Abdominal Pain After Bariatric Surgery and the Role of the Gut: A Review.

Objective: This paper reviews the prevalence, etiology, risk factors, diagnosis and prevention of chronic abdominal pain after bariatric surgery. Introduction: Chronic pain is a very common and complex problem that has serious consequences on individuals and society. It frequently presents as a result of a disease or an injury. Obesity and obesity-related comorbidities are a major health problem and are dramatically increasing year after year. Dieting and physical exercise show disappointing results in the treatment of obesity. Therefore, bariatric surgery is increasingly widely offered as a weight reducing strategy. In our pain clinic we see a lot of patients who suffer from chronic abdominal pain after bariatric surgery. This review aims to explore the link between chronic abdominal pain and bariatric surgery in this specific type of patients. Method: The review is based on searches in PubMed, Embase and Cochrane databases. Keywords are used in different combinations. We did a cross-reference of the articles included. Results: Chronic abdominal pain after bariatric surgery is very common. Around 30% of the bariatric patients experience persistent abdominal pain. An explanation for the abdominal pain is found in 2/3 of these patients. There is a wide variety of causes including behavioral and nutritional disorders, functional motility disorders, biliary disorders, marginal ulceration and internal hernia. Another, frequently overlooked, cause is abdominal wall pain. Unexplained abdominal pain after bariatric surgery is present in 1/3 of the patients with persistent abdominal pain. More studies are needed on the risk factors and prevention of unexplained abdominal pain in bariatric patients.

Nonalcoholic fatty liver disease (NAFLD) is increasing in parallel with the rising prevalence of obesity, leading to major health and socioeconomic consequences. To date, the most effective therapeutic approach for NAFLD is weight loss. Accordingly, bariatric surgery (BS), which produces marked reductions in body weight, is associated with significant histopathological improvements in advanced stages of NAFLD, such as nonalcoholic steatohepatitis (NASH) and liver fibrosis. BS is also associated with substantial taxonomical and functional alterations in gut microbiota, which are believed to play a significant role in metabolic improvement after BS. Interestingly, gut microbiota and related metabolites may be implicated in the pathogenesis of NAFLD through diverse mechanisms, including specific microbiome signatures, short chain fatty acid production or the modulation of one-carbon metabolism. Moreover, emerging evidence highlights the potential association between gut microbiota changes after BS and NASH resolution. In this review, we summarize the current knowledge on the relationship between NAFLD severity and gut microbiota, as well as the role of the gut microbiome and related metabolites in NAFLD improvement after BS.

Unexplained abdominal pain in morbidly obese patients after bariatric surgery

In recent years, bariatric surgery has emerged as a promising treatment for type 2 diabetes. Bariatric surgery is known to cause alterations in the relative abundance and composition of gut microbiota, which may lead to alterations in the levels of Short-Chain Fatty Acids (SCFAs) that are produced during fermentation by gut microbes. However, little is known about the mechanism of improved glucose metabolism mediated by gut microbiota following bariatric surgery. The aim of our study was to explore whether changes in gut microbiota and in fecal SCFA could be detected following single-anastomosis duodenal jejunal bypass (DJB-sa) surgery, a type of bariatric surgery, and whether these alterations might be related to the improvement of glucose metabolism. To this end, we performed DJB-sa or SHAM surgery on Goto-Kakisaki (GK) rats. We then compared the glucose metabolism as well as changes in gut microbiota and SCFAs levels between both groups. Our results showed that DJB-sa surgery was associated with a significant decrease in fasting blood glucose (FBG), intraperitoneal glucose tolerance test (IPGTT), and fasting serum insulin (FSI). And, DJB-sa led to a change in the composition of gut microbiota including an increase in the relative abundance of SCFA-producing bacteria (Bifidobacterium and Subdoligranulum). Moreover, the levels of six SCFAs in feces, as well as the intestinal expression of SCFA receptors including G-protein-coupled receptor 41 (GPR41), G-protein-coupled receptor 43 (GPR43), and G-protein-coupled receptor 109A (GPR109A), and the expression of Glucagon-like peptide-1 (GLP-1) displayed a significant increase following DJB-sa compared with the Sham group. Thus, the gut microbiota may contribute to the improvement of glucose metabolism in type 2 diabetes following DJB-sa. In conclusion, our study shows that DJB-sa improves glucose metabolism by modulating gut microbiota and by increasing short-chain fatty acid production.

