The gut microbiome is altered after bariatric surgery and is associated with weight loss. However, the commensal bacteria involved and the underlying mechanism remain to be determined. We performed shotgun metagenomic sequencing in obese subjects before and longitudinally after sleeve gastrectomy (SG), and found a significant enrichment in microbial species in Clostridia and bile acid metabolizing genes after SG treatment. Bile acid profiling further revealed decreased primary bile acids (PBAs) and increased conjugated secondary bile acids (C-SBAs) after SG. Specifically, glycodeoxycholic acid (GDCA) and taurodeoxycholic acid (TDCA) were increased at different follow-ups after SG, and were associated with the increased abundance of Clostridia and body weight reduction. Fecal microbiome transplantation with post-SG feces increased SBA levels, and alleviated body weight gain in the recipient mice. Furthermore, both Clostridia-enriched spore-forming bacteria and GDCA supplementation increased the expression of genes responsible for lipolysis and fatty acid oxidation in adipose tissue and reduced adiposity via Takeda G-protein-coupled receptor 5 (TGR5) signaling. Our findings reveal post-SG gut microbiome and C-SBAs as contributory to SG-induced weight loss, in part via TGR5 signaling, and suggest SBA-producing gut microbes as a potential therapeutic target for obesity intervention.

This review discusses findings related to neurological disorders, gut microbiota, and bariatric surgery, focusing on neurotransmitters, neuroendocrine, the pathophysiology of bacteria contributing to disorders, and possible therapeutic interventions. Research on neurotransmitters suggests that their levels are heavily influenced by gut microbiota, which may link them to neurological disorders such as Alzheimer's disease, Parkinson's disease, Multiple sclerosis, Depression, and Autism spectrum disorder. The pathophysiology of bacteria that reach and influence the central nervous system has been documented. Trends in microbiota are often observed in specific neurological disorders, with a prominence of pro-inflammatory bacteria and a reduction in anti-inflammatory types. Furthermore, bariatric surgery has been shown to alter microbiota profiles similar to those observed in neurological disorders. Therapeutic interventions, including fecal microbiota transplants and probiotics, have shown potential to alleviate neurological symptoms. We suggest a framework for future studies that integrates knowledge from diverse research areas, employs rigorous methodologies, and includes long-trial clinical control groups.

Background and Objectives: Type 2 diabetes (T2D), closely associated with obesity, contributes to increased morbidity and mortality due to complications such as cardiometabolic disease. This review aims to evaluate the effectiveness of metabolic and bariatric surgeries (MBS) and endoscopic bariatric therapies (EBTs) in achieving diabetes remission and to examine key predictors influencing remission outcomes. Materials and Methods: This review synthesizes data from studies on MBS and EBT outcomes, focusing on predictors for diabetes remission such as preoperative insulin use, diabetes duration, HbA1c, and C-peptide levels. Additionally, predictive scoring systems, including the Individualized Metabolic Surgery (IMS), DiaRem, Advanced-DiaRem, ABCD, and Robert et al. scores, were analyzed for their utility in forecasting remission likelihood. Results: Key predictors of T2D remission include shorter diabetes duration, lower HbA1c, and higher C-peptide levels, while prolonged insulin use, and higher insulin doses are associated with lower remission rates. Scoring models like IMS and DiaRem demonstrate that lower scores correlate with a higher likelihood of remission, especially for procedures such as Roux-En-Y gastric bypass (RYGB). RYGB generally shows higher remission rates compared to sleeve gastrectomy (SG), particularly among patients with mild disease severity, while EBTs like ESG and IGBs contribute 5-20% total weight loss (TWL) and moderate glycemic control improvements. Conclusions: Both MBS and EBTs are effective for T2D management, with predictive scoring models aiding in individualized patient selection to optimize remission outcomes. Further research to validate these predictive tools across diverse populations could enhance treatment planning for both surgical and endoscopic interventions.

