Gut microbes modulate the effects of the flavonoid quercetin on atherosclerosis
NPJ Biofilms Microbiomes. 2025 Jan 10;11(1):12. doi: 10.1038/s41522-024-00626-1.
The gut bacterial metabolism of dietary flavonoids produces a variety of phenolic acids, whose contributions to health remain poorly understood. Using gnotobiotic models and metabolomics approaches, we found that gut microbes influences the effects of quercetin on atherosclerosis, potentially mediated by bacterial metabolites derived from the flavonoid.
Gut bacterial metabolism contributes to host global purine homeostasis
Cell Host Microbe. 2023 Jun 14;31(6):1038-1053.e10. doi: 10.1016/j.chom.2023.05.011.
In the paper, we identified gut bacterial taxa spanning multiple phyla, including Bacillota, Fusobacteriota, and Pseudomonadota, that use multiple purines, including uric acid (UA) as carbon and energy sources anaerobically. We found a gene cluster that encodes key steps of anaerobic purine degradation and that is widely distributed among gut-dwelling bacteria. Furthermore, we showed that colonization of gnotobiotic mice with purine-degrading bacteria modulates levels of UA and other purines in the gut and systemically. Thus, gut microbes are important drivers of host global purine homeostasis and serum UA levels, and gut bacterial catabolism of purines may represent a mechanism by which gut bacteria influence health.
Dissecting the impact of dietary fiber type on atherosclerosis in mice colonized with different gut microbial communities
NPJ Biofilms Microbiomes. 2023 Jun 3;9(1):31. doi: 10.1038/s41522-023-00402-7.
Dietary fiber consumption has been linked with improved cardiometabolic health, however, human studies have reported large interindividual variations in the observed benefits. Using germ-free mice with fecal samples from three human donors and diets supplemented with either a mix of 5 fermentable fibers (FF) or non-fermentable cellulose control diet, we found that atheroprotection in response to FF is not universal and is influenced by the gut microbiome.
Genetic mapping of microbial and host traits reveals production of immunomodulatory lipids by Akkermansia muciniphila in the murine gut
Nat Microbiol. 2023 May; 8(3):424-440. doi: 10.1038/s41564-023-01326-w.
The molecular bases of how host genetic variation impacts the gut microbiome remain largely unknown. Here we used a genetically diverse mouse population and applied systems genetics strategies to identify interactions between host and microbe phenotypes including microbial functions, using faecal metagenomics, small intestinal transcripts and caecal lipids that influence microbe-host dynamics. We found overlapping QTL for the abundance of Akkermansia muciniphila and caecal levels of ornithine lipids. Follow-up in vitro and in vivo studies revealed that A. muciniphila is a major source of these lipids in the gut, provided evidence that ornithine lipids have immunomodulatory effects. Collectively, these results suggest that ornithine lipids are potentially important for A. muciniphila-host interactions and support the role of host genetics as a determinant of responses to gut microbes.
The human gut microbiota contributes to type-2 diabetes non-resolution 5-years after Roux-en-Y gastric bypass
Gut Microbes. 2022 Jan-Dec;14(1):2050635. doi: 10.1080/19490976.2022.2050635.
Roux-en-Y gastric bypass (RYGB) effectively induces weight loss and improves type-2 diabetes (T2D), but outcomes vary. Given its impact on gut microbiota (GM), we investigated its role in metabolic benefits. In a 5-year study of 100 patients with baseline T2D, hierarchical clustering identified two groups: Severe and Mild T2D cases. Nanopore sequencing revealed that unresolved severe T2D was linked to an enrichment of Bacteroidia, including Phocaeicola dorei, Bacteroides fragilis, and Bacteroides caecimuris. This enrichment was absent in patients with better metabolic outcomes. A separate cohort showed that Bacteroidia overrepresentation was already present preoperatively in severe T2D cases. To explore causality, fecal transplants from 13 patients into mice demonstrated that Severe-donor GM impaired glucose tolerance and insulin sensitivity, independent of body weight. GM sequencing confirmed bacterial feature transfer linked to metabolic dysfunction. These findings highlight the GM’s role in long-term glucose metabolism after RYGB.
The emerging role of gut microbial metabolism on cardiovascular disease
Curr Opin Microbiol. 2019 Aug:50:64-70. doi: 10.1016/j.nib.2019.09.007.
