Whipworm infection remodels the gut microbiome ecosystem and compromises intestinal homeostasis in elderly patients revealed by multi-omics analyses

Benguang Zhang^1,2,3Zhaoan Sheng⁴Cancan Bu²Longjiang Wang²Wenxiang Lv²Yongbin Wang²Yan Xu²Ge Yan²Maoqing Gong^2*Lijuan Liu^2*Wei Hu^5,6,7*

• ¹State Key Laboratory of Genetic Engineering, Ministry of Education Key Laboratory for Biodiversity Science and Ecological Engineering, School of Life Science, Fudan University, Shanghai, China
• ²Shandong Institute of Parasitic Diseases, Shandong First Medical University & Shandong Academy of Medical Sciences, Jining, China
• ³School of Public Health, Shandong First Medical University & Shandong Academy of Medical Sciences, Jning, China
• ⁴Department of Pathogenic Biology, Jining Medical University, Jning, China
• ⁵State Key Laboratory of Genetic Engineering, Ministry of Education Key Laboratory of Contemporary Anthropology, School of Life Science, Fudan University, Shanghai, China
• ⁶State Key Laboratory of Reproductive Regulation and Breeding of Grassland Livestock, School of Life Sciences, Inner Monglia University, Hohhot, China
• ⁷Prevention (Chinese Center for Tropical Diseases Research),National Center for International Research on Tropical Diseases, Ministry of Science and Technology, Shanghai, China

Whipworm (Trichuris trichiura) coexists with symbiotic microbiota in the gastrointestinal ecosystem. There is a paucity of data on the association between whipworm infection and the gut microbiota composition in elderly individuals. This study was designed to investigate changes in gut microbiota and function and its metabolite profile in patients with whipworm infection. Hence, we used 16S rRNA gene sequencing to identify microbial signatures associated with whipworm infection.Subsequently, shotgun metagenomic sequencing revealed functional changes that highlighted disruptions in microbial gene expression and metabolic pathways influencing host health. Ultraperformance liquid chromatography-mass spectrometry metabolomics was used to characterize whipworm infection-induced metabolic perturbations and elucidate metabolite dynamics linked to microbial activity.Collectively, this multi-omics approach deciphered structural, functional, and metabolic remodeling of the gut ecosystem that distinguished whipworm-infected patients from healthy controls. Analyses of the gut microbiome in patients with whipworm infection revealed significantly increased observed species richness and ACE indices, along with an enrichment of Prevotella 9-driven enterotypes.Additionally, metagenomic and metabolomic analyses indicated enrichment in metabolic pathways related to amino acid, energy, and carbohydrate metabolism.Metabolic network analysis further suggested that the upregulated Prevotella copri and Siphoviridae sp. were positively correlated with elevated levels of myristic acid and DL-dipalmitoylphosphatidylcholine. These findings suggest that whipworm 4 infection significantly remodels the gut microbiome ecosystem and compromises intestinal homeostasis.