Adiposity and inflammation mediate altered metabolic profile in individuals with opioid use disorder.

Depression is a common mental disorder, which causes individuals to suffer from long-term depressed mood, slow thinking and other symptoms, and has a wide range of effects on the physical, cognitive, emotional and social processes of patients []. An increasing body of evidence suggests that depression commonly co-occurs with autoimmune diseases (ADs), which involve aberrant immune responses targeting host tissues [–]. ADs comprise a heterogeneous group of chronic immune-mediated conditions, including rheumatoid arthritis, systemic lupus erythematosus, multiple sclerosis, psoriasis, and inflammatory bowel disease (IBD). Among these, IBD is characterized by persistent inflammation of the gastrointestinal tract and has been consistently associated with alterations in gut microbial composition and function, making it particularly relevant for investigations of microbiome-related comorbidities []. Many epidemiological studies have found a high prevalence of comorbid depression in patients with different types of ADs, which can exacerbate disease severity, complicate treatment, and reduce quality of life [, ]. The gut microbiome has emerged as a potential factor linking depression and ADs through the gut-brain-immune axis []. Microbial dysbiosis has been associated with both inflammatory processes in ADs and neurobehavioral alterations seen in depression [–]. For instance, increased abundances of and have been found linked to the inflammatory response, whereas reduced has been associated with mood-regulated amino acid synthesis and modulation of host autoimmunity via bile acid pathways [, –]. This evidence suggests the important roles of gut microbes in the comorbidity of AD and depression. While mechanistic studies have provided insights into potential microbiota-mediated pathways in AD-depression comorbidity [, ], large-scale, population-based microbiome analyses remain limited, particularly for the broader spectrum of ADs beyond IBD. Given the distinct gastrointestinal involvement in IBD and its high depression comorbidity, we also aimed to explore whether IBD might present unique or shared microbial signatures compared to other ADs []. In this study, we analyzed two gut microbiome cohorts derived from the American Gut Project (AGP). The overall study population comprised individuals with ADs, with and without comorbid depression, as well as healthy controls. Within the AD cohort, an IBD subgroup was defined and analyzed separately to enable subgroup-specific comparisons. We have examined patterns of gut microbiota alterations across groups. We also predicted the functional pathways of differentially abundant microorganisms between groups, which may help identify potential biomarkers and provide new clues and methods for the diagnosis and treatment of comorbid AD and depression. By clarifying the intestinal microbial characteristics of patients with AD and depression comorbidities, it provides microbiological evidence for the pathophysiological mechanisms of the two comorbidities and facilitates the identification or discovery of biomarkers that can be used for the prediction, diagnosis, and treatment of the comorbidities-related biomarkers.