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 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.

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.

Gut Microbiota Imbalance Can Be Associated with Non-malabsorptive Small Bowel Shortening Regardless of Blind Loop.

INTRODUCTION: Some traditional bariatric surgery procedures may lead to functional gut shortening, which may unsettle the fine-tuned gastrointestinal physiology and affect gut microbiota balance. PURPOSE: Evaluate the gut microbiota behavior in rat models facing gut shortening due to intestinal bypass. MATERIALS AND METHODS: Wistar rats (n = 17) were randomly distributed in three groups: (1) sham group (n = 5); (2) blind loop group (n = 6); and (3) resection group (n = 6). Intestinal samples and feces were analyzed to measure bacterial concentrations (small intestinal bacterial overgrowth-SIBO) 12 weeks after the experimental procedures. Bacterial translocation (BT) was investigated in the mesenteric lymph node (MLN), liver, spleen, and lung of the animals. In addition, inflammatory aspects were investigated in their liver and small bowel through histological analysis. RESULTS: Regardless of blind loop, gut shortening groups recorded similar high level of bacterial concentrations in intestine compartments, greater than that of the sham group (p ≤ 0.05). BT was only observed in the MLN of gut shortening models, with higher percentage in the blind loop group (p ≤ 0.05). The gut and liver histopathological analysis showed similar low-grade chronic inflammation in both gut shortening groups, likely associated with SIBO/BT events. CONCLUSION: Sustained SIBO/BT was associated with proximal gut shortening in half regardless of blind loop, whereas the GI tract's ability to restore gut microbiota balance after a surgical challenge on the small bowel appears to be linked to the functional remaining gut.

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.

Epithelial cell turnover is increased in the excluded stomach mucosa after Roux-en-Y gastric bypass for morbid obesity.

BACKGROUND: Mucosal alterations after Roux-en-Y gastric bypass for morbid obesity have not been clearly evaluated. This study aims to analyze the mucosal alterations (proliferative status (Ki-67); apoptosis (caspase-3 and BCL-2); hormonal function (gastrin)) in the excluded stomach. METHODS: Double-balloon enteroscopy was performed in 35 patients who underwent Roux-en-Y gastric bypass longer than 36 months. Multiple biopsies of the proximal pouch and the excluded gastric mucosa were collected. Gastric biopsies from 32 non-operated obese patients were utilized as controls. Endoscopic biopsies were cut from tissue blocks fixed in formalin and embedded in paraffin. Sections 4 µm thick were examined for immunoexpression using the streptavidin-biotin-peroxidase method. RESULTS: The two groups were comparable for age, gender, gastritis, intestinal metaplasia, and Helicobacter pylori. The mean number of positive gastrin cells was 55.5 (standard deviation (SD) = 11.7) in the control group and 29.6 (SD = 7.9) in the cases, p = 0.0003. Ki-67 proliferative index in cases (body = 24.7%, antrum = 24.9%) was significantly higher compared to controls (body = 15.0% and antrum = 17.7%), p = 0.002 and 0.01, respectively. Caspase-3 immunoexpression was higher in the controls compared to the excluded stomach (46 vs. 31%), p = 0.02. There was no statistical difference between CD3, CD8, and Bcl-2 immunoexpressions in the control and cases. CONCLUSIONS: Cell proliferation is increased and apoptosis is downregulated in the excluded gastric mucosa compared to the non-operated obese controls. Alterations in cell turnover and in hormonal secretions in these conditions may be of relevance in long-term follow-up.

Increased gastric cytokine production after Roux-en-Y gastric bypass for morbid obesity.

