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.

Gut Microbiota Contribution to Weight-Independent Glycemic Improvements after Gastric Bypass Surgery.

Roux-en-Y gastric bypass surgery (RYGB) leads to improved glycemic control in individuals with severe obesity beyond the effects of weight loss alone. Here, We addressed the potential contribution of gut microbiota in mediating this favourable surgical outcome by using an established preclinical model of RYGB. 16S rRNA sequencing revealed that RYGB-treated Zucker fatty rats had altered fecal composition of various bacteria at the phylum and species levels, including lower fecal abundance of an unidentified Erysipelotrichaceae species, compared with both sham-operated (Sham) and body weight-matched to RYGB-treated (BWM) rats. Correlation analysis further revealed that fecal abundance of this unidentified Erysipelotrichaceae species linked with multiple indices of glycemic control uniquely in RYGB-treated rats. Sequence alignment of this Erysipelotrichaceae species identified Longibaculum muris to be the most closely related species, and its fecal abundance positively correlated with oral glucose intolerance in RYGB-treated rats. In fecal microbiota transplant experiments, the improved oral glucose tolerance of RYGB-treated compared with BWM rats could partially be transferred to recipient germfree mice, independently of body weight. Unexpectedly, providing L. muris as a supplement to RYGB recipient mice further improved oral glucose tolerance, while administering L. muris alone to chow-fed or Western style diet-challenged conventionally raised mice had minimal metabolic impact. Taken together, our findings provide evidence that the gut microbiota contributes to weight loss-independent improvements in glycemic control after RYGB and demonstrate how correlation of a specific gut microbiota species with a host metabolic trait does not imply causation. IMPORTANCE Metabolic surgery remains the most effective treatment modality for severe obesity and its comorbidities, including type 2 diabetes. Roux-en-Y gastric bypass (RYGB) is a commonly performed type of metabolic surgery that reconfigures gastrointestinal anatomy and profoundly remodels the gut microbiota. While it is clear that RYGB is superior to dieting when it comes to improving glycemic control, the extent to which the gut microbiota contributes to this effect remains untested. In the present study, we uniquely linked fecal Erysipelotrichaceae species, including Longibaculum muris, with indices of glycemic control after RYGB in genetically obese and glucose-intolerant rats. We further show that the weight loss-independent improvements in glycemic control in RYGB-treated rats can be transmitted via their gut microbiota to germfree mice. Our findings provide rare causal evidence that the gut microbiota contributes to the health benefits of metabolic surgery and have implications for the development of gut microbiota-based treatments for type 2 diabetes.

Fecal Metabolome and Bacterial Composition in Severe Obesity: Impact of Diet and Bariatric Surgery.

The aim of this study was to monitor the impact of a preoperative low-calorie diet and bariatric surgery on the bacterial gut microbiota composition and functionality in severe obesity and to compare sleeve gastrectomy (SG) versus Roux-en-Y gastric bypass (RYGB). The study also aimed to incorporate big data analysis for the omics results and machine learning by a Lasso-based analysis to detect the potential markers for excess weight loss. Forty patients who underwent bariatric surgery were recruited (14 underwent SG, and 26 underwent RYGB). Each participant contributed 4 fecal samples (baseline, post-diet, 1 month after surgery and 3 months after surgery). The bacterial composition was determined by 16S rDNA massive sequencing using MiSeq (Illumina). Metabolic signatures associated to fecal concentrations of short-chain fatty acids, amino acids, biogenic amines, gamma-aminobutyric acid and ammonium were determined by gas and liquid chromatography. Orange 3 software was employed to correlate the variables, and a Lasso analysis was employed to predict the weight loss at the baseline samples. A correlation between Bacillota (formerly Firmicutes) abundance and excess weight was observed only for the highest body mass indexes. The low-calorie diet had little impact on composition and targeted metabolic activity. RYGB had a deeper impact on bacterial composition and putrefactive metabolism than SG, although the excess weight loss was comparable in the two groups. Significantly higher ammonium concentrations were detected in the feces of the RYGB group. We detected individual signatures of composition and functionality, rather than a gut microbiota characteristic of severe obesity, with opposing tendencies for almost all measured variables in the two surgical approaches. The gut microbiota of the baseline samples was not useful for predicting excess weight loss after the bariatric process.

