Leptin receptor gene influences pig gut microbiota both through feed intake and independently

Adiposity results from a complex interplay among host genetics, diet and gut microbiota. Major genes are valuable models for unravelling how host genetics influence microbiota. The defective recessive T allele of the rs709596309 (C > T) polymorphism in the porcine leptin receptor gene (LEPR) leads to hyperphagia and obesity. Here, we report the first results on the impact of LEPR on microbiota composition in pigs. To this end, we compared saliva and faecal microbiota of 46 TT and 48 C− (22 CC and 26 CT) Duroc pigs from the same line and correlated the observed microbial changes with feed intake, faecal volatile fatty acid composition and lean growth. The TT genotype induced a shift in the faecal but not the saliva microbiota, accompanied by a substitution of faecal isovaleric acid for butyric acid. Fourteen genera were identified as microbial candidates influenced by LEPR in the gut. Of these, six genera were prevalent across all pigs, including three Oscillospiraceae genera (UCG-005, NK4A214, and UGC-002) and Treponema, which were less abundant in TT pigs, as well as Subdoligranulum and Coprococcus, which were more abundant. Oscillospiraceae UCG-005 experienced the greatest decrease with the TT genotype (-3.20%), while Subdoligranulum (+ 1.60%) showed the greatest increase. The most abundant genera in TT pigs were positively correlated with butyric acid and negatively correlated with isovaleric acid, and vice versa. The association of these LEPR-associated genera with body weight and fatness aligned with their relationship to faecal butyric and isovaleric acids. Variation in feed intake strongly explained their abundance, such that after accounting for feed intake, LEPR was associated only with Oscillospiraceae UCG-005 and four occasional bacteria (Frisingicoccus, Lachnospiraceae UCG-009, Lachnospiraceae XPB1014 and Megasphera). These occasional genera were found in 56.4% to 77.7% of the pigs, with only Megasphera exhibiting higher abundance in TT pigs. Disfunction of LEPR led to a shift in the gut microbiota, favouring the enrichment of starch-degrading rather than protein-degrading genera. Our results underscore the importance of feed intake as a microbiota-altering factor, as well as the potential of Oscillospiraceae UCG-005 as a LEPR-specific microbial biomarker associated with obesity.