Thiol-producing microbiota of the intestine modulate oxidative stress and inflammation in Chronic Kidney Disease

Background: Inflammation and oxidative stress are among the key contributing risk factors for cardiovascular disease (CVD) in chronic kidney disease (CKD). The human gut is the home for microbiota, of which some of the gram-negative gut bacteria are known to produce low-molecular-weight thiols including glutathione (GSH). GSH is used by mammals and eukaryotic cells as a substrate of glutathione peroxidase to eliminate reactive oxygen species. This study aims to investigate whether the presence of thiol-producing gut microbiota in CKD affects the level of oxidative stress and inflammation markers. Methods: This study examined the stool sample of 41 CKD patients at three hospitals in Surabaya, Indonesia to identify the gram-negative bacteria producing thiols. Based on Ellman's assay result, the study participants were grouped into patients with thiol-producing and non-thiol-producing gram-negative gut microbiota. The markers of inflammation, high sensitivity C-reactive protein (hs-CRP), total antioxidant capacity (TAC), and urinary oxidative stress marker 8-hydroxy-2'-deoxyguanosine (8-OHdG) were compared between the two groups. Results: The group with thiol-producing gut microbiota exhibited lower levels of plasma hs-CRP and urinary 8- OHdG compared to the group with non-thiol-producing gram-negative gut microbiota. In contrast, the group with thiol-producing gut microbiota has higher TAC compared to the group with non-thiol- producing gram-negative gut microbiota. Conclusion: This study emphasized that the phenotypical diversity regarding the ability to produce low-molecular-weight thiols might modulate inflammation and oxidative stress as CVD risk factors in CKD.