HYPOTHESIS: Mucosal cytokines may be involved in the process of gastric bacterial contamination that may occur after Roux-en-Y bypass for morbid obesity in both gastric chambers, with inflammation and gastritis mostly in the excluded stomach. DESIGN: A prospective observational study in a homogeneous population with nonspecific complaints. SETTING: Outpatient clinic of a large, public, academic hospital. PATIENTS: Subjects (n = 37; 26 [70.3%] female; mean +/- SD age, 42.4 +/- 9.9 years) seen a mean +/- SD of 7.3 +/- 1.4 years after Roux-en-Y gastric bypass and nonoperated on morbidly obese control subjects (n = 10; 7 [70%] female; mean +/- SD age, 44.0 +/- 8.9 years). INTERVENTION: Enteroscopy was performed to collect samples for cytokine assays and bacteriologic studies. MAIN OUTCOME MEASURES: Concentrations of tumor necrosis factor alpha and transforming growth factor beta in the gastric mucosa of both chambers in patients undergoing Roux-en-Y gastric bypass and correlation with bacterial overgrowth and Helicobacter pylori infection. RESULTS: High microbial counts (>10(5) colony-forming units per milliliter) were detected in 22 (59.5%) and 7 (18.9%) of the 37 samples from the functional pouch and excluded reservoir, respectively; and H pylori investigation was positive in 6 of 37 samples (16.2%). The tumor necrosis factor alpha concentration (mean +/- SD, 2.1 +/- 1.9 pg/g of protein) and the transforming growth factor beta concentration (mean +/- SD, 24.2 +/- 12.8 pg/g of protein) in the excluded stomach, but not in the proximal pouch, were elevated with regard to the corpus or antrum of controls, and correlation with bacterial overgrowth and with H pylori infection was demonstrated. CONCLUSION: Overexpression of tumor necrosis factor alpha and transforming growth factor beta occurred in the distal stomach, positive cytokine correlation with microbial invasion by H pylori and nonspecific germs was seen, and further studies addressing phenotypic and genotypic changes of gastric mucosa are recommended.

Microbial flora of the stomach after gastric bypass for morbid obesity.

BACKGROUND: The normal stomach is virtually sterile but the effect of Roux-en-Y gastric bypass (RYGBP) on bacterial flora in the used (very small proximal pouch) and unused (large bypassed) gastric chambers is not known. In a prospective study, this variable was documented. METHODS: Bariatric subjects (n=37) were submitted to endoscopic examination of both gastric reservoirs via FUJINON enteroscope model EN-450P5, 7.3 +/- 1.4 years after RYGBP. Age was 42.4 +/- 9.9 years (70.2% females), preoperative BMI was 53.5 +/- 10.6, and current BMI was 32.6 +/- 7.8 kg/m2. Methods included quantitative culture of gastric secretion along with gastric pH and lactulose/hydrogen breath test. RESULTS: None of the subjects displayed diarrhea, malabsorption or other complaints suggestive of GI bacterial overgrowth. Elevated counts of bacteria and fungi were identified in both chambers, with predominance of aerobes and anaerobes, but not molds and yeasts, in the proximal stomach. Gram-positive cocci, bacilli and coccobacilli represented the majority of the isolates. Gastric pH was neutral (pH 7.0 +/- 0.2) in the proximal pouch, whereas the distal chamber mostly but not always conserved the expected acidity (pH 3.3 +/- 2.2, P<0.001). The breath test for bacterial overgrowth was positive in 40.5% of the population. CONCLUSIONS: 1) Frequent colonization of both gastric chambers was detected; 2) Aerobes, anaerobes and fungi were represented in both situations; 3) Gastric pH as well as bacterial count was higher in the functioning proximal stomach; 4) Breath test was positive in 40.5% of the subjects; 5) Clinical manifestation such as diarrhea, malabsorption or pneumonia were not demonstrated; 6) Further histologic and microbiologic studies of both the stomach and the small bowel are recommended.

What to expect in the excluded stomach mucosa after vertical banded Roux-en-Y gastric bypass for morbid obesity.

Mucosal alterations after vertical banded Roux-en-Y gastric bypass have not been clearly evaluated. The aim of this paper was to analyze the histological findings and the presence of Helicobacter pylori in the excluded stomach. Forty consecutive patients who underwent Roux-en-Y gastric bypass longer than 36 months were selected for double-balloon enteroscopy. The excluded stomach was reached in 35/40 patients (88%). Morphological alterations were analyzed through hematoxilin and eosin and the presence of H. pylori was confirmed with Giemsa staining. Thirty patients (86%) were female, and the mean age was 43 years old. The mean postoperative time was 78 months (36-110 months). Histologically, all patients had chronic gastritis in the bypassed stomach, with pangastritis in 33/35 (94%). Five cases (5/35, 14%) presented atrophy and four of them also had intestinal metaplasia. Helicobacter pylori was detected in 7/35 (20%) of the excluded stomach and in 12/35 (34%) of the functional pouch. All patients positive for H. pylori in the excluded stomach were also positive in the functional pouch, p = 0.0005. Helicobacter pylori is still present in the excluded stomach after Roux-en-Y gastric bypass and might be considered for treatment. Histological findings indicated high prevalence of atrophy and intestinal metaplasia in this selected population.