Gut microbial diversity and candidate keystone taxa in Indian tribes: Insights across lifestyle-ecological continuum and health associations.

Primary biliary cholangitis (PBC), previously termed primary biliary cirrhosis, is a chronic autoimmune disease that predominantly affects middle-aged women []. It is characterized histologically by chronic nonsuppurative destruction of the intrahepatic small bile ducts and clinically by cholestasis, and progressive liver dysfunction. Serologically, PBC is associated with elevated alkaline phosphatase (ALP) levels, γ-glutamyl transpeptidase (GGT) levels, and the presence of antimitochondrial antibodies (AMA) []. Accumulating evidence supports a substantial genetic contribution to PBC susceptibility. Familial aggregation, increased risk among first-degree relatives, and high concordance rates in monozygotic twins indicate a heritable component underlying disease development [–]. Genome-wide association studies (GWAS) have identified multiple risk loci involved in PBC [–]; however, these variants generally confer modest effect sizes and do not fully explain disease heritability. In contrast, rare germline variants with larger functional effects may play a critical role in familial PBC, yet such variants remain poorly characterized. Whole-exome sequencing provides an effective approach for identifying rare, potentially pathogenic variants in multiplex families [], but its application in familial PBC has been limited, and functional validation of candidate variants in vivo is scarce.