Distinct Spatial Variations of Gastrointestinal Microbiome and Its Associated Inflammatory Pathogenesis under Simulated Microgravity (PRJCA043003)

Gastrointestinal microbiota exhibits intricate spatial stratification critical for regional functionality, yet the compartment-specific microbial dynamics under simulated microgravity (SMG) remain poorly resolved. Conventional reliance on fecal or colonic analysis inadequately captures dysbiotic patterns in proximal niches, particularly the ileum, a pivotal site for immune regulation and barrier integrity. Here, we employ region-resolved sampling (stomach, jejunum, ileum, colon, feces) and multimodal analytics in a rodent SMG model to dissect microbial biogeography and its pathophysiological sequelae. 16S rRNA sequencing revealed pronounced ileal dysbiosis under SMG, characterized by enrichment of pathobionts (Klebsiella, Escherichia_Shigella) and depletion of butyrogenic Oscillospiraceae, contrasting with resilient colonic communities. Functional profiling via PICRUSt revealed ileum-specific enrichment of mucin-degrading enzymes (e.g., L-fucose dehydrogenase) and oxidative stress pathways, whereas bioorthogonal near-infrared (NIR) imaging confirmed SMG-induced macroscopic changes of intestinal bacterial density and distribution. Compartmental histopathology corroborated ileal barrier disruption, marked by goblet cell loss, microvillar atrophy, and elevated proinflammatory cytokines. Crucially, fecal microbiota failed to reflect the ileal perturbations, underscoring the non-equivalence of distal and proximal microbial landscapes. Mechanistically, SMG stress-caused ileal dysbiosis paralleled inflammatory bowel disease-like trajectories, with lipooligosaccharide transport pathways amplifying endotoxemia and paracellular permeability. These findings establish the ileum as a vulnerable epicenter of microgravity-associated enteropathy and advocate for region-specific microbiota monitoring in health protocols of space flight.