The probiotic Parabacteroides johnsonii ameliorates metabolic disorders through promoting BCAAs to BSCFAs conversion

The gut bacterium Parabacteroides spp. has been increasingly recognized for its therapeutic potential in treating metabolic disorders. However, the role of Parabacteroides johnsonii in metabolic disorders has never been reported. Here, we found that the abundance of P. johnsonii in the feces was negatively correlated with the blood glucose and lipid levels of obese patients. Oral administration of live P. johnsonii improved the metabolic dysfunction in high fat diet (HFD)-fed mice, accompanied by the alleviation of leaky gut and the systemic inflammation. P. johnsonii enhanced the catabolism of branched-chain amino acids (BCAAs) to branched-chain short-chain fatty acids (BSCFAs) in gut. Particularly, the conversion of valine to isobutyrate was correlated to the symptoms of obese patients. Isobutyrate intervention mirrored the favourable effects of P. johnsonii on HFD-fed mice. Isobutyrate increased H3K14 acetylation at Fgf1b promoters and activated its transcription through inhibition of HDAC3 in colon, thereby maintaining the intestinal barrier integrity. The natural product stachyose exhibited its anti-obesity effects by promoting the growth of P. johnsonii. Our findings provided mechanistic insights into the therapeutic potential of P. johnsonii, isobutyrate and stachyose in treating metabolic disorders. Overall design: RNA-seq profiling of colon from HFD fed C57BL/6J mouse and HFD fed treating with isobutyrate mouse