Carbohydrates, lipids, bile acids, various inorganic salt ions and organic acids are the main nutrients or indispensable components of the human body. Dysregulation in the processes of absorption, transport, metabolism, and excretion of these metabolites can lead to the onset of severe metabolic disorders, such as type 2 diabetes, non-alcoholic fatty liver disease, gout and hyperbilirubinemia. As the second largest membrane receptor supergroup, several major families in the solute carrier (SLC) supergroup have been found to play key roles in the transport of substances such as carbohydrates, lipids, urate, bile acids, monocarboxylates and zinc ions. Based on common metabolic dysregulation and related metabolic substances, we explored the relationship between several major families of SLC supergroup and metabolic diseases, providing examples of drugs targeting SLC proteins that have been approved or are currently in clinical/preclinical research as well as SLC-related diagnostic techniques that are in clinical use or under investigation. By highlighting these connections, we aim to provide insights that may contribute to the development of improved treatment strategies and targeted therapies for metabolic disorders.

Advances in treatment strategies for gastric and esophageal cancer have led to improved long-term outcomes, however the local and systemic effects of the primary tumor, neoadjuvant therapies and surgery, result in specific nutritional challenges. Comprehensive nutritional evaluation and support represents a core component of multidisciplinary holistic care for this patient population.

We provide a detailed overview of nutritional challenges in gastric and esophageal cancer, with a focus on malignant obstruction, preoperative optimization and survivorship. We discuss current management strategies and evidence base, and describe future therapeutic targets.

Data to support the optimal management of malignant dysphagia and obstruction, particularly regarding patient reported outcomes, is currently lacking. The advantages of nutritional optimization in the pre- and immediate postoperative phase are well described, but further research is needed to inform optimal personalised strategies. Emerging data regarding the physiologic regulation of appetite and body weight have provided key insights and informed the development of novel therapeutic targets to improve nutritional status among patients undergoing treatment for oesophageal and gastric cancer.

Unexplainable gastrointestinal complaints occasionally occur after Roux-en-Y Gastric Bypass (RYGB) surgery. We therefor investigated the impact of microbiota composition and metabolites on gastrointestinal complaints after RYGB. In the BARICO study (Bariatric surgery Rijnstate and Radboudumc neuroimaging and Cognition in Obesity), microbiota and metabolites were measured before surgery, and 6, and 24 months after surgery. Gastrointestinal complaints were assessed with the Irritable Bowel Syndrome Severity Scoring System (IBS-SSS) questionnaire 24 months after surgery. 65 participants (86.2 % female) with a mean age of 46.2 ± 6.0 years, and mean BMI of 41.2 ± 3.6 kg/m2 were included. According to the IBS-SSS questionnaire, 32.3 % had moderate/severe gastrointestinal complaints 24 months after surgery. Microbiota alpha diversity remained stable, while beta diversity significantly changed over time. Bile acids and short-chain fatty acids were significantly higher, and inflammatory markers significantly lower after surgery. Barnesiella sp., Escherichia/Shigella sp., and Faecalibacterium prausnitzii correlated positively, while Akkermansia sp correlated inversely with gastrointestinal complaints. Patients with mild and moderate/severe gastrointestinal complaints showed higher levels of GLC-3S. These findings suggest involvement of microbiota and metabolite changes in gastrointestinal complaints after surgery. However, it remains unclear whether bacteria influence gastrointestinal complaints directly or indirectly. Further exploration is required for development of interventions against gastrointestinal symptoms after surgery.

The objective of this study was to assess maternal gestational outcomes and offspring growth trajectories following prepregnancy metabolic and bariatric surgery (MBS) compared with non-MBS controls.

Single-center deliveries between January 2020 and March 2023 with prepregnancy Roux-en-Y gastric bypass (herein referred to as "bypass"), sleeve gastrectomy (herein referred to as "sleeve"), and non-MBS controls were included. Offspring growth trajectories were compared with the World Health Organization child growth standards. Linear mixed models assessed MBS-bypass and MBS-sleeve offspring weight, length, and BMI trajectories with a prepregnancy BMI 27 to 37 kg/m2 and propensity score-matched controls.

