Biology subjects

Allen-Vercoe, E.

Publications and source records attributed to Allen-Vercoe, E..

12 recordsLinked to original sources

bioRxiv2026

Comparisons among Yanomami populations reveal transitional gut microbiome configurations under urban influence

Urbanization influences gut microbiome composition and function, yet comparisons between contrasting lifestyles offer limited insight into which microbial features are most sensitive to increasing urbanization. We analyzed gut shotgun metagenomes from Yanomami participants, an Indigenous Amazonian people who maintain traditional livelihoods, across three geographically distinct populations with varying degrees of urban influence, as well as an urban Belgian cohort. Belgian and Yanomami microbiomes differed markedly in taxonomic composition and functional potential. The comparison between Bicho-Acu, the most urban-influenced Yanomami population, and Xamakorona, the least urban-exposed, revealed that although Bicho-Acu presented a broadly Yanomami-associated microbiome, it exhibited selected urban-associated features, including greater Bacteroides abundance and a higher relative abundance of genes involved in glycosaminoglycan degradation and secondary bile acid biosynthesis pathways. Furthermore, genus-level co-occurrence network connectivity showed an orderly shift across populations, declining progressively with increasing urban influence. Carbohydrate-active enzyme profiles further showed stronger non-starch-polysaccharide-associated signals in Belgium and resistant-starch-associated features in Xamakorona, suggesting distinct carbohydrate-processing strategies. Our findings support a model in which urbanization reshapes microbial composition, their ecological interactions, and metabolic capacity, with transitional configurations emerging through selective shifts across these dimensions.

microbiology↗

bioRxiv2026

Indigenous Yanomami gut microbiota protects against diet-induced metabolic dysfunction

Industrialization profoundly alters the human gut microbiota, reducing microbial diversity and eliminating taxa prevalent in non-industrialized populations. These microbiota alterations accompanying industrialization might contribute to the increasing prevalence of obesity and other chronic inflammatory diseases, yet direct experimental evidence remains lacking. We compared the gut microbiota of Indigenous Brazilian Yanomami and urban Belgian donors and transplanted these into germ-free (GF) mice subjected to high-fat diet (HFD). The Yanomami microbiota exhibited greater richness and distinct composition enriched for VANISH (Volatile and/or Associated Negatively with Industrialized Societies of Humans) taxa. Transplantation of Yanomami microbiota significantly attenuated HFD-induced metabolic dysfunction, reducing weight gain, diabetes incidence, and promoting adipose and hepatic Th2 immunity. Yanomami-derived microbial communities displayed enhanced ecological stability and enrichment for short-chain fatty acid-associated taxa and metabolic functions post-HFD. Our findings demonstrate that the microbiota from low-urbanization populations confer protection against diet-induced metabolic disease, highlighting ecological resilience and specific microbial functions as potential targets for microbiota-inspired therapeutics.

microbiology↗

bioRxiv2026

Diet-derived Microbial Metabolites Modulate Stress-Responsive Gene Expression in Germ-free Zebrafish

The gut microbiome plays a pivotal role in overall host health, yet the extent at which diet-derived microbial metabolites affect neurodevelopment and inflammation remains unclear. Here, we employed the robogut bioreactor system seeded with fecal samples from two healthy pediatric donors to generate microbial communities exposed to four different diets: low fiber Western (LFW), high fiber Western (HFW), Mediterranean (MED), and Yanomami (YAN), as well as three fiber supplements: fruit and vegetable fiber (FVF), cereal fiber (CRF), and resistant starch fiber (RSF). Metabolites produced by these microbial communities were isolated and applied to germ-free zebrafish (Danio rerio) embryos to assess their effects on neurodevelopment and inflammatory gene expression under basal and stress-induced conditions. Despite minimal changes in microbial composition across diets and fiber sources, significant differences in short-chain fatty acid concentrations were observed. Metabolite treatments had limited effects on the expression of neural and inflammatory genes under basal conditions. Under stress conditions, metabolites from any diet mitigated stress-induced bdnf expression, suggesting a possible modulatory role of microbial metabolites on stress responses. Overall, these findings highlight the resilience of microbial communities to dietary changes and underscore the importance of microbial metabolite output and its donor-specific nature in influencing host neurodevelopment and immune responses.

