Biology subjects

Yeliseyev, V.

Publications and source records attributed to Yeliseyev, V..

7 recordsLinked to original sources

bioRxiv2026

Blautia wexlerae Transforms Dietary Fatty Acids to Activate Enteroendocrine Signaling and Improve Metabolic Health in Mice and Humans

Metabolites produced by the gut microbiome influence host metabolic health, but how this occurs remains incompletely defined. Here, we report that a common human gut commensal, Blautia wexlerae, converts dietary fats into bioactive metabolites that induce gut hormone production to affect glucose metabolism and suppress appetite. We found that colonization with Blautia wexlerae correlated with healthier eating behaviors in humans. Blautia wexlerae encodes a unique acyl transferase and is capable of producing acyl amines from nutrient substrates. These Blautia acyl amines stimulated human enteroendocrine cells to secrete GLP-1 and other gut peptide hormones more potently than endogenously produced acyl amines. When fed to mice, acyl amines improved glycemic control and decreased appetite. In humans, higher stool levels of Blautia DNA encoding acyl amine synthesis genes correlated with leanness and decreased dietary fat intake. These results define a mechanism of action for how Blautia wexlerae affects host metabolic control.

microbiology↗

bioRxiv2025

Polyunsaturated fatty acids promote appetite via the microbiome-gut-brain axis

Appetite is regulated by nutrient-sensing systems that integrate long-term signals from energy stores and short-term cues from dietary intake, yet this regulation is increasingly disrupted by industrialized diets. Although the physiological effects of industrialized diets are well documented, the continued rise in metabolic and eating disorders underscores a critical gap in our understanding of how these diets shape neural regulation of eating behavior. Here, we tested how distinct properties of industrialized diets alter brain neurochemistry and change appetite. We probed the properties of an industrialized diet through contrasts targeting the overall diet pattern (Western vs. control), enriched macronutrients (fat vs. sugar), and isocaloric trade-offs of macronutrient variants (saturated fatty acids vs. polyunsaturated fatty acids [PUFA]). The most salient effects emerged from the finest-grained contrast: PUFA conditioning increased appetite through a mechanism involving elevated brain 5-hydroxyindoleacetic acid (5-HIAA), a primary serotonin catabolite associated with the gut microbiome. Fecal microbiota transplants into germ-free mice confirmed that the PUFA-conditioned gut microbiota carries an appetite-enhancing signature. Together, our findings delineate a diet-microbiome-gut-brain axis through which dietary components of industrialized diets can modulate appetite and contribute to altered eating behavior. Graphical abstract O_FIG O_LINKSMALLFIG WIDTH=200 HEIGHT=200 SRC="FIGDIR/small/667447v1_ufig1.gif" ALT="Figure 1"> View larger version (46K): org.highwire.dtl.DTLVardef@650141org.highwire.dtl.DTLVardef@1358b06org.highwire.dtl.DTLVardef@3a4c0corg.highwire.dtl.DTLVardef@156e685_HPS_FORMAT_FIGEXP M_FIG C_FIG One Sentence SummaryDietary polyunsaturated fatty acids enhance appetite via a gut microbiome-serotonergic pathway.

microbiology↗

bioRxiv2023

Beneficial metabolic effects of PAHSAs depend on the gut microbiota in diet-induced obese mice

Dietary lipids play an essential role in regulating the function of the gut microbiota and gastrointestinal tract, and these luminal interactions contribute to mediating host metabolism. PAHSAs are a class of lipids with anti-diabetic and anti-inflammatory properties, but whether the gut microbiota contributes to their beneficial effects on host metabolism is unknown. Here, we report that treating high fat diet (HFD)-fed germ-free mice with PAHSAs does not improve insulin sensitivity. However, transfer of feces from PAHSA-treated, but not Vehicle-treated, chow-fed mice increases insulin-sensitivity in HFD-fed germ free mice. Thus, the gut microbiota is necessary for and can transmit the insulin-sensitizing effects of PAHSAs in HFD-fed germ-free mice. Functional analyses of the cecal metagenome and lipidome of PAHSA-treated mice identified multiple lipid species that associate with the gut commensal Bacteroides thetaiotaomicron (Bt) and with insulin sensitivity resulting from PAHSA treatment. Bt supplementation in HFD-fed female mice prevented weight gain, reduced adiposity, improved glucose tolerance, fortified the colonic mucus barrier and reduced systemic inflammation versus chow-fed controls, effects that were not observed in HFD-fed male mice. Furthermore, ovariectomy partially reversed the beneficial Bt effects on host metabolism, indicating a role for sex hormones in mediating probiotic effects. Altogether, these studies highlight the fact that lipids can modulate the gut microbiota resulting in improvement in host metabolism and that PAHSA-induced changes in the microbiota result in at least some of their insulin-sensitizing effects in female mice.

physiology↗

bioRxiv2023

The TcdE holin drives toxin secretion and virulence in Clostridioides difficile.

