Inactivation of the MSTN gene expression changes the composition and function of the gut microbiome in sheep

Abstract

Background Myostatin (MSTN) negatively regulates the muscle growth in animals and MSTN deficient sheep have been widely reported previously. The goal of this study was to explore how MSTN inactivation influences their gut microbiota composition and potential functions. Results We compared the slaughter parameters and meat quality of 3 MSTN-edited male sheep and 3 wild-type male sheep, and analyzed the gut microbiome of the MSTN-edited sheep (8 female and 8 male sheep) and wild-type sheep (8 female and 8 male sheep) through metagenomic sequencing. The results showed that the body weight, carcass weight and eye muscle area of MSTN-edited sheep were significantly higher, but there were no significant differences in the meat quality indexes. At the microbial level, the alpha diversity was significantly higher in the MSTN-edited sheep (P < 0.05), and the microbial composition was significantly different by PCoA analysis in the MSTN-edited and wild-type sheep. The abundance of Firmicutes significantly increased and Bacteroidota significantly decreased in the MSTN-edited sheep. At genus level, the abundance of Flavonifractor, Subdoligranulum, Ruthenibacterium, Agathobaculum, Anaerotignum, Oribacterium and Lactobacillus were significantly increased in the MSTN-edited sheep (P < 0.05). Further analysis of functional differences was found that the carotenoid biosynthesis was significantly increased and the peroxisome, apoptosis, ferroptosis, N-glycan biosynthesis, thermogenesis, and adipocytokines pathways were decreased in the MSTN-edited sheep (P < 0.05). Moreover, carbohydrate-active enzymes (CAZymes) results certified the abundance of the GH13_39, GH4, GH137, GH71 and PL17 were upregulated, and the GT41 and CBM20 were downregulated in the MSTN-edited sheep (P < 0.05). Conclusions Our study suggested that MSTN inactivation remarkably influenced the composition and potential function of hindgut microbial communities of the sheep, and significantly promoted growth performance without affecting meat quality.

When Less Is More: Targeting the Myostatin Gene in Livestock for Augmenting Meat Production

“…Moreover, main meat quality characteristics, including pH, drip loss, intramuscular fat, crude protein, and shearing force of gluteal muscles, did not show changes between the MSTN -edited and WT lambs . A more recent investigation showed that the body weight, carcass weight, and eye muscle area of MSTN -edited sheep were significantly higher than those of WT sheep, with no significant differences in the meat quality indexes . Additionally, targeting the MSTN gene could induce changes in the composition and function of the gut microbiome between the MSTN -edited and WT sheep …”

“…114 Additionally, targeting the MSTN gene could induce changes in the composition and function of the gut microbiome between the MSTN-edited and WT sheep. 114 The MSTN multiplex edited sheep were also utilized to assess potential off-target activities and to comprehensively analyze the sequence data for de novo single nucleotide variants (SNVs), small insertions and deletions (Indels), and structural variations (SVs) at the genomic level. 115 The trio-based sequencing approach revealed a low incidence of SNVs and Indels and almost negligible off-target modifications.…”

“…A more recent investigation showed that the body weight, carcass weight, and eye muscle area of MSTN -edited sheep were significantly higher than those of WT sheep, with no significant differences in the meat quality indexes . Additionally, targeting the MSTN gene could induce changes in the composition and function of the gut microbiome between the MSTN -edited and WT sheep …”

“…113 A more recent investigation showed that the body weight, carcass weight, and eye muscle area of MSTN-edited sheep were significantly higher than those of WT sheep, with no significant differences in the meat quality indexes. 114 Additionally, targeting the MSTN gene could induce changes in the composition and function of the gut microbiome between the MSTN-edited and WT sheep. 114 The MSTN multiplex edited sheep were also utilized to assess potential off-target activities and to comprehensively analyze the sequence data for de novo single nucleotide variants (SNVs), small insertions and deletions (Indels), and structural variations (SVs) at the genomic level.…”

— Invited Review — Translational gut microbiome research for strategies to improve beef cattle production sustainability and meat quality

“…In addition, cattle with myostatin gene mutation which negatively regulates muscle development was shown to affect the metabolism of Ruminococcaceae_UCG-013 , Clostridium_sensu_stricto_1 and Ruminococcaceae_UCG-010 in the gut [ 40 ]. Myostatin-edited sheep increased abundance of Firmicutes , whereas decreased abundance of Bacteroidota [ 41 ], suggesting that muscle development and gut microbiota are closely involved.…”