Changes in the abundance of the fecal microbiota are implicated in the pathogenesis of diarrhea in yak calves

The yak, a species of considerable economic importance on the Qinghai-Tibet Plateau, encounters a substantial challenge in the form of diarrhea during its calf stage. However, research on diarrhea in yak calves remains limited. Considering the strong association between diarrhea and intestinal microbiota, this study conducted an analysis of the fecal microbiota composition in both diarrheic and healthy yak calves. Additionally, a pseudo-germ-free (PGF) mouse model was employed to investigate the causes of diarrhea. This study elucidated the presence of microbial dysbiosis in diarrheic yak calves, marked by a significant enrichment of Ruminococcus gnavus ( R. gnavus ) and Streptococcus . An elevation in serum pro-inflammatory factors was observed in the diarrheic calves. Notably, the relative abundances of R. gnavus and Streptococcus exhibited a positive correlation with serum levels of IL-12p70 and KC/GRO. In PGF model, the anal infusion of fecal filtrate derived from diarrheic calves resulted in colonic damage and inflammation. KEGG pathway analysis indicated an enrichment of the inflammatory bowel disease pathway, with upregulation of transcription factors such as TNF , IFIT2 , IL-1α , CXCL9 , NOS2 , STAT1 , IRGM1 , CXCL11 , ISG15 , and USP18 in the colonic mucosa of the D-FMT group (anal infusion of fecal filtrate from diarrheic yak calves). Metabolomic analysis identified 43 upregulated metabolites in the D-FMT group, predominantly associated with metabolic pathways and aldosterone synthesis and secretion. Importantly, Bisphenol AF in the colonic contents demonstrated a positive correlation with the transcription factors TNF , IFIT2 , IL-1α , CXCL9 , and NOS2 . This study identified R. gnavus and Streptococcus as potentially pathogenic bacteria contributing to diarrhea. Furthermore, Bisphenol AF was identified as a metabolite significantly elevated after FMT from diarrheic donors, which may be involved in colonic inflammatory signaling. These findings provide a foundation for the development of microbiota-based diagnostic tools or preventive strategies to address diarrhea in yak calves on the Qinghai-Tibet Plateau.