developmental biology↗

bioRxiv2025

Enterocloster citroniae and related gut microbiome species modulate Vibrio cholerae biofilm formation through the production of bioactive small molecules

Cholera is a diarrheal disease that affects millions of people globally. Although the causative agent, Vibrio cholerae, has been extensively studied in isolation, investigation of its interactions with the gut microbiota started relatively recently. We and others previously showed that microbiota-derived metabolites significantly influence V. cholerae behavior. By investigating how an organic extract of human feces affects V. cholerae gene expression, we showed that gut metabolites strongly suppress swimming motility, a trait important for host colonization. Interestingly, extracts of pure cultures of a gut commensal, Enterocloster citroniae, recapitulated this inhibition. Here, we present a comprehensive examination of the effect of small molecules produced by E. citroniae and related species on V. cholerae behavior. We show that E. citroniae small molecules inhibit motility by various V. cholerae strains, and that several phylogenetically related species produce this activity, although the magnitude of the effect varies between strains. Using biofilm formation assays in static and flow conditions, we show that V. cholerae strongly induces biofilm formation in response to E. citroniae metabolites. Transcriptome and reporter analyses showed that several genes involved in synthesis of an extracellular polysaccharide are induced by E. citroniae metabolites. Lastly, we show that V. cholerae interactions with host cells are also modulated by this commensal. These findings advance our understanding of microbiome-pathogen interactions and how commensal bacteria influence V. cholerae virulence through the production of small molecules. In the future, this knowledge may be used to design novel microbiome-based therapeutic approaches to combat cholera and other infections. ImportanceThe human gut is home to a dense and rich community of microbes termed microbiota. This community has critical functions for host health, including protection against enteric pathogens. Despite this important role, we have only recently scratched the surface of the interactions that occur between members of the microbiota and pathogenic invaders. Cholerae is a disease that still causes significant morbidity and mortality worldwide. Studying how the causative agent, Vibrio cholerae, interacts with the microbiota will have implications not only for our understanding of this important microbial community, but may also lead to the development of new therapeutic strategies against cholera and potentially other infectious diseases.

microbiology↗

bioRxiv2025

Assessment of ecological fidelity of human microbiome-associated mice in observational studies and an interventional trial

Composition and function of the gut microbiome is associated with diverse health conditions and treatment responses. Human microbiota-associated (HMA) mouse models are used to establish causal links for these associations but have important limitations. We assessed the fidelity of HMA mouse models to recapitulate ecological responses to a microbial consortium using stools collected from a human clinical trial. HMA mice were generated using different routes of consortium exposure and their ecological features were compared to human donors by metagenomic sequencing. HMA mice were more similar in gut composition to other mice than their respective human donors, with taxa including Akkermansia muciniphila and Bacteroides species enriched in mouse recipients. A limited repertoire of microbes was able to engraft into HMA mice regardless of route of consortium exposure. In publicly available HMA mouse datasets from four distinct health conditions, we confirmed our observation that a taxonomically restricted set of microbes reproducibly engrafts in HMA mice and observed that stool microbiome composition of HMA mice were more like other mice than their human donor. Our data suggest that HMA mice are limited models to assess the ecological impact of microbial consortia, with ecological effects in HMA mice being more strongly associated with host species than donor stool ecology or ecological responses to treatment in humans. Comparisons to published studies suggest this may be due to comparatively large host-species effects that overwhelm ecological effects of treatment in humans that HMA models aim to recapitulate. ImportanceHuman microbiota-associated (HMA) mice are models that better represent human gut ecology compared to conventional laboratory mice and are commonly used to test the effect of the gut microbiome on disease or treatment response. We evaluated the fidelity of using HMA mice as avatars of ecological response to a human microbial consortium, MET4. Our results show that HMA mice in our cohort and across other published studies are more similar to each other than the human donors or inoculum they are derived from and harbour a taxonomically restricted gut microbiome. These findings highlight the limitations of HMA mice in evaluating the ecological effects of complex human microbiome-targeting interventions, such as microbial consortia.