The study included 440 participants with prepregnancy MBS (MBS-bypass, 185; MBS-sleeve, 225; 76% Hispanic/Latino) and 13,434 non-MBS controls. Gestational weight gain and gestational diabetes mellitus were similar, whereas hypertensive disorders of pregnancy were more common after MBS. The post-MBS offspring had lower birth weight but higher weight gain at 24 months (sleeve, +1.4 kg [95% CI: 1.0-1.9]; bypass, +0.5-0.7 kg [95% CI: 0.0-1.2]) compared with non-MBS groups. Male children had higher weight gain than females. The post-MBS-sleeve but not the post-MBS-bypass offspring had higher BMI z scores.

The higher early-life weight gain and sex differences in the post-MBS-sleeve group compared with the post-MBS-bypass group provide a window toward elucidating pathways to mitigate intergenerational metabolic risk transfer.

Bile acids (BA) are supposed to cause metabolic alterations after bariatric surgery (BS). Here we report the longitudinal dynamics of the human BA metabolome by LC-MS/MS after BS versus low calory diet (LCD) in two obesity cohorts over 12 months. Rapid and persistent oscillations of 23 BA subspecies could be identified with highly specific patterns in BS vs. LCD. TCDCA, GLCA, and TLCA represent most promising candidates for drug development.

Excess body fat elevates colorectal cancer risk. While bariatric surgery (BRS) induces significant weight loss, its effects on the fecal stream and colon biology are poorly understood. Specifically, limited data exist on the impact of bariatric surgery (BRS) on fecal secondary bile acids (BA), including lithocholic acid (LCA), a putative promotor of colorectal carcinogenesis.

This cross-sectional case-control study included 44 patients with obesity; 15 pre-BRS (controls) vs. 29 at a median of 24.1 months post-BRS. We examined the fecal concentrations of 11 BA by liquid chromatography and gene abundance of BA-metabolizing bacterial enzymes through fecal metagenomic sequencing. Differences were quantified using non-parametric tests for BA levels and linear discriminant analysis (LDA) effect size (LEfSe) for genes encoding BA-metabolizing enzymes.

Total fecal secondary BA concentrations trended towards lower levels post- vs. pre-BRS controls (p = 0.07). Individually, fecal LCA concentrations were significantly lower post- vs. pre-BRS (8477.0 vs. 11,914.0 uM/mg, p < 0.008). Consistent with this finding, fecal bacterial genes encoding BA-metabolizing enzymes, specifically 3-betahydroxycholanate-3-dehydrogenase (EC 1.1.1.391) and 3-alpha-hydroxycholanate dehydrogenase (EC 1.1.1.52), were also lower post- vs. pre-BRS controls (LDA of - 3.32 and - 2.64, respectively, adjusted p < 0.0001). Post-BRS fecal BA concentrations showed significant inverse correlations with weight loss, a healthy diet quality, and increased physical activity.

Concentrations of LCA, a secondary BA, and bacterial genes needed for BA metabolism are lower post-BRS. These changes can impact health and modulate the colorectal cancer cascade. Further research is warranted to examine how surgical alterations and the associated dietary changes impact bile acid metabolism.

Bile acids are synthesised in the liver and are essential amphiphilic steroids for maintaining the balance of cholesterol and energy metabolism in livestock and poultry. They can be used as novel feed additives to promote fat utilisation in the diet and the absorption of fat-soluble substances in the feed to improve livestock performance and enhance carcass quality. With the development of understanding of intestinal health, the balance of bile acid metabolism is closely related to the composition and growth of livestock intestinal microbiota, inflammatory response, and metabolic diseases. This paper systematically reviews the effects of bile acid metabolism on gut health and gut microbiology in livestock. In addition, our paper summarised the role of bile acid metabolism in performance and disease control.

