Alleviating chronic kidney disease progression through modulating the critical genus of gut microbiota in a cisplatin-induced Lanyu pig model

Highlights

• This is the first trial to use a minipig model to evaluate the probiotics on preventing cisplatin-induced renal dysfunction.

• The preventing effect of Probiotic mix 1 (Pm1) was associated with the reduction of inflammation, apoptosis, and oxidation.

• The reduction of the symptoms of chronic kidney disease (CKD) was regulated by manipulating microbiota via Pm1 intervention.

• This study underscored the importance of the tripartite relationship among the host, microbiota, and metabolites in CKD.

Abstract

In the present study, we investigated the effects of Probiotic mix 1 (Pm1) with Lactobacillus plantarum subsp. plantarum, Lactobacillus paracasei subsp. paracasei, and Streptococcus salivarius subsp. thermophilus on preventing renal injury using a chronic kidney disease (CKD) minipig model previously developed in our lab using cisplatin-induced CKD in Lanyu pigs. The results indicated that the high dosage Pm1 (H.Pm1) group demonstrated lower incidence of lesions, including atrophy, mononuclear inflammation, cell infiltration, and interstitial fibrosis in renal tubules in hematoxylin and eosin (H&E) and Masson’s trichrome stain. We further systematically investigated the preventing effect of Pm1. The H.Pm1 group decreased inflammatory cytokines production and increased the level of superoxide dismutase activity in plasma. The pigs fed with high dosage of Pm1 group also showed reduced both creatinine and blood urea nitrogen (BUN) when compared with the cisplatin group. Microbiota results indicated that Pm1-intervention not only reduced the abundance of Gram-negative bacteria but also affected the abundance of specific genera biomarkers, Anaerovibrio, possible_genus_SK018, Holdemanella, and Lachnospiraceae_UCG_010 in gut microbiota, leading to decreased inflammation and apoptosis in the kidney and further prevention/alleviation of the symptoms of CKD.