Mucosal Hub Bacteria as Potential Targets for Improving High-Fat Diet-Related Intestinal Barrier Injury

Background: Intestinal barrier injury contributes to multiple diseases such as obesity and diabetes, whereas no treatment options are available. Methods: Due to close interactions between mucosal microbiome and intestinal barrier, we evaluated the potential of mucosal bacteria in providing targets for high-fat diet (HFD)-related intestinal barrier injury. Whole-genome metagenomics was used to evaluate mucosal microbiome, while intestinal barrier injury was estimated using serum LPS, FITC-dextran intensity, and ZO-1 protein. Results: We found that HFD induced significant fat accumulation in epididymal tissue at weeks 4 and 12, while ALT, LDL, and TC increased at week 12. Intestinal barrier injury was confirmed by elevated serum LPS at both weeks, upregulated FITC-dextran intensity, and decreased ZO-1 protein at week 12. Fourteen species such as Phocaeicola vulgatus differed in HFD-fed mice. The co-occurrence network of mucosal microbiome shifted from scale-free graph in controls to nearly random graph in HFD-fed mice. Besides, 10 hub bacteria especially Bacteroides ovatus decreased drastically in both mucosal and fecal samples of HFD-fed mice, correlated with intestinal permeability, ALT, and KEGG pathways such as "Mitochondrial biogenesis" and "metabolism". Moreover, Bacteroides ovatus has been confirmed to improve intestinal barrier function in a recent study. Conclusion: Mucosal hub bacteria can provide potential targets for improving HFD-related intestinal barrier function.