The Probiotic Parabacteroides johnsonii Ameliorates Metabolic Disorders Through Promoting BCAAs to BSCFAs Conversion

The gut bacterium Parabacteroides spp. is increasingly recognized for its therapeutic potential in treating metabolic disorders. However, the role of Parabacteroides johnsonii in metabolic disorders is never reported. Here, this study finds that the abundance of P. johnsonii in the feces is 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 is correlated to the symptoms of obese patients. Isobutyrate intervention mirrored the favorable 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 exerted anti-obesity effects by enhancing the growth of P. johnsonii. These results offered insights into the mechanisms underlying the potential of P. johnsonii, isobutyrate, and stachyose in treating metabolic disorders.