bioRxiv Science⌕ Search

bioRxiv · 10.1101/2025.03.21.641387

Profound taxonomic and functional gut microbiota alterations associated with trichuriasis: cross-country and country-specific patterns

Abstract

BackgroundThe human gastrointestinal microbiota plays a crucial role in immune modulation, metabolism, and pathogen resistance. Soil-transmitted helminth (STH) infections, including Trichuris trichiura (whipworm), significantly alter gut microbial composition, yet the extent and functional consequences of these changes remain underexplored across different geographical regions. This study investigates the taxonomic and functional impacts of T. trichiura on gut microbiota in three endemic regions - Cote dIvoire, Laos, and Tanzania - using a unified high-resolution metagenomic sequencing approach. ResultsThis study reveals extensive gut microbiota disruptions linked to T. trichiura infection, with both regional and cross-country patterns. A core signature found across all study sites includes depletion of Faecalibacterium prausnitzii and Eubacterium rectale (Short-chain fatty acids (SCFA) producers) and enrichment of mucin-degrading bacteria (Ruminococcus, Bacteroides), alongside increased host-derived carbohydrate metabolism. Infection destabilized microbial networks, characterized by reduced connectivity and clustering, with opportunistic taxa such as Segatella copri emerging as network hubs across regions, indicating a shared ecological response. Both taxonomic and functional disruptions exhibited a combination of conserved and region-specific patterns; for example, whereas certain taxa, such as Prevotella and Streptococcus, showed notable geographic variability, specific functional changes, such as SCFA depletion and mucin degradation, were consistently observed across sites. These conserved functional changes suggest that T. trichiura imposes similar metabolic pressures on the gut microbiome across populations, potentially affecting host nutrient availability and immune responses in a predictable manner. Discussion and ConclusionThis study provides robust evidence that T. trichiura infection induces significant and consistent microbiome alterations across diverse populations. The depletion of SCFA-producing bacteria and the enrichment of mucin-degrading taxa, along with corresponding metabolic pathways, imply compromised gut barrier integrity, providing insights into the complex inflammatory processes associated with this helminth infection. Additionally, these microbiome differences could play a critical role in facilitating parasite persistence and reinfection, which remain major challenges limiting the efficacy of global control strategies. Our findings highlight the potential of microbiome-targeted interventions, such as probiotic supplementation or dietary modifications, to mitigate the health impacts of T. trichiura infections by restoring microbial homeostasis.

Source connections

Explore related subjects

Keep this discovery

Explore connections, maps & timelines

BibTeXRIS

Schneeberger, P. H. H., Dommann, J., Rahman, N. O., Huerlimann, E., Sayasone, S., Ali, S. M., Coulibaly, J. T., keiser, J.. 2025-03-24. Profound taxonomic and functional gut microbiota alterations associated with trichuriasis: cross-country and country-specific patterns. https://doi.org/10.1101/2025.03.21.641387

Cite the original work for its findings. Save a collection to share your selection of sources.

KEEP EXPLORING

Related preprints

pTRIP, a novel integration plasmid for Listeria monocytogenes

In the past decades, several tools to genetically modify the human pathogen Listeria monocytogenes were developed. Here, we constructed a new integrative plasmid system for L. monocytogenes named pTRIP, for treB insertion plasmid. pTRIP is a vector which stably integrates into the treB locus of the wild type EGD-e. This locus encodes the sole trehalose-specific EIIB and EIIC component of a phosphotransferase system. Successful integration leads to the disruption of treB and thus, to an inability of the resulting L. monocytogenes strains to grow on trehalose as sole carbon source. Due to integration through double homologous recombination, it is the first integrative system which does not require antibiotic selection pressure. To assess functionality of the pTRIP system, prfA and its native promoter region were integrated into the treB locus of a {Delta}prfA strain. Complementation was confirmed in 78% of the isolated clones, indicating successful integration of prfA into the treB locus. We further constructed derivatives of pTRIP harboring the constitutive Pp60 (pTRIP1) and the inducible Prha (pTRIP2) promoter to further expand application possibilities. Microscopic analyses confirmed the functionality of both promoter constructs and showed dose-dependent induction for Prha. pTRIP is an efficient tool for stable gene expression as well as functional studies and expands genetic modification possibilities for L. monocytogenes.

microbiology↗

A rational design strategy and validation for protease-resistant fusion-inhibitor antiviral peptides

Peptide-based fusion inhibitors are promising pharmaceuticals in the fight against enveloped viruses relying on membrane fusion for host infection. However, peptide therapeutic applications have long been hindered by their poor stability in vivo. Here, we discovered that peptide inhibitors with the wildtype sequence of the heptad repeat 2 (HR2) domain of the SARS-CoV-2 spike protein are efficiently cleaved by Transmembrane Protease, Serine 2 (TMPRSS2), a key protease involved in the SARS-CoV-2 virus-cell fusion pathway. We then identified the corresponding cleavage sites and designed three protease-resistant peptides using ranking based on deep mutational scanning and natural occurrence. The three candidates all exhibit inhibitory activity in a cell-cell fusion assay. A high-resolution cryo-EM structure of the top candidate, HR2-NHN, bound to its HR1 target reveals the molecular basis for its potent activity. The top candidate of the cell-based screening assay significantly improved efficacy relative to the wildtype peptide when administered 12 h before infection in both an authentic virus-cell infection assay and a mouse assay. More broadly, our results suggest that the design strategies for protease-resistant peptides could be applied to a broad spectrum of other enveloped viruses and pave the way for the development of safe, prophylactic antivirals that can be administered before exposure.

microbiology↗

Host soluble inositol phosphate signaling promotes coronavirus replication

Coronaviruses rely extensively on host pathways for replication, making host-directed therapies an attractive strategy for broad-spectrum antivirals with reduced risk of viral resistance. Here we identify the host soluble inositol phosphate pathway as a previously unrecognized dependency for coronavirus infection. Genetic or pharmacologic inhibition of several kinases in this pathway markedly suppresses replication of both alpha- and betacoronaviruses, while increasing pathway activity promotes viral replication. We developed UNC7844, a potent multi-target inhibitor of these kinases, which reduces coronavirus replication by more than four orders of magnitude in cultured cells and suppresses coronavirus infection in mice. Mechanistically, UNC7844 suppresses inositol (pyro)phosphates production, disrupts phosphoinositide homeostasis, and impairs late endosomal dynamics, blocking early post-entry steps required for viral genome release and replication. Together, our findings establish the soluble inositol (pyro)phosphate pathway as an important regulator of coronavirus infection and highlight its inhibition as a promising host-directed antiviral strategy.

microbiology↗