Role of Presurgical Gut Microbial Diversity in Roux-en-Y Gastric Bypass Weight-Loss Response: A Cohort Study.

INTRODUCTION: Roux-en-Y gastric bypass (RYGB) substantially alters the gut microbial composition which could be associated with the metabolic improvements seen after surgery. Few studies have been conducted in Latin American populations, such as Mexico, where obesity prevalence is above 30% in the adult population. Thus, the aim of this study was to characterize the changes in the gut microbiota structure in a Mexican cohort before and after RYGB and to explore whether surgery-related changes in the microbial community were associated with weight loss. METHODS: Biological samples from patients who underwent RYGB were examined before and 12 months after surgery. Fecal microbiota characterization was performed through 16S rRNA sequencing. RESULTS: Twenty patients who underwent RYGB showed a median excess weight loss of 66.8% 12 months after surgery. Surgery increased alpha diversity estimates (Chao, Shannon index, and observed operational taxonomic units, p < 0.05) and significantly altered gut microbiota composition. Abundance of four genera was significantly increased after surgery: Oscillospira, Veillonella, Streptococcus, and an unclassified genus from Enterobacteriaceae family (PFDR < 0.1). The change in Veillonella abundance was associated with lower excess weight loss (rho = -0.446, p = 0.063) and its abundance post-surgery with a greater BMI (rho = 0.732, p = 5.4 × 10-4). In subjects without type 2 diabetes, lower bacterial richness and diversity before surgery were associated with a greater Veillonella increase after surgery (p < 0.05), suggesting that a lower bacterial richness before surgery could favor the bloom of certain oral-derived bacteria that could negatively impact weight loss. CONCLUSION: Presurgical microbiota profile may favor certain bacterial changes associated with less successful results.

Beneficial Effects of Plant-Based Diets on Skin Health and Inflammatory Skin Diseases.

The human skin is a crucial organ that protects the organism from the outer environment. Skin integrity and health depend on both extrinsic and intrinsic factors. Intrinsic factors such as aging and genetic background contribute to weakened skin and disease susceptibility. Meanwhile, extrinsic factors including UV radiation, pollution, smoking, humidity, and poor diet also affect skin health and disease. On the other hand, healthy dietary patterns such as plant-based diets have gained popularity as a complementary therapy for skin health. A plant-based diet is defined as all diets based on plant foods, including an abundance of vegetables, fruits, beans, lentils, legumes, nuts, seeds, fungi, and whole grains, with limited or no animal products or processed foods. However, some authors also exclude or limit processed foods in the definition. Recent research has shown that these diets have beneficial effects on inflammatory skin diseases. This review explored the beneficial effects of plant-based diets on inflammatory skin diseases and plant-based functional foods on healthy skin. In conclusion, plant-based diets and plant-based functional foods may have beneficial effects on skin health through the gut microbiome.

A metagenomic study identifies a Prevotella copri enriched microbial profile associated with non-alcoholic steatohepatitis in subjects with obesity.

BACKGROUND AND AIM: Non-alcoholic fatty liver disease (NAFLD) is the most common cause of liver disease. Increasing evidence indicates that the gut microbiota can play an important role in the pathophysiology of NAFLD. Recently, several studies have tested the predictive value of gut microbiome profiles in NAFLD progression; however, comparisons of microbial signatures in NAFLD or non-alcoholic steatohepatitis (NASH) have produced discrepant results, possibly due to ethnic and environmental factors. Thus, we aimed to characterize the gut metagenome composition of patients with fatty liver disease. METHODS: Gut microbiome of 45 well-characterized patients with obesity and biopsy-proven NAFLD was evaluated using shot-gun sequencing: 11 non-alcoholic fatty liver controls (non-NAFL), 11 with fatty liver, and 23 with NASH. RESULTS: Our study showed that Parabacteroides distasonis and Alistipes putredenis were enriched in fatty liver but not in NASH patients. Notably, in a hierarchical clustering analysis, microbial profiles were differentially distributed among groups, and membership to a Prevotella copri dominant cluster was associated with a greater risk of developing NASH. Functional analyses showed that although no differences in LPS biosynthesis pathways were observed, Prevotella-dominant subjects had higher circulating levels of LPS and a lower abundance of pathways encoding butyrate production. CONCLUSIONS: Our findings suggest that a Prevotella copri dominant bacterial community is associated with a greater risk for NAFLD disease progression, probably linked to higher intestinal permeability and lower capacity for butyrate production.