Investigating the human jejunal microbiota.

Descriptions of the small intestinal microbiota are deficient and conflicting. We aimed to get a reliable description of the jejunal bacterial microbiota by investigating samples from two separate jejunal segments collected from the luminal mucosa during surgery. Sixty patients with morbid obesity selected for elective gastric bypass surgery were included in this survey. Samples collected by rubbing a swab against the mucosa of proximal and mid jejunal segments were characterized both quantitatively and qualitatively using a combination of microbial culture, a universal quantitative PCR and 16S deep sequencing. Within the inherent limitations of partial 16S sequencing, bacteria were assigned to the species level. By microbial culture, 53 patients (88.3%) had an estimated bacterial density of < 1600 cfu/ml in both segments whereof 31 (51.7%) were culture negative in both segments corresponding to a bacterial density below 160 cfu/ml. By quantitative PCR, 46 patients (76.7%) had less than 104 bacterial genomes/ml in both segments. The most abundant and frequently identified species by 16S deep sequencing were associated with the oral cavity, most often from the Streptococcus mitis group, the Streptococcus sanguinis group, Granulicatella adiacens/para-adiacens, the Schaalia odontolytica complex and Gemella haemolysans/taiwanensis. In general, few bacterial species were identified per sample and there was a low consistency both between the two investigated segments in each patient and between patients. The jejunal mucosa of fasting obese patients contains relatively few microorganisms and a core microbiota could not be established. The identified microbes are likely representatives of a transient microbiota and there is a high degree of overlap between the most frequently identified species in the jejunum and the recently described ileum core microbiota.

The Effects of One Anastomosis Gastric Bypass Surgery on the Gastrointestinal Tract.

One anastomosis gastric bypass (OAGB) is an emerging bariatric procedure, yet data on its effect on the gastrointestinal tract are lacking. This study sought to evaluate the incidence of small-intestinal bacterial overgrowth (SIBO) following OAGB; explore its effect on nutritional, gastrointestinal, and weight outcomes; and assess post-OABG occurrence of pancreatic exocrine insufficiency (PEI) and altered gut microbiota composition. A prospective pilot cohort study of patients who underwent primary-OAGB surgery is here reported. The pre-surgical and 6-months-post-surgery measurements included anthropometrics, glucose breath-tests, biochemical tests, gastrointestinal symptoms, quality-of-life, dietary intake, and fecal sample collection. Thirty-two patients (50% females, 44.5 ± 12.3 years) participated in this study, and 29 attended the 6-month follow-up visit. The mean excess weight loss at 6 months post-OAGB was 67.8 ± 21.2%. The glucose breath-test was negative in all pre-surgery and positive in 37.0% at 6 months (p = 0.004). Positive glucose breath-test was associated with lower reported dietary intake and folate levels and higher vitamin A deficiency rates (p ≤ 0.036). Fecal elastase-1 test (FE1) was negative for all pre-surgery and positive in 26.1% at 6 months (p = 0.500). Both alpha and beta diversity decreased at 6 months post-surgery compared to pre-surgery (p ≤ 0.026). Relatively high incidences of SIBO and PEI were observed at 6 months post-OAGB, which may explain some gastrointestinal symptoms and nutritional deficiencies.

Changes in the gut microbiota of morbidly obese patients after laparoscopic sleeve gastrectomy.

Aims: Permanent treatment of morbid obesity with medication or diet is nearly impossible. Laparoscopic sleeve gastrectomy (LSG) is becoming a widely accepted treatment option. This study profiled and compared gut microbiota composition before and after LSG. Methods & results: A total of 54 stool samples were collected from 27 morbidly obese individuals before and after LSG. The gut microbiota was profiled with 16S amplicon sequencing. After LSG, patients demonstrated a significant decrease (p < 0.001) in BMI and an increase in bacterial diversity. An increased Firmicutes/Bacteroidetes ratio was also noticed after LSG. The families Prevotellaceae and Veillonellaceae predominated in preoperative samples but were markedly lowered after LSG. A marked increase in Akkermansia, Alistipes, Streptococcus, Ruminococcus and Parabacteroides was observed after LSG. Conclusion: In addition to lowering BMI, LSG remodeled gut microbiota composition.

