Project description:Immune responses can significantly influence the gut microbiota by altering its structure and function, leading to rapid transcriptional and metabolic shifts in commensal microbes. However, the specific host mediators involved in this process and their effects on bacteria remain poorly elucidated. Here, using a flagellin injection model, we identified unsaturated long-chain fatty acids (uLCFAs) as broad modulators of bacterial gene expression released in the gut lumen during immune responses. In Blautia, a prominent commensal in humans and mice, uLCFAs triggered the expression of ohyA, encoding oleate hydratase, which produces non-toxic hydroxy-fatty acids with immunomodulatory properties. Remarkably, oral administration of uLCFAs to mice replicated many of the bacterial transcriptional changes induced by flagellin injection, revealing an intriguing parallel between immune responses and dietary habits. This molecular loop underscores the sophisticated interactions between host and microbiota, and sheds light on how immune responses affect gut commensal functions.
Project description:The human gut microbiota is crucial for degrading dietary fibres from the diet. However, some of these bacteria can also degrade host glycans, such as mucins, the main component of the protective gut mucus layer. Specific microbiota species and mucin degradation patterns are associated with inflammatory processes in the colon. Yet, it remains unclear how the utilization of mucin glycans affects the degradation of dietary fibres by the human microbiota. Here, we used three dietary fibres (apple pectin, β-glucan and xylan) to study in vitro the dynamics of colon mucin and dietary fibre degradation by the human faecal microbiota. The dietary fibres showed clearly distinguishing modulatory effects on faecal microbiota composition. The utilization of colon mucin in cultures led to alterations in microbiota composition and metabolites. Metaproteome analysis showed the central role of the Bacteroides in degradation of complex fibres while Akkermansia muciniphila was the main degrader of colonic mucin. This work demonstrates the intricacy of complex glycan metabolism by the gut microbiota and how the utilization of host glycans leads to alterations in the metabolism of dietary fibres. Metaproteomics analysis of this data reveals the functional activities of the bacteria in consortia, by this contributing to a better understanding of the complex metabolic pathways within the human microbiota that can be manipulated to maximise beneficial microbiota-host interactions.
Project description:Dietary lipids and gut microbiota may both influence adipose tissue physiology. By feeding conventional and germ-free mice high fat diets with different lipid compositon we aimed to investigate how dietary lipids and the gut microbiota interact to influence inflammation and metabolism in the liver
Project description:Chronic kidney disease (CKD) is a progressive condition characterized by renal fibrosis, with limited treatment options. Asiatic acid (AA), a triterpenoid derived from Centella asiatica, has shown renoprotective potential as a dietary supplement. This study integrated 16S rRNA sequencing, renal metabolomics, transcriptomics, and Metorigin analysis to investigate the renoprotective effects of AA in an adenine-induced CKD mouse model. AA significantly improved renal function, attenuated fibrosis, restored gut barrier integrity. Antibiotic depletion experiments demonstrated that an intact gut microbiota is required for the renoprotective effects of AA, supporting a functional link along the gut–kidney axis. AA modulated gut microbiota composition, notably enriching the beneficial genus Lachnospiraceae NK4A136 group. Multi-omics integration identified retinol metabolism as the key renal pathway rescued by AA, with metabolites including 9-cis-retinal and 4-hydroxyretinoic acid (4-OH-RA) showing strong negative correlations with renal injury markers.In vitro, 4-OH-RA suppressed fibrotic injury and oxidative stress in TGF-β1 stimulated tubular cells. These findings suggest that AA alleviates CKD in association with remodeling of the gut microbiota and reprogramming of renal retinol metabolism, highlighting its potential as a microbiota-targeting dietary supplement for renal protection., supporting its potential as a dietary supplement for countering renal fibrosis and supporting kidney health.
Project description:Dietary lipids and gut microbiota may both influence adipose tissue physiology. By feeding conventional and germ-free mice high fat diets with different lipid compositon we aimed to investigate how dietary lipids and the gut microbiota interact to influence inflammation and metabolism in epididymal adipiose tissue (EWAT)
Project description:Increasing the consumption of dietary fibre has been proposed to alleviate the progression of non-communicable diseases such as obesity, type 2 diabetes and cardiovascular disease, yet the effect of dietary fibre on host physiology remains unclear. In this study, we performed a multiple diet feeding study in C57BL/6J mice to compare high fat and high fat modified with dietary fibre diets on host physiology and gut homeostasis by combining proteomic, metagenomic, metabolomic and glycomic techniques with correlation network analysis. We observed significant changes in physiology, liver proteome, gut microbiota and SCFA production in response to high fat diet. Dietary fibre modification did not reverse these changes but was associated with specific changes in the gut microbiota, liver proteome, SCFA production and colonic mucin glycosylation. Furthermore, correlation network analysis identified gut bacterial-glycan associations.
Project description:Dietary lipids and gut microbiota may both influence adipose tissue physiology. By feeding conventional and germ-free mice high fat diets with different lipid compositon we aimed to investigate how dietary lipids and the gut microbiota interact to influence inflammation and metabolism in the liver Wild-type C57Bl/6 male mice 11 weeks of age were fed isocaloric diets (45% kcal fat) with either menhaden fish oil (Research Diets, D05122102) or lard (Research Diets, D10011202) for 11 weeks. Liver samples were harvested at the end of the experiment and analyzed by microarray.
Project description:Dietary lipids and gut microbiota may both influence adipose tissue physiology. By feeding conventional and germ-free mice high fat diets with different lipid compositon we aimed to investigate how dietary lipids and the gut microbiota interact to influence inflammation and metabolism in epididymal adipiose tissue (EWAT) Wild-type C57Bl/6 male mice 11 weeks of age were fed isocaloric diets (45% kcal fat) with either menhaden fish oil (Research Diets, D05122102) or lard (Research Diets, D10011202) for 11 weeks. Epididymal WAT samples were harvested at the end of the experiment and analyzed by microarray.
Project description:The human gut microbiota is crucial for degrading dietary fibres from the diet. However, some of these bacteria can also degrade host glycans, such as mucins, the main component of the protective gut mucus layer. Specific microbiota species and mucin degradation patterns are associated with inflammatory processes in the colon. Yet, it remains unclear how the utilization of mucin glycans affects the degradation of dietary fibres by the human microbiota. Here, we used three dietary fibres (apple pectin, β-glucan and xylan) to study in vitro the dynamics of colon mucin and dietary fibre degradation by the human faecal microbiota. The dietary fibres showed clearly distinguishing modulatory effects on faecal microbiota composition. The utilization of colon mucin in cultures led to alterations in microbiota composition and metabolites. Metaproteome analysis showed the central role of the Bacteroides in degradation of complex fibres while Akkermansia muciniphila was the main degrader of colonic mucin. This work demonstrates the intricacy of complex glycan metabolism by the gut microbiota and how the utilization of host glycans leads to alterations in the metabolism of dietary fibres. Metaproteomics analysis of this data reveals the functional activities of the bacteria in consortia, by this contributing to a better understanding of the complex metabolic pathways within the human microbiota that can be manipulated to maximise beneficial microbiota-host interactions. In this study two different mucin samples were used: commercial porcine gastric mucin and in house prepared porcine colonic mucin. This dataset analyses the proteome of: A) autoclaved porcine colonic mucin; B) not autoclaved porcine colonic mucin; C) porcine gastric mucin.
Project description:Analysis of breast cancer survivors' gut microbiota after lifestyle intervention, during the COVID-19 lockdown, by 16S sequencing of fecal samples.