Bariatric surgery in morbid obesity, either through sleeve gastrectomy (SG) or Roux-Y gastric bypass (RYGB), leads to sustainable weight loss, improvement of metabolic disorders and changes in intestinal microbiota. Yet, the relationship between changes in gut microbiota, weight loss and surgical procedure remains incompletely understood. We determined temporal changes in microbiota composition in 45 obese patients undergoing crash diet followed by SG (n = 22) or RYGB (n = 23). Intestinal microbiota composition was determined before intervention (baseline, S1), 2 weeks after crash diet (S2), and 1 week (S3), 3 months (S4) and 6 months (S5) after surgery. Relative to S1, the microbial diversity index declined at S2 and S3 (p < 0.05), and gradually returned to baseline levels at S5. Rikenellaceae relative abundance increased and Ruminococcaceae and Streptococcaceae abundance decreased at S2 (p < 0.05). At S3, Bifidobacteriaceae abundance decreased, whereas those of Streptococcaceae and Enterobacteriaceae increased (p < 0.05). Increased weight loss between S3-S5 was not associated with major changes in microbiota composition. No significant differences appeared between both surgical procedures. In conclusion, undergoing a crash diet and bariatric surgery were associated with an immediate but temporary decline in microbial diversity, with immediate and permanent changes in microbiota composition, independent of surgery type.

Obesity is a multi-factorial disease linked to various metabolic disorders, including insulin resistance, type-2 diabetes (T2D) and cardiovascular diseases. Traditional treatments often show limited long-term success, while bariatric surgery has emerged as the most effective intervention for sustained weight loss and comorbidity improvement. Alterations in gut microbiota may significantly contribute to these metabolic improvements. This systematic review wasaimed at evaluating changes in gut microbiota composition before and after bariatric surgery and their association with clinical outcomes, including weight loss, insulin sensitivity and lipid metabolism. Followingthe Preferred Reporting Items for SystematicReviews and Meta-Analyses (PRISMA)guidelines, a comprehensive search of PubMed, Scopus, Web of Science and clinicaltrials.gov databases was conducted for studies published between 2004 and 2024. Keywords included "bariatric surgery," "gut microbiota" and "obesity." Inclusion criteria focused on human studies with pre and post-surgical microbiota analysis. Non-human studies, pediatric populations and studies without microbiota assessment were excluded. Data extraction covered microbiota profiles, metabolic outcomes and clinical markers. Total 27 articles and 28 clinical trials met the inclusion criteria. Pre-surgery, obese patients exhibited dysbiosis characterized by reduced microbial diversity and imbalances in key bacterial phyla. Post-surgery, especially after Roux-en-Y gastric bypass (RYGB) and sleeve gastrectomy (SG), patients showed increased microbial diversity, reduced Firmicutes and elevated beneficial bacteria such asAkkermansia muciniphila and short-chain fatty acid (SCFA) producing bacteria. These microbiota changes were correlated with significant improvements in weight loss, insulin sensitivity and lipid profiles. However, some studies reported inconsistent or modest microbiota changes. Bariatric surgery leads to significant gut microbiota alterations that are closely linked to metabolic improvements, including enhanced glucose control and lipid metabolism. However, the long-term sustainability of these microbial changes remains unclear. Longitudinal studies are essential to determine whether these alterations persist over time and how they continuously impact metabolic health. Further research should explore targeted microbiota interventions to maintain beneficial microbial profiles post-surgery.