Influence of Factors Altering Gastric Microbiota on Bariatric Surgery Metabolic Outcomes.

Little is known about the influence of gastric microbiota on host metabolism, even though the stomach plays an important role in the production of hormones involved in body weight regulation and glucose homeostasis. Proton pump inhibitors (PPIs) and Helicobacter pylori alter gut microbiota, but their impact on gastric microbiota in patients with obesity and the influence of these factors on the metabolic response to bariatric surgery is not fully understood. Forty-one subjects with morbid obesity who underwent sleeve gastrectomy were included in this study. The H. pylori group was established by the detection of H. pylori using a sequencing-based method (n = 16). Individuals in whom H. pylori was not detected were classified according to PPI treatment. Gastric biopsy specimens were obtained during surgery and were analyzed by a high-throughput-sequencing method. Patients were evaluated at baseline and 3, 6, and 12 months after surgery. ß-Diversity measures were able to cluster patients according to their gastric mucosa-associated microbiota composition. H. pylori and PPI treatment are presented as two important factors for gastric mucosa-associated microbiota. H. pylori reduced diversity, while PPIs altered ß-diversity. Both factors induced changes in the gastric mucosa-associated microbiota composition and its predicted functions. PPI users showed lower percentages of change in the body mass index (BMI) in the short term after surgery, while the H. pylori group showed higher glucose levels and lower percentages of reduction in body weight/BMI 1 year after surgery. PPIs and H. pylori colonization could modify the gastric mucosa-associated microbiota, altering its diversity, composition, and predicted functionality. These factors may have a role in the metabolic evolution of patients undergoing bariatric surgery. IMPORTANCE The gut microbiota has been shown to have an impact on host metabolism. In the stomach, factors like proton pump inhibitor treatment and Helicobacter pylori haven been suggested to alter gut microbiota; however, the influence of these factors on the metabolic response to bariatric surgery has not been fully studied. In this study, we highlight the impact of these factors on the gastric microbiota composition. Moreover, proton pump inhibitor treatment and the presence of Helicobacter pylori could have an influence on bariatric surgery outcomes, mainly on body weight loss and glucose homeostasis. Deciphering the relationship between gastric hormones and gastric microbiota and their contributions to bariatric surgery outcomes paves the way to develop gut manipulation strategies to improve the metabolic success of bariatric surgery.

Gut Microbiota and Mycobiota Evolution Is Linked to Memory Improvement after Bariatric Surgery in Obese Patients: A Pilot Study.

Patients with obesity are known to exhibit gut microbiota dysbiosis and memory deficits. Bariatric surgery (BS) is currently the most efficient anti-obesity treatment and may improve both gut dysbiosis and cognition. However, no study has investigated association between changes of gut microbiota and cognitive function after BS. We prospectively evaluated 13 obese patients on anthropometric data, memory functions, and gut microbiota-mycobiota before and six months after BS. The Rey Auditory Verbal Learning Test (AVLT) and the symbol span (SS) of the Weschler Memory Scale were used to assess verbal and working memory, respectively. Fecal microbiota and mycobiota were longitudinally analyzed by 16S and ITS2 rRNA sequencing respectively. AVLT and SS scores were significantly improved after BS (AVLT scores: 9.7 ± 1.7 vs. 11.2 ± 1.9, p = 0.02, and SS scores: 9.7 ± 23.0 vs. 11.6 ± 2.9, p = 0.05). An increase in bacterial alpha-diversity, and Ruminococcaceae, Prevotella, Agaricus, Rhodotorula, Dipodascus, Malassezia, and Mucor were significantly associated with AVLT score improvement after BS, while an increase in Prevotella and a decrease in Clostridium, Akkermansia, Dipodascus and Candida were linked to SS scores improvement. We identified several changes in the microbial communities that differ according to the improvement of either the verbal or working memories, suggesting a complex gut-brain-axis that evolves after BS.

