Compromised intestinal barrier underlies gut microbiota dysbiosis of intestinal diseases

Despite recent efforts, a single factor underlying the gut microbiota dysbiosis in intestinal diseases is not identified. We hypothesized that compromised intestinal barrier (CIB) could lead to increased host-derived contents including human cells in the gut, change its physio-metabolic properties, and globally alter gut microbiota and their metabolic capacities. Consistently, we found human DNA contents (HDCs), calculated as the percentage of metagenomic sequencing reads mapped to the human genome, were significantly elevated in colorectal cancer (CRC) patients; HDC correlated with microbial- and metabolic-pathway-biomarkers of CRC, and was the most important contributor to patient stratification. We found similar results in Crohn9s disease (CD); additionally, patients treated with diet and drug intervention showed reduced HDC levels over time, and were accompanied by reversing changes of many CD-signature species. Our results suggested that host-derived contents may have greater impact on gut microbiota than previously anticipated, and CIB could be an ideal treatment target that could reverse dysbiosis globally and precisely.