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Generation, Maintenance, and Identification of Germ-Free Zebrafish Models from Larvae to Juvenile Stages

Zebrafish serve as valuable models for research on growth, immunity, and gut microbiota due to their genomic similarities with mammals, transparent ...

Chongqing Medical University

Traditional herbal medicine (THM) is used worldwide for its safety and effectiveness against various diseases. Huoxiang Zhengqi (HXZQ) is an extensively used Chinese THM formula targeting gastrointestinal disordered gastroenteritis  regulating the intestinal microbiome/immuno-microenvironment. However, the specific mechanisms remain largely unexplored, besides as a lifestyle drug, its safety on the gut microbiome homeostasis has never been investigated. In this study, the effects of HXZQ on the gut microbiome of healthy adults were investigated for the first time, and the antibiotic-induced gut microbiota dysbiosis mice model was applied for verification. Based on healthy adults, our results revealed that HXZQ exhibited mild and positive impacts on the bacterial diversity and the composition of the gut microbiome in a healthy state. As for an unhealthy state of the gut microbiome (with low bacterial diversity and deficient compositions), HXZQ significantly restored the bacterial diversity and recovered the abundance of . In the antibiotic-induced mice model, HXZQ distinctly revived the deficient gut microbial compositions impaired by antibiotics. At the genus level, the abundances that responded most strongly and positively to HXZQ were  in healthy adults and , , and  in mice. In contrast, the abundance of  in healthy adults, , and  in mice showed inversely associated with HXZQ administration. At last, HXZQ might exhibit an anti-inflammatory effect by regulating the concentration of interleukin-6 in plasma while causing no significant changes in the colon tissue structure in mice. In conclusion, our results elucidate that the safety of HXZQ in daily use further reveals the modulatory effects of HXZQ on gut microbial community structure. These results will provide new insights into the interaction of THM and gut microbiome homeostasis and clues about the safe use of THM as a lifestyle drug for its further development.

Modulatory Effects of Huoxiang Zhengqi Oral Liquid on Gut Microbiome Homeostasis Based on Healthy Adults and Antibiotic-Induced Gut Microbial Dysbiosis Mice Model.

Prodigiosin (PG) is a secondary metabolite of microorganisms with anticancer, antimalarial, antibacterial and immunomodulatory effects. However, the modulatory effects on gut microbiome and intestinal immune microenvironment have never been explored in the ulcerative colitis (UC) mice model. In this study, 2.5% dextran sulfate sodium (DSS) induced UC mice model was constructed to investigate the effects of PG derived from a chromium-resistant Serratia sp. on the intestinal flora and inflammatory response. The results showed that prodigiosin administration attenuated the DSS-induced UC symptoms, including preventing the reduction of colonic length and DSS-induced mortality. Furthermore, prodigiosin ameliorated the DSS-induced gut microbiota community dysbiosis by restoring the abundance of Bacteroidota. At the genus level, the declined abundance of Bifidobacterium, Allobaculum and Akkermannia in UC mice was elevated by the treatment of PG. Pathological results by H&E staining showed that PG prevented the appearance of distortion and atrophy of crypt and neutrophil infiltration in a dose-dependent manner. RT-PCR revealed that the expression levels of the inflammatory factors IL-1β, IL-6 and IL-10 were significantly suppressed, and the expression of the intestinal tight junction protein Claudin-1, Occludin and ZO-1 were upregulted in PG-treated UC mice. Conclusively, our results revealed that prodigiosin effectively prevented inflammatory response and protected intestinal barrier integrity of DSS-induced colitis mice via modulating gut microbiota community structure, suppressing inflammatory factors' expression, and accelerating the expression of intestinal tight junction protein. These results will provide new insights into the interaction of prodigiosin with intestinal microbiota homeostasis and its application in clinical against inflammatory bowel disease.

Prodigiosin derived from chromium-resistant Serratia sp. prevents inflammation and modulates gut microbiota homeostasis in DSS-induced colitis mice.

 is known for forming bacterial biofilms that confer increased antimicrobial resistance. Combining antibiotics with antibiofilm agents is an alternative approach, but the antibiofilm ability of prodigiosin (PG), a potential antibiotic synergist, against antimicrobial-resistant (AMR)  remains to be understood. The antibiofilm activity of PG against 29 clinical AMR  strains was evaluated using crystal violet staining, and its synergistic effects with vancomycin (VAN) was confirmed using the checkerboard test. The viability and metabolic activity of biofilms and planktonic cells were also assessed. The results revealed that PG exhibited promising inhibitory activity against biofilm formation and synergistic activity with VAN. It effectively reduced the metabolic activity of biofilms and suppressed the production of exopolysaccharides, which might be attributed to the downregulation of biofilm-related genes such as , , and . These findings suggest that PG could be used as a preventive coating or adjuvant against biofilms in clinical settings.

Article	Year
Modulatory Effects of Huoxiang Zhengqi Oral Liquid on Gut Microbiome Homeostasis Based on Healthy Adults and Antibiotic-Induced Gut Microbial Dysbiosis Mice Model. Frontiers in pharmacology\| PubMed ID: 35401199	2022
Prodigiosin derived from chromium-resistant Serratia sp. prevents inflammation and modulates gut microbiota homeostasis in DSS-induced colitis mice. International immunopharmacology\| PubMed ID: 36780827	2023
Prodigiosin as an antibiofilm agent against multidrug-resistant . Biofouling\| PubMed ID: 37369552	2023

Xiang-Ru Liu

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