Long-Term Effects of Bariatric Surgery on Gut Microbiota Composition and Faecal Metabolome Related to Obesity Remission.

Obesity is one of the main worldwide public health concerns whose clinical management demands new therapeutic approaches. Bariatric surgery is the most efficient treatment when other therapies have previously failed. Due to the role of gut microbiota in obesity development, the knowledge of the link between bariatric surgery and gut microbiota could elucidate new mechanistic approaches. This study aims to evaluate the long-term effects of bariatric surgery in the faecal metagenome and metabolome of patients with severe obesity. Faecal and blood samples were collected before and four years after the intervention from patients with severe obesity. Biochemical, metagenomic and metabolomic analyses were performed and faecal short-chain fatty acids were measured. Bariatric surgery improved the obesity-related status of patients and significantly reshaped gut microbiota composition. Moreover, this procedure was associated with a specific metabolome profile characterized by a reduction in energetic and amino acid metabolism. Acetate, butyrate and propionate showed a significant reduction with bariatric surgery. Finally, correlation analysis suggested the existence of a long-term compositional and functional gut microbiota profile associated with the intervention. In conclusion, bariatric surgery triggered long-lasting effects on gut microbiota composition and faecal metabolome that could be associated with the remission of obesity.

A microbial signature following bariatric surgery is robustly consistent across multiple cohorts.

Bariatric surgery induces significant shifts in the gut microbiota which could potentially contribute to weight loss and metabolic benefits. The aim of this study was to characterize a microbial signature following Roux-en-Y Gastric bypass (RYGB) surgery using novel and existing gut microbiota sequence data. We generated 16S rRNA gene and metagenomic sequences from fecal samples from patients undergoing RYGB surgery (n = 61 for 16S rRNA gene and n = 135 for metagenomics) at pre-surgical baseline and one, six, and twelve-month post-surgery. We compared these data with three smaller publicly available 16S rRNA gene and one metagenomic datasets from patients who also underwent RYGB surgery. Linear mixed models and machine learning approaches were used to examine the presence of a common microbial signature across studies. Comparison of our new sequences with previous longitudinal studies revealed strikingly similar profiles in both fecal microbiota composition (r = 0.41 ± 0.10; p < .05) and metabolic pathways (r = 0.70 ± 0.05; p < .001) early after surgery across multiple datasets. Notably, Veillonella, Streptococcus, Gemella, Fusobacterium, Escherichia/Shigella, and Akkermansia increased after surgery, while Blautia decreased. Machine learning approaches revealed that the replicable gut microbiota signature associated with RYGB surgery could be used to discriminate pre- and post-surgical samples. Opportunistic pathogen abundance also increased post-surgery in a consistent manner across cohorts. Our study reveals a robust microbial signature involving many commensal and pathogenic taxa and metabolic pathways early after RYGB surgery across different studies and sites. Characterization of the effects of this robust microbial signature on outcomes of bariatric surgery could provide insights into the development of microbiome-based interventions for predicting or improving outcomes following surgery.

Impact of Extreme Obesity and Diet-Induced Weight Loss on the Fecal Metabolome and Gut Microbiota.

SCOPE: A limited number of human studies have characterized fecal microbiota and metabolome in extreme obesity and after diet-induced weight loss. METHODS AND RESULTS: Fecal samples from normal-weight and extremely obese adults and from obese participants before and after moderate diet-induced weight loss are evaluated for their interaction with the intestinal adenocarcinoma cell line HT29 using an impedance-based in vitro model, which reveals variations in the interaction between the gut microbiota and host linked to obesity status. Microbiota composition, short chain fatty acids, and other intestinal metabolites are further analyzed to assess the interplay among diet, gut microbiota, and host in extreme obesity. Microbiota profiles are distinct between normal-weight and obese participants and are accompanied by fecal signatures in the metabolism of biliary compounds and catecholamines. Moderate diet-induced weight loss promotes shifts in the gut microbiota, and the primary fecal metabolomics features are associated with diet and the gut-liver and gut-brain axes. CONCLUSIONS: Analyses of the fecal microbiota and metabolome enable assessment of the impact of diet on gut microbiota composition and activity, supporting the potential use of certain fecal metabolites or members of the gut microbiota as biomarkers for the efficacy of weight loss in extreme obesity.