Gut microbiota composition after a dietary and physical activity intervention: a pilot study in Mexican children with obesity.

BACKGROUND: Gut microbiota is a complex organized collection of microorganisms that confers multiple metabolic advantages to the host. The reduced diversity and proportion of specific gut microbial species have been associated with obesity and metabolic disorders. Multidimensional interventions, including modifications in dietary and physical activity habits, are associated with favorable changes in microbiota composition. This pilot study aimed to evaluate changes in the gut microbiota composition of Mexican children with obesity before and after a 6-week multidimensional intervention. METHODS: Blood and stool samples were collected, and anthropometric measurements were obtained from six children with obesity before and after the intervention. The intervention consisted of modeling a hypo energetic diet and giving nutritional and physical activation recommendations. DNA from stool samples was used to characterize gut microbial composition by sequencing the 16S rRNA gene. RESULTS: The decrease in waist circumference was associated with increased Odoribacter relative abundance. However, gut microbiota composition and diversity remained unchanged. CONCLUSIONS: Although no modifications in the body mass index, body fat, composition, or diversity of the gut microbiota were observed with the intervention, it was possible to associate the reduction in waist circumference with the presence of Odoribacter after a multidimensional intervention in Mexican children with obesity.

INTRODUCCIÓN: La microbiota intestinal es un conjunto de microorganismos organizados de forma compleja que confieren múltiples ventajas metabólicas al hospedero. La reducida diversidad y la proporción de ciertas especies sobre otras se ha asociado con obesidad y enfermedades metabólicas. Las intervenciones multidimensionales, que incluyen modificaciones en los hábitos alimentarios y de actividad física, se asocian con cambios favorables en la composición de la microbiota. El objetivo de este estudio piloto fue evaluar la composición de la microbiota intestinal de niños mexicanos con obesidad, antes y después de una intervención multidimensional de seis semanas de duración. MÉTODOS: Se tomaron muestras de sangre y de heces y se realizaron las mediciones antropométricas de seis niños con obesidad, antes y después de la intervención. La intervención consistió en modelar una dieta hipoenergética y dar recomendaciones nutricias y de actividad física. A partir del DNA de las muestras de heces se realizó la caracterización de la microbiota intestinal por secuenciación del gen 16S del RNAr. RESULTADOS: La disminución de la circunferencia de cintura se asoció con un aumento en la abundancia del género Odoribacter. Sin embargo, no se encontraron cambios en la composición de la microbiota intestinal. CONCLUSIONES: A pesar de que la intervención no modificó el índice de masa corporal, masa grasa, composición ni diversidad de la microbiota intestinal, sí se logró asociar la reducción de la circunferencia de cintura con la abundancia de Odoribacter en el presente estudio piloto en niños mexicanos con obesidad.

Gut microbiota composition after a dietary and physical activity intervention: a pilot study in Mexican children with obesity / Efecto de una intervención nutricia y de actividad física sobre la composición de la microbiota intestinal: un estudio piloto en niños mexicanos con obesidad

Abstract Background: Gut microbiota is a complex organized collection of microorganisms that confers multiple metabolic advantages to the host. The reduced diversity and proportion of specific gut microbial species have been associated with obesity and metabolic disorders. Multidimensional interventions, including modifications in dietary and physical activity habits, are associated with favorable changes in microbiota composition. This pilot study aimed to evaluate changes in the gut microbiota composition of Mexican children with obesity before and after a 6-week multidimensional intervention. Methods: Blood and stool samples were collected, and anthropometric measurements were obtained from six children with obesity before and after the intervention. The intervention consisted of modeling a hypo energetic diet and giving nutritional and physical activation recommendations. DNA from stool samples was used to characterize gut microbial composition by sequencing the 16S rRNA gene. Results: The decrease in waist circumference was associated with increased Odoribacter relative abundance. However, gut microbiota composition and diversity remained unchanged. Conclusions: Although no modifications in the body mass index, body fat, composition, or diversity of the gut microbiota were observed with the intervention, it was possible to associate the reduction in waist circumference with the presence of Odoribacter after a multidimensional intervention in Mexican children with obesity.

