Abnormal adipose tissue-derived microbes drive metabolic disorder and exacerbate postnatal growth retardation in piglet

Postnatal growth retardation(PGR)frequently occurs during early postnatal development of piglets and induces high mortality.To date,the mechanism of PGR remains poorly understood.Adipose tissue-derived microbes have been documented to be associated with several disorders of metabolism and body growth.However,the connection between microbial disturbance of adipose tissue and pig PGR remains unclear.Here,we investigated piglets with PGR and found that the adipose tissue of PGR piglets was charac-terized by metabolism impairment,adipose abnormality,and specific enrichment of culturable bacteria from Proteobacteria.Gavage of Sphingomonas paucimobilis,a species of Sphingomonas genus from the alphaproteobacteria,induced PGR in piglets.Moreover,this bacterium could also lead to metabolic disorders and susceptibility to acute stress,resulting in weight loss in mice.Mechanistically,multi-omics analysis indicated the changes in lipid metabolism as a response of adipose tissue to abnormal microbial composition.Further experimental tests proved that one of the altered lipids phosphatidylethanolamines could rescue the metabolism disorder and growth retardation,thereby suppressing the amount of Sphingomonas in the adipose tissue.Together,these results highlight that the microbe–host crosstalk may regulate the metabolic function of adipose tissue in response to PGR.