Clostridioides difficile is the leading cause of healthcare associated infections. The Pathogenicity Locus (PaLoc) toxins TcdA and TcdB promote host disease. These toxins lack canonical N-terminal signal sequences for translocation across the bacterial membrane, suggesting alternate mechanisms of release, which have included targeted secretion and passive release from cell lysis. While the holin TcdE has been implicated in TcdA and TcdB release, its role in vivo remains unknown. Here, we show profound reductions in toxin secretion in tcdE mutants in the highly virulent strains UK1 (epidemic ribotype 027, Clade 3) and VPI10463 (ribotype 087, Clade 1). Notably, tcdE deletion in either strain rescued highly susceptible gnotobiotic mice from lethal infection by reducing acute extracellular toxin to undetectable levels, limiting mucosal damage, and enabling long-term survival, in spite of continued toxin gene expression in tcdE mutants. Our findings confirm TcdEs critical functions in vivo for toxin secretion and C. difficile virulence.

microbiology↗

bioRxiv2022

Clostridium scindens colonization of gnotobiotic mice promotes a chronic unresolving infection with Clostridioides difficile

The commensal Clostridium scindens has been regarded as a promising bacteriotherapeutic against Clostridioides difficile infection due to its ability to consume host factors that can promote C. difficile growth, and its production of the antimicrobial compound 1-acetyl-{beta}-carboline. We investigated C. scindens protective effects against C. difficile using defined colonization studies in gnotobiotic mice. Mice infected with C. difficile develop lethal infection within 48 hours. In contrast, 88% of mice pre-colonized with C. scindens survived acute infection with delayed C. difficile colonization, lower biomass, and toxin B levels at 24 hours after infection. However, two weeks post-challenge, surviving mice showed comparable levels of cecal C. difficile vegetative and spore biomass and toxin B, as seen during acute infection. After two weeks, co-colonized mice exhibited mucosal colonic hyperplasia with focal pseudomembranes, modeling a chronic and recurrent infection state. Our findings illustrate how the commensal microbiota can modulate host and pathogen interactions leading to chonic C. difficile carriage and infection.

microbiology↗

bioRxiv2021

Proanthocyanidin-enriched cranberry extract induces resilient bacterial community dynamics in a gnotobiotic mouse model

Cranberry consumption has numerous health benefits, with experimental reports showing its anti-inflammatory and anti-tumor properties. Importantly, microbiome research has demonstrated that the gastrointestinal bacterial community modulates host immunity, raising the question whether the cranberry-derived effect may be related to its ability to modulate the microbiome. Only a few studies have investigated the effect of cranberry products on the microbiome to date. Especially because cranberry is rich in dietary fibers, we do not know the extent of microbiome modulation that is caused solely by polyphenols, particularly proanthocyanidins (PACs). Since previous work has only focused on the long-term effects of cranberry extracts, in this study we investigated the effect of a water-soluble, polyphenol-rich cranberry juice extract (CJE) on the short-term dynamics of human-derived bacterial community in a gnotobiotic mouse model. CJE characterization revealed a high enrichment in PACs (57% PACs), the highest ever utilized in a microbiome study. In a 37-day experiment with a 10-day CJE intervention and 14-day recovery time, we profiled the microbiota via 16 rDNA sequencing and applied diverse time-series analytics methods to identify individual bacterial responses. We show that daily administration of CJE induces distinct dynamical patterns in bacterial abundances during and after treatment before recovering resiliently to pre-treatment levels. Specifically, we observed an increase of the immunomodulatory mucin degrading Akkermansia muciniphila after treatment, suggesting intestinal mucus accumulation due to CJE. Interestingly, this expansion coincided with an increase in the abundance of butyrate-producing Clostridia, a group of microbes known to promote numerous adaptive and innate anti-inflammatory phenotypes.

microbiology↗

bioRxiv2018

Bacteriophages dynamically modulate the gut microbiota and metabolome

The human gut microbiome is comprised of densely colonizing micro-organisms in dynamic interaction with each other and the host. While the bacterial component of the microbiome is under intense investigation, far less is known about how bacteriophages impact bacterial communities in the gut. We investigated the dynamic effects of phages on a model microbiome using gnotobiotic mice colonized by commensal bacteria that colonize the human infant gut, and found that phage predation not only directly impacts susceptible bacteria but also leads to cascading effects on other bacterial species via inter-bacterial interactions. Using metabolomic profiling, we also found that the shifts in the microbiome caused by phage predation have a direct consequence on the gut metabolome. Our work provides insight into the ecological importance of phages as modulators of bacterial colonization, and additionally suggests the potential impact of gut phages on the host with implications for the use of phages as therapeutic tools to rationally and precisely modulate the microbiome.

microbiology↗