microbiology↗

bioRxiv2022

Alterations in intestinal Proteobacteria and antimicrobial resistance gene burden in individuals administered microbial ecosystem therapeutic (MET-2) for recurrent Clostridioides difficile infection

Intestinal colonisation with pathogens and antimicrobial resistant organisms (AROs) is associated with increased risk of infection. Fecal microbiota transplant (FMT) has successfully been used to cure recurrent Clostridioides difficile infection (rCDI) and to decolonise intestinal AROs. However, FMT has significant practical barriers to implementation. A microbial consortium, microbial ecosystem therapeutic (MET)-2, is an alternative to FMT for the treatment of rCDI. It is unknown whether MET-2 is associated with decreases in pathogens and antimicrobial resistance genes (ARGs). We conducted a post-hoc metagenomic analysis of stool collected from two interventional studies of MET-2 (published) and FMT (unpublished) for rCDI treatment to understand if MET-2 had similar effects to FMT for decreasing pathogens and ARGs as well as increasing anaerobes. Patients were included in the current study if baseline stool had Proteobacteria relative abundance [≥]10% by metagenomic sequencing. We assessed pre- and post-treatment Proteobacteria, obligate anaerobe and butyrate-producer relative abundances and total ARGs. MET-2 and FMT were associated with decreases in Proteobacteria relative abundance as well as increases in obligate anaerobe and butyrate-producer relative abundances. The microbiota response remained stable over 4 or 6 months for MET-2 and FMT, respectively. MET-2, but not FMT, was associated with a decrease in the total number of ARGs. MET-2 is a potential therapeutic strategy for ARO/ARG decolonisation and anaerobe repletion.

microbiology↗

bioRxiv2022

Bacterial lipopolysaccharide modulates immune response in the colorectal tumor microenvironment

Immune responses can have opposing effects in colorectal cancer (CRC), the balance of which may determine whether a cancer regresses, progresses, or potentially metastasizes. These effects are evident in CRC consensus molecular subtypes (CMS) where both CMS1 and CMS4 contain immune infiltrates yet have opposing prognoses. The microbiome has previously been associated with CRC and immune response in CRC but has largely been ignored in the CRC subtype discussion. Using CMS subtyping, we aimed to determine the contributions of the microbiome to the pleiotropic effects evident in immune-infiltrated subtypes. We integrated host gene-expression and meta-transcriptomic data to determine the link between immune characteristics and microbiome contributions in these subtypes and identified lipopolysaccharide (LPS) binding as a potential functional mechanism. We identified candidate bacteria with LPS properties that could affect immune response, focusing on Fusobacterium periodonticum and Bacteroides fragilis in CMS1, and Porphyromonas asaccharolytica in CMS4. Treatment of peripheral blood mononuclear cells (PBMCs) with LPS isolated from these bacteria showed that F. periodonticum stimulates cytokine production in PBMCs while both B. fragilis and P. asaccharolytica had an inhibitory effect. Furthermore, LPS from the latter two species can inhibit the immunogenic properties of F. periodonticum LPS when co-incubated with PBMCs. We propose that different microbes in the CRC tumor microenvironment can alter the local immune activity, with important implications for prognosis and treatment response.

cancer biology↗

bioRxiv2021

Modulation of the host cell transcriptome and epigenome by Fusobacterium nucleatum

