Integrative metagenomic profiling identifies unique gut microbial signatures linked to moderate to severe acne

The microbiota plays a crucial role in the pathogenesis of acne vulgaris. While the skin microbiome has been implicated in acne development, emerging research on the gut-skin axis suggests that the gut microbiota also contributes to acne. However, the alterations in species composition and function of the gut microbiome in moderate to severe acne remain insufficiently understood. In this study, we employed a multi-omics approach, integrating metagenomics and metabolomics, to investigate the gut microbiota and metabolites with the aim of elucidating the changes in gut microbiota composition and its profound role in disease pathogenesis. Metagenomic analysis was used to explore the characteristics of gut microbiota in the moderate to severe acne group and the healthy control group. We identified significant alterations in the gut microbiota between the two groups, including 20 species, such as Sutterella wadsworthensis , Clostridium sp. CAG:7, Sutterella parvirubra , Alistipes finegoldii, Alistipes onderdonkii, Eubacterium ventriosum, Eubacterium sp. CAG:274, Collinsella aerofaciens, Bacteroides sp. 1_1_6 , Bacteroides clarus, Bacteroides sp. D22, etc., which may contribute to the inflammation of acne. The KEGG functional enrichment and pathway analysis of gut microbiota revealed that acne microbiota may be related to methionyl-tRNA synthetase, tyrosyl-tRNA synthetase, ethanolamine ammonia-lyase large subunit, malonate-semialdehyde dehydrogenase (acetylating)/methylmalonate-semialdehyde dehydrogenase, and participate in the aminoacyl tRNA biosynthesis, glycerophospholipid metabolism pathway, β-alanine metabolism pathway. To understand the interaction between gut microbes and the host, we also examined the fecal metabolome and conducted a correlation analysis with fecal microorganisms. The specific-unique fecal metabolites in acne group were mainly concentrated in glycerolipid metabolism and linoleic acid metabolism, and many microorganisms were positively correlated with Cer (ceramide) (d18:1/16:0), Cer (d18:1/18:1), nicotinic acid, 3-methylxanthine, negatively correlated with 2-hydroxyisocaproic acid. Bacteroides sp. 1_1_6 was positively correlated with a variety of metabolites. Our study suggested that changes in gut microbes of moderate and severe acne may play a role in the inflammatory response of acne. In addition, the gut microbiome of acne patients may affect host function by regulating glycerolipid metabolism and linoleic acid metabolism. Our findings complement the species changes in the gut microbiome and metabolome of acne patients and provide an in-depth analysis of their impact on the host over the course of the disease.