Immunometabolism, Micronutrients, and Bariatric Surgery: The Use of Transcriptomics and Microbiota-Targeted Therapies.

BACKGROUND: Obesity is associated with the gut microbiota and decreased micronutrient status. Bariatric surgery is a recommended therapy for obesity. It can positively affect the composition of the gut bacteria but also disrupt absorption of nutrients. Low levels of micronutrients can affect metabolic processes, like glycolysis, TCA cycle, and oxidative phosphorylation, that are associated with the immune system also known as immunometabolism. METHODS: MEDLINE, PUBMED, and Google Scholar were searched. Articles involving gut microbiome, micronutrient deficiency, gut-targeted therapies, transcriptome analysis, micronutrient supplementation, and bariatric surgery were included. RESULTS: Studies show that micronutrients play a pivotal role in the intestinal immune system and regulating immunometabolism. Research demonstrates that gut-targeting therapies may improve the microbiome health for bariatric surgery populations. There is limited research that examines the role of micronutrients in modulating the gut microbiota among the bariatric surgery population. CONCLUSIONS: Investigations are needed to understand the influence that micronutrient deficiencies have on the gut, particularly immunometabolism. Nutritional transcriptomics shows great potential in providing this type of analysis to develop gut-modulating therapies as well as more personalized nutrition recommendations for bariatric surgery patients.

Gut Microbiota, Probiotics and Psychological States and Behaviors after Bariatric Surgery-A Systematic Review of Their Interrelation.

The gastrointestinal (GI) microbiota plays an important role in health and disease, including brain function and behavior. Bariatric surgery (BS) has been reported to result in various changes in the GI microbiota, therefore demanding the investigation of the impact of GI microbiota on treatment success. The goal of this systematic review was to assess the effects of BS on the microbiota composition in humans and other vertebrates, whether probiotics influence postoperative health, and whether microbiota and psychological and behavioral factors interact. A search was conducted using PubMed and Web of Science to find relevant studies with respect to the GI microbiota and probiotics after BS, and later screened for psychological and behavioral parameters. Studies were classified into groups and subgroups to provide a clear overview of the outcomes. Microbiota changes were further assessed for whether they were specific to BS in humans through the comparison to sham operated controls in other vertebrate studies. Changes in alpha diversity appear not to be specific, whereas dissimilarity in overall microbial community structure, and increases in the abundance of the phylum Proteobacteria and Akkermansia spp. within the phylum Verrucomicrobia after surgery were observed in both human and other vertebrates studies and may be specific to BS in humans. Human probiotic studies differed regarding probiotic strains and dosages, however it appeared that probiotic interventions were not superior to a placebo for quality of life scores or weight loss after BS. The relationship between GI microbiota and psychological diseases in this context is unclear due to insufficient available data.

Roux-en-Y gastric bypass surgery changes fungal and bacterial microbiota in morbidly obese patients-A pilot study.