Fusobacterium nucleatum (Fn) is a ubiquitous opportunistic pathogen with an emerging role as an oncomicrobe in colorectal and other cancer types. Fn can adhere to and invade host cells in a manner that varies across Fn strains and host cell phenotypes. Here we performed pairwise co-cultures between three Fn strains and two immortalized primary host cell types (colonic epithelial cells and vascular endothelial cells) followed by RNA-seq and ChIP-seq to investigate transcriptional and epigenetic host cell responses. We observed that Fn-induced host cell transcriptional modulation involves strong upregulation of genes related to immune migration and inflammatory processes, such as TNF, CXCL8, CXCL1, and CCL20. Further, we identified genes strongly upregulated specifically in conditions of host cell invasion, including overexpression of both EFNA1 and LIF, two genes commonly upregulated in colorectal cancer and associated with poor patient outcomes, and PTGS2 (COX2), a gene associated with the protective effect of aspirin in the colorectal cancer setting. Interestingly, we also observed downregulation of numerous histone modification genes upon Fn exposure. To further explore this relationship, we used the ChIP-seq data to annotate chromatin states genome-wide. We found significant chromatin remodeling following Fn exposure in conditions of host cell invasion, with substantial increases in the frequency of states corresponding to active enhancers as well as low signal or quiescent states. Thus, our results highlight increased inflammation and chemokine gene expression as conserved host cell responses to Fn exposure, and extensive host cell epigenomic changes associated with Fn host cell invasion. These results extend our understanding of Fn as an emerging pathogen and highlight the importance of considering strain heterogeneity and host cell phenotypic variation when exploring pathogenic mechanisms of Fn.

genomics↗

bioRxiv2020

Invasion by Fusobacterium nucleatum Causes Upregulation of dll4 and klf4 Expression in Caco-2 Cells

Fusobacterium nucleatum is an emerging microbe of importance in the pathogenesis of colorectal cancer. Strains of this enigmatic bacterial species vary in their capacity to invade human epithelial cells, a virulence determinant which has important implications in disease. Here, we infected human colorectal epithelial (Caco-2) cells in vitro with a known, highly invasive strain of F. nucleatum isolated from a Crohns Disease patient, as well as a further invasive isolate of F. nucleatum derived from a colorectal cancer tumour. We used transcriptional profiling to determine the human genes upregulated during the invasion process compared to exposure to a non-invasive E.coli control strain. Infection with F. nucleatum strains resulted in the upregulation of several host genes, including two associated with tumorigenesis: dll4 and klf4.

cancer biology↗

bioRxiv2018

Drivers of human gut microbial community assembly: Coadaptation, determinism and stochasticity

Microbial community assembly is a complex process shaped by multiple factors, including habitat filtering, species assortment and stochasticity. Understanding the relative importance of these drivers would enable scientists to design strategies initiating a desired reassembly for e.g., remediating low diversity ecosystems. Here, we aimed to examine if a human fecal-derived defined microbial community cultured in bioreactors assembled deterministically or stochastically, by completing replicate experiments under two growth medium conditions characteristic of either high fiber or high protein diets. Then, we recreated this defined microbial community by matching different strains of the same species sourced from distinct human donors, in order to elucidate whether coadaptation of strains within a host influenced community dynamics. Each defined microbial ecosystem was evaluated for composition using marker gene sequencing, and for behaviour using 1H-NMR based metabonomics. We found that stochasticity had the largest influence on the species structure when substrate concentrations varied, whereas habitat filtering greatly impacted the metabonomic output. Evidence of coadaptation was elucidated from comparisons of the two communities; we found that the artificial community tended to exclude saccharolytic Firmicutes species and was enriched for metabolic intermediates, such as Stickland fermentation products, suggesting overall that polysaccharide utilization by Firmicutes is dependent on cooperation.

microbiology↗

bioRxiv2018

Illuminating the microbiome’s dark matter: a functional genomic toolkit for the study of human gut Actinobacteria