Resumen Introducción: La microbiota intestinal es un conjunto de microorganismos organizados de forma compleja que confieren múltiples ventajas metabólicas al hospedero. La reducida diversidad y la proporción de ciertas especies sobre otras se ha asociado con obesidad y enfermedades metabólicas. Las intervenciones multidimensionales, que incluyen modificaciones en los hábitos alimentarios y de actividad física, se asocian con cambios favorables en la composición de la microbiota. El objetivo de este estudio piloto fue evaluar la composición de la microbiota intestinal de niños mexicanos con obesidad, antes y después de una intervención multidimensional de seis semanas de duración. Métodos: Se tomaron muestras de sangre y de heces y se realizaron las mediciones antropométricas de seis niños con obesidad, antes y después de la intervención. La intervención consistió en modelar una dieta hipoenergética y dar recomendaciones nutricias y de actividad física. A partir del DNA de las muestras de heces se realizó la caracterización de la microbiota intestinal por secuenciación del gen 16S del RNAr. Resultados: La disminución de la circunferencia de cintura se asoció con un aumento en la abundancia del género Odoribacter. Sin embargo, no se encontraron cambios en la composición de la microbiota intestinal. Conclusiones: A pesar de que la intervención no modificó el índice de masa corporal, masa grasa, composición ni diversidad de la microbiota intestinal, sí se logró asociar la reducción de la circunferencia de cintura con la abundancia de Odoribacter en el presente estudio piloto en niños mexicanos con obesidad.

Association of Gut Microbiota with Atherogenic Dyslipidemia, and Its Impact on Serum Lipid Levels after Bariatric Surgery.

Gut microbiota has been suggested to modulate circulating lipids. However, the relationship between the gut microbiota and atherogenic dyslipidemia (AD), defined as the presence of both low HDL-C and hypertriglyceridemia, is not fully understood. Moreover, because obesity is among the main causes of secondary AD, it is important to analyze the effect of gut microbiota composition on lipid profiles after a weight loss intervention. We compared the microbial diversity and taxonomic composition in patients with AD (n = 41) and controls (n = 38) and sought correlations of genera abundance with serum lipid levels in 20 patients after weight loss induced by Roux-en-Y gastric bypass (RYGB) surgery. Gut microbiota composition was profiled using next-generation sequencing of 16S rRNA. Gut microbiota diversity was significantly lower in atherogenic dyslipidemia. Moreover, relative abundance of two genera with LDA score >3.5 (Megasphaera and LPS-producing Escherichia-Shigella), was significantly higher in AD subjects, while the abundance of four short chain fatty acids (SCFA) producing-genera (Christensenellaceae R-7, Ruminococcaceae UCG-014; Akkermansia and [Eubacterium] eligens group) was significantly higher in controls. Notably, [Eubacterium] eligens group abundance was also significantly associated with higher HDL-C levels in RYGB patients one year after surgery. Although dietary polyunsaturated fatty acid/saturated fatty acid (PUFA/SFA) ratio and PUFA intake were higher in controls than in AD subjects, of the four genera differentiated in cases and controls, only Akkermansia abundance showed a positive and significant correlation with PUFA/SFA ratio. Our results suggest that SCFA-producing bacteria promote a healthy lipid homeostasis, while the presence of LPS-producing bacteria such Escherichia-Shigella may contribute to the development of atherogenic dyslipidemia.

Genome-Wide Association Study Identifies a Functional SIDT2 Variant Associated With HDL-C (High-Density Lipoprotein Cholesterol) Levels and Premature Coronary Artery Disease.

Objective: Low HDL-C (high-density lipoprotein cholesterol) is the most frequent dyslipidemia in Mexicans, but few studies have examined the underlying genetic basis. Our purpose was to identify genetic variants associated with HDL-C levels and cardiovascular risk in the Mexican population. Approach and Results: A genome-wide association studies for HDL-C levels in 2335 Mexicans, identified four loci associated with genome-wide significance: CETP, ABCA1, LIPC, and SIDT2. The SIDT2 missense Val636Ile variant was associated with HDL-C levels and was replicated in 3 independent cohorts (P=5.9×10−18 in the conjoint analysis). The SIDT2/Val636Ile variant is more frequent in Native American and derived populations than in other ethnic groups. This variant was also associated with increased ApoA1 and glycerophospholipid serum levels, decreased LDL-C (low-density lipoprotein cholesterol) and ApoB levels, and a lower risk of premature CAD. Because SIDT2 was previously identified as a protein involved in sterol transport, we tested whether the SIDT2/Ile636 protein affected this function using an in vitro site-directed mutagenesis approach. The SIDT2/Ile636 protein showed increased uptake of the cholesterol analog dehydroergosterol, suggesting this variant affects function. Finally, liver transcriptome data from humans and the Hybrid Mouse Diversity Panel are consistent with the involvement of SIDT2 in lipid and lipoprotein metabolism. Conclusions: This is the first genome-wide association study for HDL-C levels seeking associations with coronary artery disease in the Mexican population. Our findings provide new insight into the genetic architecture of HDL-C and highlight SIDT2 as a new player in cholesterol and lipoprotein metabolism in humans.