The Roux-en-Y gastric bypass (RYGB) remains the most effective treatment for morbidly obese patients to lower body weight and improve glycemic control. There is recent evidence that the mycobiome (fungal microbiome) can aggravate disease severity in a number of diseases including inflammatory bowel disease (IBD), irritable bowel syndrome (IBS) and hepatitis; moreover, a dysbiotic fungal microbiota has been reported in the obese. We characterized fungal and bacterial microbial composition in fecal samples of 16 morbidly obese patients before and three months after RYGB surgery and compared with nine healthy controls. We found that RYGB surgery induced a clear alteration in structure and composition of the gut fungal and bacterial microbiota. Beta diversity analysis revealed significant differences in bacterial microbiota between obese patients before surgery and healthy controls (P < 0.005) and a significant, unidirectional shift in RYGB patients after surgery (P < 0.001 vs. before surgery). In contrast, there was no significant difference in fungal microbiota between groups but individually specific changes after RYGB surgery. Interestingly, RYGB surgery induced a significant reduction in fungal alpha diversity namely Chao1, Sobs, and Shannon diversity index (P<0.05, respectively) which contrasts the trend for uniform changes in bacteria towards increased richness and diversity post-surgery. We did not observe any inter-kingdom relations in RYGB patients but in the healthy control cohort and there were several correlations between fungi and bacteria and clinical parameters (P<0.05, respectively) that warrant further research. Our study identifies changes in intestinal fungal communities in RYGB patients that are distinct to changes in the bacterial microbiota.

Distinct differences in gut microbial composition and functional potential from lean to morbidly obese subjects.

INTRODUCTION: The gut microbiome may contribute to the development of obesity. So far, the extent of microbiome variation in people with obesity has not been determined in large cohorts and for a wide range of body mass index (BMI). Here, we aimed to investigate whether the faecal microbial metagenome can explain the variance in several clinical phenotypes associated with morbid obesity. METHODS: Caucasian subjects were recruited at our hospital. Blood pressure and anthropometric measurements were taken. Dietary intake was determined using questionnaires. Shotgun metagenomic sequencing was performed on faecal samples from 177 subjects. RESULTS: Subjects without obesity (n = 82, BMI 24.7 ± 2.9 kg m-2 ) and subjects with obesity (n = 95, BMI 38.6 ± 5.1 kg m-2 ) could be clearly distinguished based on microbial composition and microbial metabolic pathways. A total number of 52 bacterial species differed significantly in people with and without obesity. Independent of dietary intake, we found that microbial pathways involved in biosynthesis of amino acids were enriched in subjects with obesity, whereas pathways involved in the degradation of amino acids were depleted. Machine learning models showed that more than half of the variance in body fat composition followed by BMI could be explained by the gut microbiome, composition and microbial metabolic pathways, compared with 6% of variation explained in triglycerides and 9% in HDL. CONCLUSION: Based on the faecal microbiota composition, we were able to separate subjects with and without obesity. In addition, we found strong associations between gut microbial amino acid metabolism and specific microbial species in relation to clinical features of obesity.

Alteration in faecal bile acids, gut microbial composition and diversity after laparoscopic sleeve gastrectomy.

BACKGROUND: Laparoscopic sleeve gastrectomy (LSG) is a well established treatment for severe obesity and type 2 diabetes. Although the gut microbiota is linked to the efficacy of LSG, the underlying mechanisms remain elusive. The effect of LSG for morbid obesity on the gut microbiota and bile acids was assessed here. METHODS: Severely obese subjects who were candidates for LSG were included and followed until 6 months after surgery. The composition and abundance of the microbiota and bile acids in faeces were assessed by 16S ribosomal RNA sequencing, quantitative PCR and liquid chromatography-mass spectrometry. RESULTS: In total, 28 patients with a mean(s.d.) BMI of 44·2(6·6) kg/m2 were enrolled. These patients had achieved excess weight loss of 53·2(19·0) per cent and showed improvement in metabolic diseases by 6 months after LSG, accompanied by an alteration in the faecal microbial community. The increase in α-diversity and abundance of specific taxa, such as Rikenellaceae and Christensenellaceae, was strongly associated with reduced faecal bile acid levels. These changes had a significant positive association with excess weight loss and metabolic alterations. However, the total number of faecal bacteria was lower in patients before (mean(s.d.) 10·26(0·36) log10 cells per g faeces) and after (10·39(0·29) log10 cells per g faeces) operation than in healthy subjects (10·83(0·27) log10 cells per g faeces). CONCLUSION: LSG is associated with a reduction in faecal bile acids and greater abundance of specific bacterial taxa and α-diversity that may contribute to the metabolic changes.

