Importantly, these beneficial effects are preserved in conventionally raised mice with established high fat diet-induced obesity, where BI and inWAX improves glucose tolerance along with an increased production of neuroactive compounds. Our findings uncover a mechanistic framework linking B. intestinalis-mediated fiber fermentation to gut–liver–brain crosstalk and establish a rational foundation for precision synbiotic design.
Project description:Opioid Use Disorder (OUD) is a neuropsychiatric condition associated with tremendous medical and social consequences. Despite this burden, current pharmacotherapies for OUD are ineffective or intolerable for many patients. As such, interventions aimed at promoting overall health and resilience against OUD are of immense clinical and societal interest. Recently, treatment with a Bioactive Dietary Polyphenol Preparation (BDPP) was shown to promote behavioral resilience and adaptive neuroplasticity in multiple models of neuropsychiatric disease. Here, we assessed effects of BDPP treatment on behavioral and molecular responses to repeated morphine treatment. We find that BDPP pre-treatment alters responses across the dose range for both locomotor sensitization and conditioned place preference. Most notably, polyphenol treatment consistently reduced formation of preference at low dose (5mg/kg) morphine but enhanced it at high dose (15mg/kg). In parallel, we performed transcriptomic profiling of the nucleus accumbens, which again showed a dose x polyphenol interaction. At high dose morphine, BDPP pre-treatment potentiated gene expression changes induced by morphine particularly for genes related to synaptic function. We also profiled microbiome composition and function, as polyphenols are metabolized by the microbiome and can act as prebiotics. The profile revealed polyphenol treatment markedly altered microbiome composition and function, particularly in the low dose morphine group. Finally, we investigated involvement of the SIRT1 histone deacetylase, and the role of specific polyphenol metabolites in these behavioral phenotypes. Taken together, these results demonstrate that polyphenols have robust dose-dependent effects on behavioral and physiological responses to morphine and lay the foundation for future translational work.
Project description:HuMiChip was used to analyze human oral and gut microbiomes, showing significantly different functional gene profiles between oral and gut microbiome. The results were used to demonstarte the usefulness of applying HuMiChip to human microbiome studies.
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:The gut microbiome plays a crucial role in modulating human immunity. Previously, we found that antibiotic-induced microbiome perturbation affected influenza vaccine responses depending on pre-existing immunity levels. However, its impact on primary responses remains unclear. Here, we employed a systems biology approach to analyze the impact of antibiotic administration on primary and secondary immune responses to the rabies vaccine in humans. Antibiotic administration disrupted the microbiome, reducing gut bacterial load and causing long-lasting reduction in commensal diversity. This alteration was associated with reduced rabies-specific humoral responses. Multi-omics profiling revealed that antibiotic administration induced: 1) an enhanced pro-inflammatory signature early after vaccination, 2) a shift in the balance of vaccine-specific T-helper 1(Th1) to T-follicular-helper response towards Th1 phenotype, 3) profound alterations in metabolites, particularly in secondary bile acids in blood. By integrating multi-omics datasets, we generated a multi-scale, multi-response network that revealed key regulatory nodes including the microbiota, secondary bile acids, and humoral immunity to vaccination.
Project description:Polyphenols are promising therapeutics for Crohn’s disease (CD), yet their bioavailability is largely dependent on the gut microbiome. The bioactive metabolites, metabolic pathways, and anti-inflammatory mechanisms underlying their effects remain poorly defined. Through integrated multi-omics and dietary analysis, we identified hippuric acid as a reduced metabolite in CD patients and a biomarker of polyphenol–microbiome interactions. We further demonstrate that hydrocinnamic acid, derived from microbiome metabolism of dietary trans-cinnamic acid and subsequently converted to hippuric acid by the host, ameliorates colitis in mice via the PPAR-γ pathway. Notably, we identified Bifidobacterium breve Bbr60 and Escherichia coli FAH as novel hydrocinnamic acid producers, complementing the established pathway in Clostridium sporogenes and suggesting additional microbial contributors. Collectively, our findings establish hydrocinnamic acid as a diet-dependent, colon-produced, mild PPAR-γ agonist with the potential to minimize adverse effects associated with traditional PPAR-γ agonists. This work establishes a foundation for developing microbiota-targeted, polyphenol-based therapeutic strategies for CD patients.
Project description:Dietary glucosylceramide (GC) improves skin barrier function. To elucidate the molecular mechanisms involved, we used a microarray system to analyze mRNA expression in SDS-treated dorsal skin of hairless mouse. Transepidermal water loss of mouse skin was increased by SDS treatment and the increase was significantly reduced by prior oral administration of glucosylceramides. Microarray-evaluated mRNA expression ratios showed statistically significant increase of expression of genes related to cornified envelope and tight junction formation versus all genes in glucosylceramide-fed/SDS-treated mouse skin. We then examined the contribution of glucosylceramide metabolites to tight junction formation of cultured keratinocytes. SDS treatment of cultured keratinocytes significantly decreased the transepidermal electrical resistance, and the decrease was significantly ameliorated in the presence of sphingosine or phytosphingosine, the major metabolites of glucosylceramide. These results suggest that oral administration of glucosylceramide improves skin barrier function by upregulating genes associated with both cornified envelope and tight junction formation. Two-condition experiment, effect of oral intake of GC on mice skin before SDS treatment (0d), and after SDS treatment(2d), Biological replicates: 3 replicates for 0d, 4 replicates for 2d.