Nopal feeding reduces adiposity, intestinal inflammation and shifts the cecal microbiota and metabolism in high-fat fed rats.

Nopal is a cactus plant widely consumed in Mexico that has been used in traditional medicine to aid in the treatment of type-2 diabetes. We previously showed that chronic consumption of dehydrated nopal ameliorated hepatic steatosis in obese (fa/fa) rats; however, description of the effects on other tissues is sparse. The aim of the present study was to investigate the effects of nopal cladode consumption on intestinal physiology, microbial community structure, adipose tissue, and serum biochemistry in diet-induced obese rats. Rats were fed either a normal fat (NF) diet or a HF diet containing 4% of dietary fiber from either nopal or cellulose for 6 weeks. Consumption of nopal counteracted HF-induced adiposity and adipocyte hypertrophy, and induced profound changes in intestinal physiology. Nopal consumption reduced biomarkers of intestinal inflammation (mRNA expression of IL-6) and oxidative stress (ROS), modfied gut microbiota composition, increasing microbial diversity and cecal fermentation (SCFA), and altered the serum metabolome. Interestingly, metabolomic analysis of dehydrated nopal revealed a high choline content, which appeared to generate high levels of serum betaine, that correlated negatively with hepatic triglyceride (TAG) levels. A parallel decrease in some of the taxa associated with the production of trimethylamine, suggest an increase in choline absorption and bioavailability with transformation to betaine. The latter may partially explain the previously observed effect of nopal on the development of hepatic steatosis. In conclusion, this study provides new evidence on the effects of nopal consumption on normal and HF-diet induced changes in the intestine, the liver and systemic metabolism.

Hepatic miR-33a/miR-144 and their target gene ABCA1 are associated with steatohepatitis in morbidly obese subjects.

BACKGROUND AND AIM: Abnormal cholesterol metabolism may contribute to the pathogenesis of non-alcoholic steatohepatitis (NASH) and fibrosis. miR-33 and miR-144 regulate adenosine triphosphate binding cassette transporter (ABCA1) and other target genes involved in cholesterol efflux, fatty acid oxidation and inflammation. We explored relationships between non-alcoholic fatty liver disease (NAFLD) and the hepatic expression of ABCA1/ABCG1, as well as other target genes regulated by miR-33 (carnitine O-octanoyltransferase, CROT and hydroxyacyl-CoA-dehydrogenase ß-subunit, HADHB) and miR-144 (toll-like receptor-2, TLR2). Moreover, we evaluated whether the expression of these genes is correlated with miR-33a/b and miR-144 expression in Mexican individuals with morbid obesity. METHODS: Eighty-four morbidly obese subjects undergoing bariatric surgery were included in this study. Liver biopsies were obtained to measure hepatic triglyceride and free cholesterol contents, as well as ABCA1, ABCG1, CROT, HADHB, TLR2, miR-33a/b and miR-144 expression. RESULTS: Hepatic free cholesterol content was significantly increased in NASH as compared to non-NASH subjects, while ABCA1 and ABCG1 protein levels significantly decreased with NASH and fibrosis progression. The relative expression of miR-33a and miR-144 correlated inversely with ABCA1 but not with ABCG1 protein levels. Moreover, both miRNAs increased significantly in NASH individuals. miR-33 target genes CROT and HADHB correlated inversely with miR-33a. However, the expression of these genes was not associated with NASH. CONCLUSIONS: miR-33a/144 and their target gene ABCA1 may contribute to the pathogenesis of NASH in morbidly obese subjects.