Rhubarb Enema Increasing Short-Chain Fatty Acids that Improves the Intestinal Barrier Disruption in CKD May Be Related to the Regulation of Gut Dysbiosis

Abstract

The incidence of CKD seriously endangers people’s health. Researchers have proposed that improving the intestinal barrier damage in CKD may be an effective target for delaying the progression of CKD. Rhubarb can effectively improve the intestinal barrier and renal fibrosis, which may be related to the regulation of gut dysbiosis, but the mechanism needs to be further studied. Short-chain fatty acids (SCFAs) are important metabolites of the gut microbiota and play an important role in maintaining the intestinal barrier. The purpose of this study was to investigate whether rhubarb enema regulates the production of short-chain fatty acid-related gut microbiota and improves the intestinal barrier damage of CKD. 5/6 nephrectomy rats were used as the animal model, sevelamer was used as the positive control group, and the sham operation rats were used as the control group. After 4 weeks of enema treatment, the general clinical indicators, short-chain fatty acid levels, renal pathology, intestinal tissue pathology, intestinal tight junction protein, and changes in gut microbiota were detected. The results showed that rhubarb enema can increase the level of short-chain fatty acids in the 5/6 nephrectomy model rats, improve the intestinal barrier damage, inhibit the decrease of intestinal tight junction proteins, reduce inflammation levels, improve kidney pathology, reduce blood creatinine levels, and regulate the intestinal tract, the abundance, and composition of the flora. Further correlation analysis showed that rhubarb enema increased the level of short-chain fatty acids in 5/6 nephrectomy model rats, which may be related to the 7 strains that may regulate the production of short-chain fatty acids. This study indicated that rhubarb enema can improve the intestinal barrier damage of 5/6 nephrectomy model rats and improve CKD, which may be related to the regulation of short-chain fatty acid-producing gut microbiota.

The modulation effects of plant‐derived bioactive ingredients on chronic kidney disease: Focus on the gut–kidney axis

“…SCFAs show many positive regulatory functions, including serving as a major energy source for colonocytes (Vaziri et al., 2016), immunomodulation (Koh et al., 2016), enhancing gut barrier integrity and function (G. Chen et al., 2018; Ramezani et al., 2016), promoting the production of gut hormones (Iwasaki et al., 2019), improving metabolic health (Morrison & Preston, 2016), and especially slowing the progression of CKD (H. Zhu et al., 2021). An experiment of 5/6 nephrectomy model rat experiment revealed that gut bacteria producing SCFAs could improve kidney pathology and regulate intestinal tight junction proteins (Ji et al., 2022). According to the recent studies, SCFAs demonstrated a protective role against acute tubular injury from inflammation (Corrêa‐Oliveira et al., 2016) by means of inhibiting HDAC and directly activating G‐coupled receptors (Koh et al., 2016), such as GPR41 and GPR43 (Barrows et al., 2015; Kobayashi et al., 2017).…”

Intestinal Microbiota - An Unmissable Bridge to Severe Acute Pancreatitis-Associated Acute Lung Injury

“…argued that picroside II increases the abundance of Lactobacillus , Prevotella , and restores the intestinal barrier by inhibiting the TLR4-dependent PI3K/AKT/NF-κB pathway, which thereby alleviates SAP ( 11 ) ( 176 ). Moreover, emodin has been reported to repair intestinal barrier functions and alleviate PALI by upregulating SCFA-producing bacteria (such as Akkermansia Muciniphila and Bacteroides ) ( 177 ).…”

The modulation of gut microbiota by herbal medicine to alleviate diabetic kidney disease – A review

“…It may be related to the increase in the abundance of commensal organisms and the decrease in the abundance of conditionally pathogenic species. Another study by the same research team found that Rheum palmatum L. enema (0.2 g/ml×5 ml) increased the content of SCFAs in the intestine of 5/6 Nephrectomy rats by increasing the abundance of SCFA-producing flora such as Akkermansia-muciniphila , lactobacillus-acidophilus , Bacteroides-caccae , and Faecalibaculum-rodentium , thereby regulating tight junction proteins and repairing the damaged intestinal barrier, which reduced inflammation and improved kidney functions ( Ji et al, 2022 ). In the three studies described above, Rheum palmatum L. granules were used.…”