ANTECEDENTES: La gastrectomía vertical laparoscópica (laparoscopic sleeve gastrectomy, LSG) es un tratamiento bien establecido para la obesidad grave y la diabetes tipo 2. Aunque la microbiota intestinal se ha vinculado con la eficacia de LSG, los mecanismos subyacentes siguen siendo poco conocidos. En este estudio se evaluó el efecto de LSG en la obesidad mórbida sobre la microbiota del intestino y de los ácidos biliares (bile acids, BA). MÉTODOS: Tras la aprobación del Comité ético y la obtención del consentimiento informado, los sujetos con obesidad grave que eran candidatos para LSG fueron incluidos en el estudio y seguidos durante 6 meses después de la operación. Se evaluaron la composición y abundancia de la microbiota y BA en las heces mediante secuenciación del gen 16S rRNA, PCR cuantitativa y cromatografía líquida-espectrometría de masas. RESULTADOS: En total, 28 pacientes con una mediana (rango) del IMC de 43,9 kg/m2 (35,0-61,9) fueron reclutados y a los 6 meses tras una LSG, consiguieron una pérdida del exceso de peso de 47,3% (20,7-95,1) y mejoría de las enfermedades metabólicas acompañada de una alteración en la comunidad microbiana fecal. El aumento en la diversidad α y abundancia de especies taxonómicas específicas como Rikenellaceae y Christensenellaceae, se asociaba fuertemente con niveles fecales reducidos de BA. Estos cambios se asociaban de manera positiva y significativa con la pérdida del exceso de peso y las alteraciones metabólicas. Sin embargo, el número total de bacterias fecales en los pacientes fue inferior al de los sujetos sanos (10,84 log10 células/g heces (9,46-11,35)) antes de la operación (10,26 log10 células/g heces (9,44-10,91)) y después de la misma (10,42 log10 células/g heces (9,57-10,96)). CONCLUSIÓN: LSG se asoció con menos BA fecal y mayor abundancia de especies bacterianas específicas y diversidad α lo que puede contribuir a los cambios metabólicos.

Comparison of methodological approaches to human gut microbiota changes in response to metabolic and bariatric surgery: A systematic review.

Substantial differences in the response of gut microbial composition to metabolic and bariatric surgery have been reported. Therefore, the goal of the present review is to evaluate if methodological differences could be driving this lack of consistency. A search was conducted using PUBMED, Web of Science, Science Direct and COCHRANE using the following inclusion criteria: human studies written in English with a baseline sampling point, using gut microbiota as an outcome and either Roux-n-Y gastric bypass or sleeve gastrectomy. Sixteen articles were selected (total 221 participants). Roux-n-Y gastric bypass caused more alterations in gut microbial composition in comparison with sleeve gastrectomy. Substantial variability was found in study designs, data collection and analyses across studies. Increases in several families and genera from the phylum Proteobacteria and Bacteroidetes, the family Streptococcaceae, the species Akkermansia muciniphila and Streptococcus salivarius and a decrease in the phylum Firmicutes and the family Bifidobacteriaceae were reported. There is a need for standardization not only of microbial analysis but also of study designs when analysing the effect of bariatric surgery on the human gut microbiome. In addition, outcomes from different surgical procedures should not be combined as they produce distinctive effects on gut microbial composition.

Gut Microbiota Profile of Obese Diabetic Women Submitted to Roux-en-Y Gastric Bypass and Its Association with Food Intake and Postoperative Diabetes Remission.