Altered gut microbiota trigger weight loss Changes in the gut microbiota are partially responsible for the weight loss and reduced adiposity observed in mice following Roux-en-Y gastric bypass (RYGB) surgery, shows a recent study in Science Translational Medicine. RYGB surgery restricts food intake and alters metabolism. In addition, this procedure causes a shift in the gut microbiota, but the contribution of the altered microbial community to RYGB outcomes is unclear. Liou et al. hypothesized that because the gut microbiota and RYGB influence similar metabolic parameters, changes in gut microbiota could have a role in the metabolic benefits resulting from bariatric surgery. The investigators used an RYGB mouse model to examine whether changes in gut microbiota after RYGB are conserved among humans and rodents, and to identify the potential mechanisms underlying weight and adipose tissue loss. The researchers examined the gut microbial community before and weekly over 3 months after RYGB surgery and compared it with that of sham-operated ad-libitum-fed mice and with that of weight-matched sham-operated control mice. Analysis of faecal samples, by 16S ribosomal RNA gene sequencing, showed that RYGB led to a rapid (within 1 week) and sustained modification of the gut microbiota. A substantial increase in the amount of verrucomicrobia (Akkermansia) and gammaproteobacteria (Escherichia) was seen in faecal samples from RYGB-treated mice, which is similar to the microbial changes found in human patients after gastric bypass surgery. Transfer of caecal contents from RYGBtreated and control mice to nonoperated, germ-free mice led to a marked reduction in body weight and fat deposition in animals receiving the RYGB microbiota. Moreover, the RYGB-associated changes in gut microbiota were independent of dietary composition and weight change. The mechanisms behind the microbialinduced changes in metabolism are unclear, although the researchers suggest that by-products from microbial fermentation, short-chain fatty acids, could affect host physiology. Identifying the key metabolic pathways is the next important step to understanding how the gut microbiota shapes energy balance and the metabolic response to surgical intervention, the authors conclude.

Obesity is associated with altered gut microbiota and low-grade inflammation. A key factor in the inflammatory process is endotoxin lipopolysaccharide (LPS). Plasma LPS levels and sensory agent lipopolysaccharide-binding protein (LBP) are shown to be elevated in obesity. This elevation may be due to increased intestinal permeability and incorporation of a high-fat diet accompanied by overfeeding. Bariatric surgery has become a popular treatment option that results in stable weight loss and improvement of obesity-related conditions. Studies outlined in this review show reduced LPS and LBP levels after different bariatric procedures. LPS receptor CD14 and mRNA expression toll-like receptor 2 (TLR2) and toll-like receptor 4 (TLR4) were also shown to have reduced levels following surgery. Changes in LPS and LPS components after bariatric surgery are shown to be linked to the surgical technique of the procedure and restriction of caloric intake. Additionally, changes in the gut microbiota provide some insight to the reduction of inflammatory markers after surgery. The beneficial effects of bariatric surgery are not dependent on weight loss alone. The inflammatory pathway plays a key role in the improvement of metabolic complications following surgery that should be further examined. Additional research is needed to evaluate short- and long-term changes of LPS and LPS components after bariatric surgery, including how those assessments can be applied to clinical practice.

