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Objective Transient receptor potential vanilloid 4 (TRPV4), a non-selective cation channel, is deeply involved in the physiological and pathological regulation of multiple organ systems, while the comprehensive influencing mechanism of its mutation on animal intestines and intestinal flora is not clear. This study explored the regulatory effects of Trpv4 exon 8 c.1491+1G>A mutation on intestinal barrier integrity and flora-metabolic microenvironment in mice, aiming to provide an experimental basis for analyzing the interaction mechanisms between host genes and intestinal flora. Methods Trpv4 exon 8 c.1491+1G>A gene-edited mice previously constructed in our laboratory were taken as the research objects, and the expression levels of Trpv4 and TRPV4 in the intestinal tissue were determined by qPCR and Western blotting, respectively. Pathological sections were prepared for observation of the structural changes of the intestinal tissue. The 16S rRNA gene high-throughput sequencing was conducted to reveal the structural differences of intestinal flora. Non-targeted metabolomics based on LC-MS was employed to examine the changes of fecal metabolites, and the correlations between flora and metabolites were analyzed. Results Trpv4 editing led to the abnormal expression of Trpv4 and TRPV4 in the intestinal tissue of mice, which resulted in the structural abnormality of the intestinal tissue and the impairment of intestinal barrier function. In addition, the gene-edited mice exhibited an imbalance in intestinal flora, with significantly increased relative abundance of Bacteroidota, a significantly decreased Bacillota/Bacteroidota (F/B) ratio, and reduced abundance of common commensal bacteria such as Staphylococcus. Metabolomic analysis indicated that the gene-edited mice presented disordered lipid metabolism and abnormalities in immune-related metabolites. The abundance of Bacteroidota was positively correlated with lipid metabolites, while that of Desulfovibrio and Enterobacter was negatively correlated with lipid and immune metabolites. Conclusion Trpv4 exon 8 c.1491+1G>A gene-edited mice exhibited impaired intestinal barrier function, along with alterations in intestinal flora structure and the metabolic microenvironment. This study provides basic data for elucidating the interactions between specific gene mutations and the gut microbiota and offers theoretical support for the development of diagnostic and therapeutic strategies for Trpv4-related diseases.
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| 科 Family | 属数 Number of genus | 种数 Number of species | 占总种数比例 Percentage of total species (%) | 属 Genus | 种数 Number of species | 占总种数比例 Percentage of total species (%) |
|---|---|---|---|---|---|---|
| 鹅膏菌科Amanitaceae | 2 | 11 | 5.26 | 鹅膏菌属 Amanita | 10 | 4.78 |
| 小菇科 Mycenaceae | 2 | 12 | 5.74 | 丝盖伞属 Inocybe | 5 | 2.39 |
| 多孔菌科 Polyporaceae | 8 | 14 | 6.70 | 蜡蘑属 Laccaria | 5 | 2.39 |
| 红菇科 Russulaceae | 3 | 23 | 11.00 | 小皮伞属 Marasmius | 6 | 2.87 |
| 小菇属 Mycena | 11 | 5.26 | ||||
| 光柄菇属 Pluteus | 5 | 2.39 | ||||
| 红菇属 Russula | 17 | 8.13 | ||||
| 栓菌属 Trametes | 5 | 2.39 |
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