Combined 1H NMR fecal metabolomics and 16S rRNA gene sequencing to reveal the protective effects of Gushudan on kidney-yang-deficiency-syndrome rats via gut-kidney axis

May 27, 2022Journal of pharmaceutical and biomedical analysis

Gut and feces analysis show Gushudan may protect kidney function in rats with kidney-yang deficiency

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Abstract

Gushudan (GSD) significantly regulated the levels of 12 out of 31 potential metabolites in kidney-yang-deficiency-syndrome (KYDS) rats.

GSD is associated with changes in the abundance of 11 out of 16 potential microbial biomarkers related to KYDS.
Fecal metabolomics indicated that GSD may normalize abnormal levels of gut microbial-mediated metabolites such as tryptophan and butyrate.
GSD could promote the growth of beneficial bacteria, including those that produce butyrate and lactate.
Altered fecal metabolites showed strong correlations with changes in intestinal microflora at the genus level.
The findings support the concept of a gut-kidney axis in understanding KYDS and evaluating the efficacy of GSD.

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Based on traditional Chinese medicine (TCM) theory, kidney is regarded as governing the bones and dominating the storage of essence ('jing' in Chinese). Gushudan (GSD) is a traditional Chinese medicine prescription with the effects of strengthening bone and nourishing kidney, which has been used to treat osteoporosis for years. Several anti-osteoporosis effects of GSD have been investigated based on metabolomics in previous studies. However, the specific mechanism of GSD on kidney tonifying and its alterations in gut microbiota are still unclear. In this study,H NMR fecal metabolomics and 16 S rRNA gene sequencing technology were integrated to comprehensively explore the microbiota and metabolic changes in kidney-yang-deficiency-syndrome (KYDS) rats and to elucidate the protective mechanism of GSD through the gut-kidney axis. GSD significantly regulated the levels of 12 out of 31 potential metabolites and the abundance of 11 out of 16 potential microbial biomarkers related to KYDS, respectively. Fecal metabolomics showed that GSD could reserve the abnormal levels of gut microbial-mediated metabolites of KYDS rats, such as tryptophan, lysine, dimethylamine, creatinine, acetate and butyrate, which mainly involved in amino acid metabolism, methylamine metabolism, energy metabolism and short-chain fatty acid metabolism. Specifically, GSD could promote butyrate-producing bacteria g_Lachnospiraceae_NK4A136_group and lactate-producing bacteria g_Lactobacillus. Interestingly, there was a strong relationship between altered fecal metabolites and perturbed intestinal microflora in genus. For example,lysine was negatively correlated with g_Lactobacillus, while acetate was positively correlated with g_Barnesiella. In conclusion, the study showed that the gut-kidney axis had scientific implications, which not only offered new insights into the in-depth understanding of the pathogenesis of KYDS, but also provided further evidence for the efficacy evaluation of GSD. 1

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Combined 1H NMR fecal metabolomics and 16S rRNA gene sequencing to reveal the protective effects of Gushudan on kidney-yang-deficiency-syndrome rats via gut-kidney axis

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