Gut biogeographical microbiome in dyspepsia links duodenal ecology and opportunistic pathogens with plasma biomarkers

Dysbiosis of dyspepsia-associated microbiome gradients remains poorly understood across gastrointestinal biogeography. This study evaluates a prospective, dyspeptic cohort of 121 subjects from a tertiary care centre in India, using full-length Oxford Nanopore amplicon sequencing of 16S rDNA and ITS region of its bacteriome and mycobiome, respectively. Anatomically distinct bacteriome (PERMANOVA R 2 > 40%) and a less varying sparse mycobiome (R 2 = 9%) were observed among 246 samples spanning saliva, duodenal mucosa and stool. Oral and duodenal cores shared opportunistic pathogens like pro-inflammatory Streptococcus milleri group (SMG), with Helicobacter pylori and Serratia marcescens uniquely detected in duodenal mucosa. Integrating plasma biomarkers of upper-gut health (Pepsinogen I/II, Gastrin-17b, Zonulin) revealed biochemical perturbation-linked shifts in duodenal and fecal communities. An increase of Streptococcus species in duodenal mucosa under abnormal Pepsinogen and Gastrin gradients was noted, while the presence of H. pylori in the duodenum was associated with differential community diversity. The patterns of disordered state-specific dysbiosis scores and machine-learnt models for junctional duodenum and accessible saliva/stool samples further accentuate the understanding of microbiome-based risk assessment of upper gut disorders.