Objective To explore the incidence, clinical features, causes, treatment method and risk factors of 30-day readmission after bariatric and metabolic surgery. Methods The retrospective case-control study was conducted. The clinical data of 631 obese patients who underwent bariatric and metabolic surgery in the First Affiliated Hospital of Nanjing Medical University from May 2010 to May 2016 were collected. All the 631 patients underwent laparoscopic sleeve gastrectomy (LSG) or laparoscopic Roux-en-Y gastric bypass (LRYGB). Patients were followed up by outpatient examination and telephone interview for 1 month to detect readmission of patients up to June 2016. Observation indicators: (1) 30-day readmission situations after bariatric and metabolic surgery: cases with readmission, readmission time, clinical features, causes and treatment of readmission; (2) risk factors analysis affecting 30-day readmission after bariatric and metabolic surgery. Measurement data with skewed distribution were described as M (range). The univariate analysis and multivariate analysis were respectively done using the chi-square test and Logistic regression model. Results (1) Thirty-day readmission situations after bariatric and metabolic surgery: among 631 patients receiving postoperative 1-months follow-up, 21 had 30-day readmission, with an incidence of 3.33%(21/631), including 13 males and 8 females; 10 received LSG and 11 received LRYGB. The median readmission time of 21 patients was 12 days (range, 4-30 days). Of 21 patients, nausea, vomiting and dehydration of the main manifestations were detected in 11 patients, gastrointestinal bleeding in 6 patients, high fever in 2 patients, bowel obstruction in 1 patient and abdominal pain in 1 patient. The causes of the readmission of 21 patients: 8 had improper food intake including 5 with premature solid food intake, 1 with premature semi-fluid food intake, 1 with irritating food intake and 1 with swallowing whole tablets; 3 had postoperative over-anxiety; 1 had Petersen hiatal hernia; 1 had anastomotic ulcer; 1 had anastomotic edema; 1 had abdominal abscess. Of 6 patients with uncertain causes, 4 had gastrointestinal bleeding and didn't receive endoscopy; 1 had postoperative unexplained abdominal pain and underwent laboratory and imaging examinations and gastroscopy, showing no trouble finding; 1 had high fever, and no abnormality was detected by imaging examination. Of 21 patients, 19 underwent conservative treatment (rehydration and acid suppression) and then discharged from hospital after improvement, without readmission; 1 with abdominal abscess was cured after emergency debridement and drainage; 1 with Petersen hiatal hernia was cured by emergency surgery. The median duration of hospital stay in 21 patients with readmission was 7 days (range, 3-40 days). (2) Risk factors analysis affecting 30-day readmission after bariatric and metabolic surgery: the results of univariate analysis showed that gender, preoperative adephagia habit and duration of postoperative hospital stay were related factors affecting 30-day readmission after bariatric and metabolic surgery (χ2=5.330, 6.498, 4.574, P<0.05). The results of multivariate analysis showed that male and preoperative adephagia habit were independent risk factors affecting 30-day readmission after bariatric and metabolic surgery (OR=2.489, 2.912, 95% confidence interval: 1.006-6.161, 1.196-7.088, P<0.05). Conclusions Nausea, vomiting and dehydration are common manifestations of patients with 30-day readmission after bariatric and metabolic surgery, and it might be associated with improper food intake. Male and preoperative adephagia habit are independent risk factors affecting 30-day readmission after bariatric and metabolic surgery. Key words: Obesity; Bariatric surgery; Metabolic surgery; Complications; Readmission

Evidence suggests that bariatric surgery alters gut microbiota, although its impact at compositional and functional level is not well described. In this review, the most relevant findings, mainly described in Roux-en-Y gastric bypass and sleeve gastrectomy, are outlined. Although the number of studies has increased in the last years, conclusive assertions cannot be elaborated. An issue to address is to know the influence of these alterations on host metabolism and the contribution of gut microbiota derived metabolites. New lines of research have been focusing on analysing gut microbiota functionality rather than evaluating changes at compositional level, and the functions of gut microbiota metabolites in host metabolism, what will bring more relevant information about the influence of gut microbiota in bariatric surgery outcomes. Personalized medicine, because of the predictive value of gut microbiota, is another promising field. The possibility of a specific gut microbiota pattern that could predict type 2 diabetes remission or weight loss failure after bariatric surgery is a matter of great interest. However, little is known about how gut microbiota manipulation could contribute to the beneficial effects of bariatric surgery. Peri-operative antibiotics prophylaxis or probiotic supplementation early after surgery, are strategies barely studied so far, and could constitute a novel tool in the management of weight loss and metabolic profile improvement after surgery.

BackgroundCurrent evidence support that the gut microbiota plays a potential role in obesity. Bariatric surgery can reduce excess weight and decrease the risk of life-threatening weight-related health problems and may also influence gut microbiota. In this study, we aimed to investigate the changes in gut microbiota before and after bariatric surgery and evaluate the association of the gut microbial shift and altered body mass index (BMI) after bariatric surgery.MethodsBetween January 2019 and July 2020, stools from 58 patients scheduled for bariatric surgery were collected. Six months after bariatric surgery, stools from 22 of these patients were re-collected, and the changes in gut microbiota before and after bariatric surgery were evaluated. In addition, the differences in gut microbiota between patients with severe obesity (BMI >35 kg/m2, n=42) and healthy volunteers with normal BMI (18.8 to 22.8 kg/m2, n=41) were investigated.ResultsThe gut microbiota of patients who underwent bariatric surgery showed increased α-diversity and differed β-diversity compared with those before surgery. Interestingly, Blautia was decreased and Bacteriodes was increased at the genus level after bariatric surgery. Further, the Blautia/Bacteroides ratio showed a positive correlation with BMI. To validate these results, we compared the gut microbiota from severely obese patients with high BMI with those from healthy volunteers and demonstrated that the Blautia/Bacteroides ratio correlated positively with BMI.ConclusionIn the gut microbial analysis of patients who underwent bariatric surgery, we presented that the Blautia/Bacteroides ratio had changed after bariatric surgery and showed a positive correlation with BMI.

