The gut microbiome exhibits marked spatial heterogeneity across gastrointestinal segments (e.g., stomach, duodenum, colon), with distinct microbial compositions and metabolic functions influencing host metabolism and immunity. Traditional fecal-centric approaches overlook this regional specificity, limiting insights into diseases like diabetes, metabolic-associated steatotic liver disease (MASLD), and functional constipation. For instance, small intestinal bacterial overgrowth (SIBO) disrupts bile acid metabolism by prematurely deconjugating bile acids in the duodenum, impairing their signaling via receptors (e.g., FXR, TGR5) and exacerbating metabolic dysregulation. Similarly, oral microbiota translocating to the lower gut may drive immune dysregulation, as seen in Graves’disease
Key findings from the study include:

1. ​​Region-Specific Microbial Dynamics Drive Metabolic Dysregulation​​:The duodenum and colon exhibit distinct microbial profiles with disease-specific impacts. For example, duodenal small intestinal bacterial overgrowth (SIBO) disrupts bile acid metabolism, exacerbating obesity and diabetes. Oral microbiota (e.g., Streptococcus) translocating to the colon triggers immune dysregulation, linked to autoimmune conditions like Graves’ disease.
2. Geographic and Dietary Shaping of Microbial Ecosystems​​:Gut microbiota in China shows marked geographic variation: Northeast China’s cold climate enriches Lachnospiraceae (producers of short-chain fatty acids), while Southern China’s rice-based diet correlates with Lactococcus and Fusobacterium dominance. Wheat consumption in Northern China promotes Bifidobacterium, influencing lipid metabolism.
3. Core Microbial Guilds as Therapeutic Targets:​​A conserved "core" microbiome (Bacteroides, Clostridium) governs fiber fermentation and butyrate synthesis. Dysbiosis in this core—e.g., reduced Oscillospira (butyrate producer) and enriched Alistipes in constipation—impairs gut motility and barrier function. Probiotics (e.g., Clostridium clusters) and dietary fiber restore balance, alleviating metabolic syndrome.
4. Innovative Interventions and Diagnostic Potential​​:

Mechanical​​: Duodenal mucosal resection (DMR) reduces SIBO by removing biofilms.
AI-Driven​​: Machine learning integrates multi-omics data to predict microbial dynamics for personalized therapies.
Diagnostic​​: Oral microbiota translocation signatures (e.g., Streptococcus) and bile acid receptor expression serve as biomarkers for autoimmune and metabolic disorders

This study highlights the ​​critical role of region-specific gut microbial distribution​​ in metabolic and immune regulation. Key mechanisms include duodenal SIBO-driven bile acid disruption, geographic/dietary influences on microbial networks (e.g., Lachnospiraceae in Northeast China), and dysbiosis in core fiber-degrading guilds. Innovations like DMR, probiotics, and AI-driven models offer precision therapies, while translocated oral microbiota (e.g., Streptococcus) provide diagnostic biomarkers. However, challenges persist: geographic variability (e.g., underrepresented African populations) and functional redundancy (e.g., competing microbial guilds) complicate universal solutions. Mapping microbial spatial dynamics is essential for advancing personalized medicine. The work entitled “Investigating regional-specific gut microbial distribution:an uncharted territory in disease therapeutics” was published on Protein & Cell (published on Oct. 29, 2024).
DOI：https://doi.org/10.1093/procel/pwae058