Gut microbiota composition is influenced by environmental factors and has been shown to impact body metabolism. OBJECTIVE: To assess the gut microbiota profile before and after Roux-en-Y gastric bypass (RYGB) and the correlation with food intake and postoperative type 2 diabetes remission (T2Dr). DESIGN: Gut microbiota profile from obese diabetic women was evaluated before (n = 25) and 3 (n = 20) and 12 months (n = 14) after RYGB, using MiSeq Illumina-based V4 bacterial 16S rRNA gene profiling. Data on food intake (7-day record) and T2Dr (American Diabetes Association (ADA) criteria) were recorded. RESULTS: Preoperatively, the abundance of five bacteria genera differed between patients with (57%) and without T2Dr (p < 0.050). Preoperative gut bacteria genus signature was able to predict the T2Dr status with 0.94 accuracy ROC curve (receiver operating characteristic curve). Postoperatively (vs. preoperative), the relative abundance of some gut bacteria genera changed, the gut microbial richness increased, and the Firmicutes to Bacteroidetes ratio (rFB) decreased (p < 0.05) regardless of T2Dr. Richness levels was correlated with dietary profile pre and postoperatively, mainly displaying positive and inverse correlations with fiber and lipid intakes, respectively (p < 0.05). CONCLUSIONS: Gut microbiota profile was influenced by RYGB and correlated with diet and T2Dr preoperatively, suggesting the possibility to assess its composition to predict postoperative T2Dr.

Intrahepatic bacterial metataxonomic signature in non-alcoholic fatty liver disease.

OBJECTIVE: We aimed to characterise the liver tissue bacterial metataxonomic signature in two independent cohorts of patients with biopsy-proven non-alcoholic fatty liver disease (NAFLD) diagnosis, as differences in the host phenotypic features-from moderate to severe obesity-may be associated with significant changes in the microbial DNA profile. DESIGN AND METHODS: Liver tissue samples from 116 individuals, comprising of 47 NAFLD overweight or moderately obese patients, 50 NAFLD morbidly obese patients elected for bariatric surgery and 19 controls, were analysed using high-throughput 16S rRNA gene sequencing. RESULTS: Liver bacterial DNA profile significantly differs between morbidly obese and non-morbidly obese patients with NAFLD. Bacteroidetes (p=1.8e-18) and Firmicutes (p=0.0044) were over-represented in morbidly obese patients and Proteobacteria (p=5.2e-10)-specifically Gammaproteobacteria and Alphaproteobacteria, and Deinococcus-Thermus (p=0.00012)-were over-represented in the non-morbidly obese cohort. Cohort-specific analysis of liver microbial DNA signatures shows patterns linked to obesity. The imbalance in Proteobacteria (Alpha or Gamma) among non-morbidly obese patients, and Peptostreptococcaceae, Verrucomicrobia, Actinobacteria and Gamma Proteobacteria DNA among morbidly obese patients was associated with histological severity. Decreased amounts of bacterial DNA from the Lachnospiraceae family were associated with more severe histological features. Proteobacteria DNA was consistently associated with lobular and portal inflammation scores. Microbial DNA composition corresponded to predicted functional differences. CONCLUSION: This is the first comprehensive study showing that the liver tissue of NAFLD patients contains a diverse repertoire of bacterial DNA (up to 2.5×104 read counts). The liver metataxonomic signature may explain differences in the NAFLD pathogenic mechanisms as well as physiological functions of the host.

Changes in the intestinal microbiota of superobese patients after bariatric surgery.

OBJECTIVES: The gut microbiota is associated with obesity and weight loss after bariatric surgery and has been related to its changing pattern. Exactly how the bacterial population affects weight loss and the results of surgery remain controversial. This study aimed to evaluate the intestinal microbiota of superobese patients before and after gastric bypass surgery (RYGB). METHOD: DNA fragments for the microbiota obtained from stool samples collected from nine superobese patients before and after bariatric surgery were sequenced using Ion Torrent. RESULTS: We observed that with a mean follow-up of 15 months, patients achieved 55.9% excess weight loss (EWL). A significant population reduction in the Proteobacteria phylum (11 to 2%, p=0.0025) was observed after surgery, while no difference was seen in Firmicutes and Bacteroidetes. Further analyses performed with two specific individuals with divergent clinical outcomes showed a change in the pattern between them, with a significant increase in Firmicutes and a decrease in Bacteroidetes in the patient with less weight loss (%EWL 50.79 vs. 61.85). CONCLUSIONS: RYGB affects the microbiota of superobese patients, with a significant reduction in Proteobacteria in patients with different weight loss, showing that different bacteria may contribute to the process.