Traditional Chinese Medicine: An Exogenous Regulator of Crosstalk between the Gut Microbial Ecosystem and CKD

Abstract

Chronic kidney disease (CKD) is often accompanied by an imbalance in the gut microbial ecosystem. Notably, the imbalanced gut microbiota and impaired intestinal barrier are the keys to the crosstalk between the gut microbial ecosystem and CKD, which was the central point of previous studies. Traditional Chinese medicine (TCM) has shown considerable efficacy in the treatment of CKD. However, the therapeutic mechanisms have not been fully elucidated. In this review, we explored therapeutic mechanisms by which TCM improved CKD via the gut microbial ecosystem. In particular, we focused on the restored gut microbiota (i.e., short-chain fatty acid- and uremic toxin-producing bacteria), improved gut-derived metabolites (i.e., short-chain fatty acid, indoxyl sulfate, p-Cresyl sulfate, and trimethylamine-N-oxide), and intestinal barrier (i.e., permeability and microbial translocation) as therapeutic mechanisms. The results found that the metabolic pattern of gut microbiota and the intestinal barrier were improved through TCM treatment. Moreover, the microbiota-transfer study confirmed that part of the protective effect of TCM was dependent on gut microbiota, especially SCFA-producing bacteria. In conclusion, TCM may be an important exogenous regulator of crosstalk between the gut microbial ecosystem and CKD, which was partly attributable to the mediation of microbiota-targeted intervention.

Perspective on the Modern Interpretation of the Property Theory of Mild-natured and Sweet-flavored Traditional Chinese Medicine via Gut Microbiota Modulation

“…[57] Generally, CKD is accompanied by higher levels of urinary toxins, oxidative stress, inflammation, and a destroyed intestinal barrier. [58] Urotoxins mainly consist of endogenous, exogenous, and enterogenous endotoxins. Enterogenous endotoxins are produced by the gut microbiota, and are mainly included indoxyl sulfate (IS), p-cresyl sulfate, trimethylamine-N-oxide (TMAO).…”

“…Enterogenous endotoxins are produced by the gut microbiota, and are mainly included indoxyl sulfate (IS), p-cresyl sulfate, trimethylamine-N-oxide (TMAO). [58,59] The families Clostridiaceae, Enterobacteriaceae, Pseudomonadaceae, and Bacteroidiaceae are some of the bacteria that can produce enterogenous endotoxins and are enriched in patients with CKD. [60] Therefore, urinary toxins can be attenuated by regulating the gut microbiota.…”

“…For example, SCFAs can activate GPR41, promote CD4 T cells, and innate lymphoid cells to produce IL-22, which further increases the expression of tightly connected cells to repair the intestinal barrier. [58] Dioscoreae Rhizoma and F. lycii can upregulate SCFA-producing bacteria such as Clostridium , Akkermansia , and Turicibacter , [49] thereby playing a role in kidney disease. Furthermore, the NF-κB pathway could promote TMAO production, implying that the inhibition of TLR-4/MYd88/NF-κB or downregulation of LPS-producing bacteria can also inhibit the production of endotoxins.…”