Obesity is an excessive fat accumulation that could lead to complications like metabolic syndrome. There are reports on gut microbiota and metabolic syndrome in relation to dietary, host genetics, and other environmental factors; however, it is necessary to explore the role of the gut microbiota metabolic pathways in populations like Mexicans, where the prevalence of obesity and metabolic syndrome is high. This study identify alterations of the gut microbiota in a sample of healthy Mexican women (CO), women with obesity (OB), and women with obesity plus metabolic syndrome (OMS). We studied 67 women, characterizing their anthropometric and biochemical parameters along with their gut bacterial diversity by high-throughput DNA sequencing. Our results indicate that in OB or OMS women, Firmicutes was the most abundant bacterial phylum. We observed significant changes in abundances of bacteria belonging to the Ruminococcaceae, Lachnospiraceae, and Erysipelotrichaceae families and significant enrichment of gut bacteria from 16 different taxa that might explain the observed metabolic alterations between the groups. Finally, the predicted functional metagenome of the gut microbiota found in each category shows differences in metabolic pathways related to lipid metabolism. We demonstrate that Mexican women have a particular bacterial gut microbiota characteristic of each phenotype. There are bacteria that potentially explain the observed metabolic differences between the groups, and gut bacteria in OMS and OB conditions carry more genes of metabolic pathways implicated in lipid metabolism.

Obesity is a metabolic disease characterized by low-grade inflammation and accompanied by dyslipidemia and up-regulation of other bioactive molecules, creating a predisposition to endothelial dysfunction and metabolic syndrome. We studied the association between gut microbiota diversity and endothelial dysfunction (EDF) markers in obese Mexican children and adolescents. We examined clinical data including metabolic factors and EDF markers in blood samples. Gut bacterial diversity was characterized by high-throughput sequencing of V3-16S rDNA libraries. Triglycerides, insulin, homeostasis model assessment-insulin resistant (HOMA-IR), leptin, C-reactive protein (CRP), and EDF marker intercellular adhesion molecule 1 (ICAM-1) were significantly higher in obese children and adolescents. Multivariate analysis showed statistically significant positive associations between vascular cell adhesion molecule 1 (VCAM-1) and Veillonellaceae, and between ICAM-1 and Ruminococcus in obese children. In obese adolescents, there was a statistically significant positive association between total cholesterol and Ruminococcus, and between ICAM-1 and Bacteroides. LEfSe analysis showed that the genus Lactobacillus and family Coriobacteriaceae were enriched in children, and genera Collinsella and Prevotella were enriched in obese adolescents. Obese children and adolescents had higher levels of insulin resistance and metabolic syndrome. These results suggest that obese Mexican children and adolescents had increased levels of CRP and a reduction of adiponectin, which causes higher expression of EDF markers, affecting endothelial function and associating with changes in the gut microbiota.

Links between gut microbiota and autism spectrum disorder (ASD) have been explored in many studies using 16S rRNA gene amplicon and shotgun sequencing. Based on these links, microbiome therapies have been proposed to improve gastrointestinal (GI) and ASD symptoms in ASD individuals. Previously, our open-label microbiota transfer therapy (MTT) study provided insight into the changes in the gut microbial community of children with ASD after MTT and showed significant and long-term improvement in ASD and GI symptoms. Using samples from the same study, the objective of this work was to perform a deeper taxonomic and functional analysis applying shotgun metagenomic sequencing. Taxonomic analyses revealed that ASD Baseline had many bacteria at lower relative abundances, and their abundance increased after MTT. The relative abundance of fiber consuming and beneficial microbes including Prevotella (P. dentalis, P. enoeca, P. oris, P. meloninogenica), Bifidobacterium bifidum, and a sulfur reducer Desulfovibrio piger increased after MTT-10wks in children with ASD compared to Baseline (consistent at genus level with the previous 16S rRNA gene study). Metabolic pathway analysis at Baseline compared to typically developing (TD) children found an altered abundance of many functional genes but, after MTT, they became similar to TD or donors. Important functional genes that changed included: genes encoding enzymes involved in folate biosynthesis, sulfur metabolism and oxidative stress. These results show that MTT treatment not only changed the relative abundance of important genes involved in metabolic pathways, but also seemed to bring them to a similar level to the TD controls. However, at a two-year follow-up, the microbiota and microbial genes shifted into a new state, distinct from their levels at Baseline and distinct from the TD group. Our current findings suggest that microbes from MTT lead to initial improvement in the metabolic profile of children with ASD, and major additional changes at two years post-treatment. In the future, larger cohort studies, mechanistic in vitro experiments and metatranscriptomics studies are recommended to better understand the role of these specific microbes, functional gene expression, and metabolites relevant to ASD.

Para-cresol (p-cresol), and its primary human metabolite p-cresol sulfate (pCS), are among the most studied gut-derived metabolites relevant to autism spectrum disorder (ASD). P-cresol is produced by bacterial modification of phenylalanine or tyrosine and is one of many potentially deleterious metabolites produced by the gut microbiota. Seventeen studies have observed p-cresol and/or p-cresol sulfate as being higher in the urine of children with autism spectrum disorder (ASD) vs. controls. P-cresol has harmful effects on the body, including within the gut, brain, kidneys, liver, immune system, and mitochondria. Some of these effects may contribute to autism and comorbid symptoms. In the gut, p-cresol acts as an antibiotic, altering the gut microbiome to favor the bacteria that produce it. In the mitochondria, p-cresol disrupts ATP production and increases oxidative stress, which is also common in autism. In the brain, p-cresol impairs neuronal development. P-cresol inactivates dopamine beta-hydroxylase, which converts dopamine to noradrenaline. P-cresol sulfate impairs kidney function and is linked to chronic kidney disease (CKD), which is more common in ASD adults. P-cresol also interferes with immune function. Three animal studies have demonstrated that p-cresol causes autism-related symptoms in mice, and that mice can be recovered by the administration of fecal microbiota transplant from healthy mice. Similarly, it was found that microbiota transplant therapy treatment in children with ASD significantly reduced p-cresol sulfate levels to normal and led to significant improvements in gastrointestinal (GI) and ASD symptoms. In summary, p-cresol and pCS likely contribute to ASD core symptoms in a substantial subset of children with ASD.