The purpose of this review is to discuss recent progress in our understanding of how gut microbial metabolism of food influences the development of CVD and to outline experimental approaches that can be useful for addressing crucial knowledge gaps in the field.
Interactions between Roseburia intestinalis and diet modulate atherogenesis in a murine model
Nat Microbiol. 2018 Dec;3(12):1461-1471. doi: 10.1038/s41564-018-0272-x.
Humans with metabolic and inflammatory diseases frequently harbour lower levels of butyrate-producing bacteria in their gut. However, it is not known whether variation in the levels of these organisms is causally linked with disease development and whether diet modifies the impact of these bacteria on health. Here we use germ-free apolipoprotein E-deficient mice colonized with synthetic microbial communities that differ in their capacity to generate butyrate to demonstrate that Roseburia intestinalis interacts with dietary plant polysaccharides to: impact gene expression in the intestine, directing metabolism away from glycolysis and toward fatty acid utilization; lower systemic inflammation; and ameliorate atherosclerosis. Our results illustrate how modifiable diet-by-microbiota interactions impact cardiovascular disease, and suggest that interventions aimed at increasing the representation of butyrate-producing bacteria may provide protection against atherosclerosis.
Fecal Aliquot Straw Technique (FAST) allows for easy and reproducible subsampling: assessing interpersonal variation in TMAO accumulation
Microbiome. 2018 May 18;6(1):91. doi: 10.1186/s40168-018-0458-8.
The Fecal Aliquot Straw Technique (FAST) is a convenient and reproducible method for fecal sample storage and subsampling, preserving viable microbes for microbiome studies. Using a straw, samples can be collected from freshly voided or refrigerated (4°C) feces without freezing. 16S rRNA sequencing confirmed high reproducibility, with minimal taxonomic variation between aliquots. Transplantation into germ-free mice retained ~80% of the donor’s microbiota, with notable interpersonal variation in choline metabolism. FAST enables repeated subsampling without thawing, requiring minimal resources, making it ideal for both laboratory and field research.
Metabolic, Epigenetic, and Transgenerational Effects of Gut Bacterial Choline Consumption
Cell Host Microbe. 2017 Sep 13;22(3):279-290.e7. doi: 10.1016/j.chom.2017.07.021.
Choline is an essential nutrient and methyl donor required for epigenetic regulation. Here, we assessed the impact of gut microbial choline metabolism on bacterial fitness and host biology by engineering a microbial community that lacks a single choline-utilizing enzyme. Our results indicate that choline-utilizing bacteria compete with the host for this nutrient, significantly impacting plasma and hepatic levels of methyl-donor metabolites and recapitulating biochemical signatures of choline deficiency. Mice harboring high levels of choline-consuming bacteria showed increased susceptibility to metabolic disease in the context of a high-fat diet. Furthermore, bacterially induced reduction of methyl-donor availability influenced global DNA methylation patterns in both adult mice and their offspring and engendered behavioral alterations. Our results reveal an underappreciated effect of bacterial choline metabolism on host metabolism, epigenetics, and behavior. This work suggests that interpersonal differences in microbial metabolism should be considered when determining optimal nutrient intake requirements.
Commensal bacteria at the crossroad between cholesterol homeostasis and chronic inflammation in atherosclerosis
J Lipid Res. 2017 Mar;58(3):519-528. doi: 10.1194/jlr.M072165.
The gut microbiota were shown to play critical roles in the development of atherosclerosis, but the detailed mechanism is limited. The purpose of this study is to clarify the influence of gut microbiota on atherogenesis via lipid metabolism and systemic inflammation. Germ-free or conventionally raised (Conv) ApoE-deficient (ApoE-/-) mice were fed chow diet and euthanized at 20 weeks of age. We found that the lack of gut microbiota in ApoE-/- mice caused a significant increase in the plasma and hepatic cholesterol levels compared with Conv ApoE-/- mice. The absence of gut microbiota changed the bile acid composition in the ileum, which was associated with activation of the enterohepatic fibroblast growth factor 15, fibroblast growth factor receptor 4 axis, and reduction of cholesterol 7α-hydroxylase and hepatic bile acid synthesis, resulting in the accumulation of liver cholesterol content. However, we found that the lack of microbiota caused a significant reduction in atherosclerotic lesion formation compared with Conv ApoE-/- mice, which might be associated with the attenuation of lipopolysaccharide-mediated inflammatory responses. Our findings indicated that the gut microbiota affected both hypercholesterolemia and atherogenesis in mice.