5-Fluorouracil (5-FU), irinotecan (CPT-11), oxaliplatin (L-OHP), and calcium folinate (CF) are widely used chemotherapeutic drugs to treat colorectal cancer. However, chemotherapeutic use is often accompanied by intestinal inflammation and gut microbiota disorder. Changes in gut microbiota may destroy the intestinal barrier, which contributes to the severity of intestinal injury. However, intestinal injury and gut microbiota disorder have yet to be compared among 5-FU, CPT-11, L-OHP, and CF in detail, thereby limiting the development of targeted detoxification therapy after chemotherapy. In this study, a model of chemotherapy-induced intestinal injury in tumor-bearing mice was established by intraperitoneally injecting chemotherapeutic drugs at a clinically equivalent dose. 16S rRNA gene sequencing was used to detect gut microbiota. We found that 5-FU, CPT-11, and l-OHP caused intestinal injury, inflammatory cytokine (gamma interferon [IFN-γ], tumor necrosis factor alpha [TNF-α], interleukin-1β [IL-1β], and IL-6) secretion, and gut microbiota disorder. We established a complex but clear network between the pattern of changes in gut microbiota and degree of intestinal damage induced by different chemotherapeutic drugs. L-OHP caused the most severe damage in the intestine and disorder of the gut microbiota and showed a considerable overlap of the pattern of changes in microbiota with 5-FU and CPT-11. Analysis by Phylogenetic Investigation of Communities by Reconstruction of Unobserved States (PICRUSt v.1.0) showed that the microbiota disorder pattern induced by 5-FU, CPT-11, and L-OHP was related to the NOD-like signaling pathway. Therefore, we detected the protein expression of the NOD/RIP2/NF-κB signaling pathway and found that L-OHP most activated this pathway. Redundancy analysis/canonical correlation analysis (RDA/CCA) revealed that Bifidobacterium, Akkermansia, Allobaculum, Catenibacterium, Mucispirillum, Turicibacter, Helicobacter, Proteus, Escherichia Shigella, Alloprevotealla, Vagococcus, Streptococcus, and "Candidatus Saccharimonas" were highly correlated with the NOD/RIP2/NF-κB signaling pathway and influenced by chemotherapeutic drugs. IMPORTANCE Chemotherapy-induced intestinal injury limits the clinical use of drugs. Intestinal injury involves multiple signaling pathways and gut microbiota disruption. Our results suggested that the degree of intestinal injury caused by different drugs of the first-line colorectal chemotherapy regimen is related to the pattern of changes in microbiota. The activation of the NOD/RIP2/NF-κB signaling pathway was also related to the pattern of changes in microbiota. l-OHP caused the most severe damage to the intestine and showed a considerable overlap of the pattern of changes in microbiota with 5-FU and CPT-11. Thirteen bacterial genera were related to different levels of intestinal injury and correlated with the NOD/RIP2/NF-κB pathway. Here, we established a network of different chemotherapeutic drugs, gut microbiota, and the NOD/RIP2/NF-κB signaling pathway. This study likely provided a new basis for further elucidating the mechanism and clinical treatment of intestinal injury caused by chemotherapy.

