Obesity and its comorbidities are currently considered an epidemic, and the involved pathophysiology is well studied. Hypercaloric diets are tightly related to the obesity etiology and also cause alterations in gut microbiota functionality. Diet and antibiotics are known to play crucial roles in changes in the microbiota ecosystem and the disruption of its balance; therefore, the manipulation of gut microbiota may represent an accurate strategy to understand its relationship with obesity caused by diet. Fecal microbiota transplantation, during which fecal microbiota from a healthy donor is transplanted to an obese subject, has aroused interest as an effective approach for the treatment of obesity. To determine its success, a multiomics approach was used that combined metagenomics and metaproteomics to study microbiota composition and function. To do this, a study was performed in rats that evaluated the effect of a hypercaloric diet on the gut microbiota, and this was combined with antibiotic treatment to deplete the microbiota before fecal microbiota transplantation to verify its effects on gut microbiota-host homeostasis. Our results showed that a high-fat diet induces changes in microbiota biodiversity and alters its function in the host. Moreover, we found that antibiotics depleted the microbiota enough to reduce its bacterial content. Finally, we assessed the use of fecal microbiota transplantation as a complementary obesity therapy, and we found that it reversed the effects of antibiotics and reestablished the microbiota balance, which restored normal functioning and alleviated microbiota disruption. This new approach could be implemented to support the dietary and healthy habits recommended as a first option to maintain the homeostasis of the microbiota.

Clinical conditions commonly associated with mitochondrial disorders (CAMDs) are often present in autism spectrum disorders (ASD) and intellectual disability (ID). Therefore, the mitochondrial dysfunction hypothesis has been proposed as a transversal mechanism that may function in both disorders. Here, we investigated the presence of conditions associated with mitochondrial disorders and mitochondrial DNA (mtDNA) alterations in 122 subjects who presented ASD with ID (ASD group), 115 subjects who presented ID but not ASD (ID group) and 112 healthy controls (HC group). We assessed in the three study groups the presence of the clinical conditions through a questionnaire and the mtDNA content of two mitochondrial genes, MT-ND1 and MT-ND4, by qPCR. The mtDNA sequences of 98 ASD and 95 ID subjects were obtained by mtDNA-targeted next generation sequencing and analysed through the MToolBox pipeline to identify mtDNA mutations. Subjects with ASD and ID showed higher frequencies of constipation, edema, seizures, vision alterations, strabismus and sphincter incontinence than HCs subjects. ASD and ID subjects showed significantly lower mtDNA content than HCs in both MT-ND1 and MT-ND4 genes. In addition, we identified 49 putative pathogenic variants with a heteroplasmy level higher than 60%: 8 missense, 29 rRNA and 12 tRNA variants. A total of 28.6% of ASD and 30.5% of ID subjects carried at least one putative pathogenic mtDNA mutation. The high frequency of CAMDs, the low mtDNA content and the presence of putative pathogenic mtDNA mutations observed in both ASD and ID subjects are evidence of mitochondrial dysfunction in ASD and ID.