Organ Correlation and Antiaging Medicine: Intestinal-Kidney Correlation and Antiaging

Nutrients ingested by humans are metabolized by intestinal bacteria into short-chain fatty acids with anti-inflammatory and metabolic regulatory effects, antioxidants, amino acids, vitamins, etc., which are involved in maintaining human health. In symbiosis where beneficial resident bacteria coexist, intestinal bacteria break down dietary fiber to produce short-chain fatty acids such as propionic acid, butyric acid, and acetic acid. These short-chain fatty acids serve as nutrients for the intestinal epithelium, maintaining the intestinal barrier function, inducing regulatory T cells (Treg) that suppress inflammation, promoting the secretion of GLP-1, an intestinal hormone with a blood sugar lowering effect, and controlling glucose metabolism and lipid metabolism, thus having a preventive effect on diabetes and hypertension [1] (Fig. 55.1a). Also, the intestine forms an intestinal barrier composed of intestinal epithelial cells, the intestinal mucus layer, antimicrobial peptides secreted from intestinal epithelial cells, and secretory dimeric IgA secreted from IgA-producing plasma cells under the mucosa, preventing the invasion of pathogenic bacteria and bacterial lipopolysaccharides (LPS) into the body [1] (Fig. 55.1a). On the other hand, indoxyl sulfate, p-cresyl sulfate, and phenyl sulfate, which are uremic toxins accumulated in the body of patients with chronic kidney disease (CKD), are intestinal-derived uremic toxins produced by the metabolism of tryptophan and tyrosine, amino acids derived from dietary protein, by intestinal bacteria into precursor substances such as indole, p-cresol, and phenol, which are then sulfated in the liver [1, 2] (Fig. 55.1b). In CKD patients, dysbiosis, a state of deterioration of the intestinal bacterial environment due to changes in the intestinal microbiota caused by constipation, dietary fiber intake restriction, frequent use of antibiotics, impairment of the intestinal barrier, and uremic toxins, exists [3]. In the intestinal microbiota of CKD patients, the number of beneficial bacteria such as Bifidobacterium, Lactobacillus, and Roseburia spp., which produce butyric acid, decreases, while the number of bacteria involved in the production of uremic toxins such as indoxyl sulfate and p-cresyl sulfate increases [3]. In addition, in CKD, intestinal bacteria and LPS penetrate the intestinal barrier due to impairment of the intestinal barrier, infiltrating the submucosal tissue of the intestine and the bloodstream, inducing T helper 17 cells (Th17). This further activates macrophages and induces Tumor Necrosis Factor-alpha (TNF-α), Interleukin-6 (IL-6), Interleukin-1 (IL-1), and other inflammatory cytokines’ increase, causing oxidative stress and chronic inflammation throughout the body, leading to the progression of arteriosclerosis, hypertension, diabetes, sarcopenia, and other aging-related diseases, thereby further exacerbating Chronic Kidney Disease (CKD) itself, creating a “vicious cycle” (Fig. 55.1b).