Core-predominant gut fungus Kazachstania slooffiae promotes intestinal epithelial glycolysis via lysine desuccinylation in pigs

Background Gut fungi are increasingly recognized as important contributors to host physiology, although most studies have focused on gut bacteria. Post-translational modifications (PTMs) of proteins play vital roles in cell metabolism. However, the contribution of gut fungi to host protein PTMs remains unclear. Mining gut fungi that mediate host protein PTMs and dissecting their mechanism are urgently needed. Results We studied the gut fungal communities of 56 weaned piglets and 56 finishing pigs from seven pig breeds using internal transcribed spacer (ITS) gene amplicon sequencing and metagenomics. The results showed that Kazachstania slooffiae was the most abundant gut fungal species in the seven breeds of weaned piglets. K. slooffiae decreased intestinal epithelial lysine succinylation levels, and these proteins were especially enriched in the glycolysis pathway. We demonstrated that K. slooffiae promoted intestinal epithelial glycolysis by decreasing lysine succinylation by activating sirtuin 5 (SIRT5). Furthermore, K. slooffiae -derived 5′-methylthioadenosine metabolite promoted the SIRT5 activity. Conclusions These findings provide a landscape of gut fungal communities of pigs and suggest that K. slooffiae plays a crucial role in intestinal glycolysis metabolism through lysine desuccinylation. Our data also suggest a potential protective strategy for pigs with an insufficient intestinal energy supply. 6wx82pHd_v1w2-kqvetnhK Video Abstract