Despite the remarkable evolutionary and metabolic diversity found within the human microbiome, the vast majority of mechanistic studies focus on two phyla: the Bacteroidetes and the Proteobacteria. Generalizable tools for studying the other phyla are urgently needed in order to transition microbiome research from a descriptive to a mechanistic discipline. Here, we focus on the Coriobacteriia class within the Actinobacteria phylum, detected in the distal gut of 90% of adult individuals around the world, which have been associated with both chronic and infectious disease, and play a key role in the metabolism of pharmaceutical, dietary, and endogenous compounds. We established, sequenced, and annotated a strain collection spanning 14 genera, 8 decades, and 3 continents, with a focus on Eggerthella lenta. Genome-wide alignments revealed inconsistencies in the taxonomy of the Coriobacteriia for which amendments have been proposed. Re-sequencing of the E. lenta type strain from multiple culture collections and our laboratory stock allowed us to identify errors in the finished genome and to identify point mutations associated with antibiotic resistance. Analysis of 24 E. lenta genomes revealed an \"open\" pan-genome suggesting we still have not fully sampled the genetic and metabolic diversity within this bacterial species. Consistent with the requirement for arginine during in vitro growth, the core E. lenta genome included the arginine dihydrolase pathway. Surprisingly, glycolysis and the citric acid cycle was also conserved in E. lenta despite the lack of evidence for carbohydrate utilization. We identified a species-specific marker gene and validated a multiplexed quantitative PCR assay for simultaneous detection of E. lenta and specific genes of interest from stool samples. Finally, we demonstrated the utility of comparative genomics for linking variable genes to strain-specific phenotypes, including antibiotic resistance and drug metabolism. To facilitate the continued functional genomic analysis of the Coriobacteriia, we have deposited the full collection of strains in DSMZ and have written a general software tool (ElenMatchR) that can be readily applied to novel phenotypic traits of interest. Together, these tools provide a first step towards a molecular understanding of the many neglected but clinically-relevant members of the human gut microbiome.

microbiology↗

bioRxiv2017

FplA From Fusobacterium nucleatum Is A Type Vd Autotransporter Phospholipase With A Proposed Role In Altered Host Signaling And Evasion Of Autophagy

Fusobacterium nucleatum is a pathogenic oral bacterium that is linked to multiple human infections and colorectal cancer. While most Gram-negative pathogens utilize secretion systems for cellular invasion and infection, F. nucleatum lacks Type I, II, III, IV, and VI secretion. By contrast, F. nucleatum strains are enriched in Type V secreted autotransporters, which are Gram-negative bacterial virulence factors critical for binding and entry into host cells. Here we present the first biochemical characterization of a F. nucleatum Type Vd phospholipase class A1 autotransporter (strain ATCC 25586, gene FN1704) that we hereby rename Fusobacterium phospholipase autotransporter (FplA). FplA is expressed as a full-length 85 kDa outer membrane embedded protein, or as a truncated phospholipase domain that remains associated with the outer membrane. Using multiple FplA constructs we characterized lipid substrate specificity, potent inhibitors, and chemical probes to detect and track this enzyme family. While the role of FplA is undetermined in F. nucleatum virulence, homologous phospholipases from intracellular pathogens are critical for vacuole escape, altered host signaling, and intracellular survival. We hypothesize that upon intracellular invasion of the host, FplA could play a role in phagosomal escape, subversion of autophagy, or eicosanoid-mediated inflammatory signaling, as we show that FplA binds with high affinity to host phosphoinositide signaling lipids critical to these processes. Our identification of substrates, inhibitors, and chemical probes for FplA, in combination with an fplA gene deletion strain, encompass a powerful set of tools for the future analysis of FplA in vivo. In addition, these studies will guide the biochemical characterization of additional Type Vd autotransporter phospholipases.\n\nIMPORTANCEF. nucleatum is an emerging pathogen that is linked to the pathogenesis of colorectal cancer, yet there is a critical knowledge gap in the mechanisms used by this bacterium to elicit changes in the host for intracellular entry and survival. As phospholipases are critical virulence factors for intracellular bacteria to initiate vacuole lysis, cell-to-cell spread, and evasion of autophagy, we set out to characterize a unique Type Vd secreted phospholipase A1 enzyme from F. nucleatum. Our results show a potential role for modulating host signaling pathways through cleavage of phosphoinositide dependent signaling lipids. These studies open the door for further characterization of this unique enzyme family in bacterial virulence, host-pathogen interactions, and for F. nucleatum, in colorectal carcinogenesis.

microbiology↗