keiser, J. | bioRxiv Science

bioRxiv2025

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

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.

microbiology↗

bioRxiv2024

The assessment of single nucleotide polymorphisms in the ss-tubulin genes in human soil-transmitted helminths exposed to different pressure with benzimidazole drugs

BackgroundWe aimed to gain insights into the role of known single nucleotide polymorphisms (SNPs) in codons 167, 198 and 200 of the {beta}-tubulin gene as markers for possible benzimidazole resistance in human soil-transmitted helminths (STHs; Ascaris lumbricoides, Trichuris trichiura, Necator americanus and Ancylostsoma duodenale). MethodsFirstly, we determined the analytical performance of our PCR/pyrosequencing assays. Secondly, we applied them on stool samples collected during clinical trials in Ethiopia, Lao PDR, and Pemba Island (Tanzania) to assess any associations between the presence/ratio of mutant (MT): wild type (WT) SNPs and drug pressure history, individual drug response and time of sampling (baseline vs. follow-up sample). Principal findingsOverall, the limit of blank of our in-house PCR/pyrosequencing assays to detect MT SNPs was non-zero ([~]3.5%), and hence the limit of detection for MT SNPs was relatively high (2% - 7%). The assays systematically overestimated the true underlying ratio of MT:WT SNPS within sample, but we derived functions for more accurate estimates. The assays were more precise when the ratio MT:WT SNPs was high (>5%). No PCR amplicon was observed in 25% of the samples subjected to PCR. In the remaining samples, the presence of MT SNPs in codon 200 was detected in half of the analysed Trichuris samples, the proportion of the analysed samples containing MT SNPs did not exceed 14% for all other codons and STH species. Associations between drug pressure history, individual drug response and time of sampling, were not consistent across all codons and STHs. ConclusionWe could not provide compelling evidence for the role of the known SNPs in the {beta}-tubulin gene as markers for benzimidazole resistance. Our study also highlights that there is a need to assess the diagnostic performance of any assays in order to readily interpret and compare results. Further research should therefore also focus on genes other than the {beta}-tubulin genes. Author summaryAlthough large-sale deworming programs are reducing the morbidity caused by intestinal worms, widespread treatment of large populations for a long period of time may trigger drug resistance. An early detection of DNA mutations that may give rise to resistant worm population is therefore important. We evaluated the analytical performance of in-house assays to detect DNA mutations that are known to cause resistant intestinal worms of animals. Subsequently, we applied these assays on stool samples to verify (i) whether the mutations are more prevalent in areas were large proportions of children have been dewormed for a longer period, (ii) a poor individual drug response can be explained by higher frequency of the mutations. Our results indicate that comprehensive evaluation of the analytical performance of the genotyping tests was required to readily interpret the results. We did not find any compelling evidence that the presence of mutations was associated with either drug pressure or poor individual drug responses. This suggests that it is warranted to explore other mutations than those documented in animal worms.

molecular biology↗