Improvements in estrogen deficiency-induced hypercholesterolemia by Hypericum perforatum L. extract are associated with gut microbiota and related metabolites in ovariectomized (OVX) rats

TFRD has been widely used in China to treat osteoporosis (OP). However, the specific molecular mechanism of TFRD against OP has not been fully clarified. Our previous studies have also proved that TFRD could attenuate OP and the clinical equivalent dose of 67.5mg/kg/d is the effective dose for TFRD treating OP. Therefore, this study used 67.5mg/kg as the dosage of TFRD in combination with multi omics to investigate the mechanism of action of TFRD in the treatment of OP. The aim of this study was to further elucidate molecular mechanism of TFRD for treating OP based on metagenomic and metabolomic analyses. In this study, hematoxylin-eosin (H&E) staining, micro computed tomography (micro-CT) and bone mineral density (BMD) analysis were used to observe pharmacological effects of TFRD against ovariectomized (OVX)-induced OP. Subsequently, multiomics analysis including metagenomics, untargeted and short chain fatty acids (SCFAs) metabolomics were carried out to identify whether the anti-osteoporosis mechanism of TFRD correlated with gut microbiota and related metabolites. Our results indicate that TFRD could improve the microstructure and density of trabecular bone in OVX rats. 17 differential species, which mainly from Akkermansia, Bacteroides, and Phascolarctobacterium genus, 14 related differential metabolites and acetic acid in SCFAs were significantly altered by OVX and reversed by TFRD. Furthermore, according to results of untargeted metabolomics analysis, it was found that several metabolic pathways such as phenylalanine metabolism, phenylalanine, tyrosine and tryptophan biosynthesis and so on might play an important role in TFRD against OP. In order to further study the relationship between gut microbiota and related metabolites, spearman correlation analysis was used, and showed that gut microbiota such as Akkermansia muciniphila might be closely related to several metabolites and metabolic pathways. These findings suggest that TFRD treatment could reduce the effects of OVX-induced OP by altering community composition and abundance of gut microbiota, regulating metabolites and SCFAs. It was speculated that the gut microbiota especially Akkermansia muciniphila and related metabolites might play an important role in TFRD against OP, and deserve further study by follow-up experiment. This conclusion provides new theoretical support for mechanism research of TFRD against OP.

Background: Although associations between low protein diet (LPD) and changes of gut microbiota have been reported; however, systematic discernment of the effects of LPD on diet-microbiome-host interaction in patients with chronic kidney disease (CKD) is lacking.Methods: We searched PUBMED and EMBASE for articles published on changes of gut microbiota associated with implementation of LPD in CKD patients until July 2021. Independent researchers extracted data and assessed risks of bias. We conducted meta-analyses of combine p-value, mean differences and random effects for gut microbiota and related metabolites. Study heterogeneity was measured by Tau2 and I2 statistic. This study followed the Preferred Reporting Items for Systematic Reviews and Meta-Analyses guidelines.Results: Five articles met inclusion criteria. The meta-analyses of gut microbiota exhibited enrichments of Lactobacillaceae (meta-p= 0.010), Bacteroidaceae (meta-p= 0.048) and Streptococcus anginosus (meta-p< 0.001), but revealed depletion of Bacteroides eggerthii (p=0.017) and Roseburia faecis (meta-p=0.019) in LPD patients compared to patients undergoing normal protein diet. The serum IS levels (mean difference: 0.68 ug/mL, 95% CI: -8.38-9.68, p= 0.89) and pCS levels (mean difference: -3.85 ug/mL, 95% CI: -15.49-7.78, p < 0.52) did not change between groups. We did not find significant differences on renal function associated with change of microbiota between groups (eGFR, mean difference: -7.21 mL/min/1.73 m2, 95% CI: -33.2-18.79, p= 0.59; blood urea nitrogen, mean difference: -6.8 mg/dL, 95% CI: -46.42-32.82, p= 0.74). Other clinical (sodium, potassium, phosphate, albumin, fasting sugar, uric acid, total cholesterol, triglycerides, C-reactive protein and hemoglobin) and anthropometric estimates (body mass index, systolic blood pressure and diastolic blood pressure) did not differ between the two groups.Conclusions: This systematic review and meta-analysis suggested that the effects of LPD on the microbiota were observed predominantly at the families and species levels but minimal on microbial diversity or richness. In the absence of global compositional microbiota shifts, the species-level changes appear insufficient to alter metabolic or clinical outputs.