Effect of nutritionally complete formula on gut microbiota and their metabolite in fecal batch fermentation system

Background: Emerging evidence has revealed that the gut microbiota is significantly altered, contributing to the occurrence and development of chronic kidney disease (CKD). Therefore, the target of increasing short-chain fatty acids (SCFAs) and lactic acid production and reduction of uremic toxins were interested. Objective: To study the effect of the nutritionally complete formula (Synplus) developed for hemodialysis patients on gut microbiota and their metabolite in in vitro fecal fermentation of healthy volunteers.Methods: Fecal fermentation (in vitro) using batch culture in an environment mimicking human large intestine was used to study the change of gut microbiota by next generation sequencing (NGS) during fermentation of the developed formula (Synplus), commercial formula (Nepro®) and control. The gut metabolites were determined including short-chain fatty acids (acetic, propionic, and butyric) and lactic acid. The uremic toxins (p-cresol and indole) were determined by high performance liquid chromatography (HPLC).Results: The increase of Lactobacillus spp. (53.74%) and Bifidobacterium spp. (29.35%) was observed in the developed product (Synplus) compared with control at 48 hrs fermentation meanwhile, these genera were decreased in a commercial product (Nepro®). Moreover, the abundance of the genus Escherichia spp. (12.33%) was observed in Nepro® fermentation, with Escherichia albertii species which is a newly discovered pathogen of the gastrointestinal tract. Microbial metabolites produced by fecal fermentation of Synplus revealed that propionate, acetate, and butyrate increased significantly (p<0.05). All the samples evaluated exhibited acetate in abundance when compared to other SCFAs. Acetate was the most abundant SCFA in all samples. The concentrations of acetate for Synplus fermentation were 15.63±3.26, 147.29±2.39, 162.28±4.13 and 189.39±0.17 mM at 0, 12, 24, and 48 hrs respectively. Total SCFAs produced from Synplus was significantly increased (p<0.05) and higher than control and Nepro®, respectively. The concentration of p-cresol at 48 hrs fermentation for control, Synplus and Nepro® were 3.79±0.12, 6.31±2.37 and 11.59±0.10 µg/mL, respectively. The indole concentration of control, Synplus and Nepro® were 3.64±0.08, 15.06±3.56 and 12.81±1.68 µg/mL, respectively. There were also indicated that imbalance of gut microbiota was related with the ratio of uremic toxins (indole and p-cresol) to SCFAs.CONCLUSION: The synbiotic product containing prebiotic and probiotic may be used to improve gut microbiota thus reducing the risk of kidney disease.Keywords: synbiotic, gut microbiota, uremic toxins, SCFA, CKD