In recent years, there has been a gradual increase in the prevalence of obesity and type 2 diabetes mellitus (T2DM), with bariatric surgery remaining the most effective treatment strategy for these conditions. Vertical sleeve gastrectomy (VSG) has emerged as the most popular surgical procedure for bariatric/metabolic surgeries, effectively promoting weight loss and improving or curing T2DM. The alterations in the gastrointestinal tract following VSG may improve insulin secretion and resistance by increasing incretin secretion (especially GLP-1), modifying the gut microbiota composition, and through mechanisms dependent on weight loss. This review focuses on the potential mechanisms through which the enhanced action of incretin and metabolic changes in the digestive system after VSG may contribute to the remission of T2DM.

Bariatric surgery is an effective treatment option for obesity and provides long-term weight loss and positive effects on metabolism, but the underlying mechanisms are poorly understood. Alterations in bile acid metabolism have been suggested as a potential contributing factor, but comprehensive studies in humans are lacking.

In this study, we analysed the postprandial responses of bile acids, C4 and FGF19 in plasma, and excretion of bile acids in faeces, before and after bariatric surgery in patients (n = 38; 74% females) with obesity with or without type 2 diabetes from the BARIA cohort.

We observed that total fasting plasma bile acid levels increased, and faecal excretion of bile acids decreased after surgery suggesting increased reabsorption of bile acids. Consistent with increased bile acid levels after surgery we observed increased postprandial levels of FGF19 and suppression of the bile acid synthesis marker C4, suggesting increased FXR activation in the gut. We also noted that a subset of bile acids had altered postprandial responses before and after surgery. Finally, fasting plasma levels of 6α-hydroxylated bile acids, which are TGR5 agonists and associated with improved glucose metabolism, were increased after surgery and one of them, HDCA, covaried with diabetes remission in an independent cohort.

Our findings provide new insights regarding bile acid kinetics and suggest that bariatric surgery in humans alters bile acid profiles leading to activation of FXR and TGR5, which may contribute to weight loss, improvements in glucose metabolism, and diabetes remission.

Novo Nordisk Fonden, Leducq Foundation, Swedish Heart-Lung Foundation, Knut and Alice Wallenberg Foundation, the ALF-agreement, ZonMw.

Changes in microRNAs (miRNAs) are relevant to bariatric surgery and its comorbidities. The characteristics of changes in miRNAs of the early postoperative period following both bariatric procedures, sleeve gastrectomy (SG) and Roux-en-Y gastric bypass (RYGB), as well as the factors that related to the effectiveness of early weight loss remain unclear.

We recruited 18 patients who performed SG and 15 patients who performed RYGB. Their preoperative and 1-month postoperative clinical data and fasting serum samples were collected, and the latter were analyzed by RNA-sequencing. Differential expression analysis of miRNAs was performed by the R-tool. Functional classification annotation and pathway enrichment analysis of targeted genes were analyzed by KOBAS software. The change profiles of miRNAs for both surgeries and their correlation with clinical characteristics and weight loss effectiveness were further analyzed.

A total of 85 differentially expressed miRNAs were identified before and after SG, while a total of 76 were found before and after RYGB. The target genes of these miRNAs were similar in the Gene Ontology enrichment analysis in SG and RYGB, and the enrichment analysis in the Kyoto Encyclopedia of Genes and Genomes was mainly related to metabolic pathways. Hsa-miR-493-5p, hsa-miR-184, and hsa-miR-3199 exhibited similar changes in SG and RYGB, and the former two were correlated with clinical characteristics. Hsa-miR-6729-5p, hsa-miR-4659b-5p, and hsa-miR-2277-5p were correlated with the weight loss effectiveness of SG, while hsa-miR-4662a-5p was correlated with the weight loss effectiveness of RYGB.

Short-term metabolic improvement and weight loss occurring after SG and RYGB surgery might be related to changes in miRNAs, which act on multiple biological pathways by regulating genes. In addition, some clinical characteristics and miRNAs were related to the effectiveness of early weight loss after SG and RYGB surgery.

ChiCTR2200058333.

Bariatric surgery alters bile acid metabolism, which contributes to post-operative improvements in metabolic health. However, the mechanisms by which bariatric surgery alters bile acid metabolism are incompletely defined. In particular, the role of the gut microbiome in the effects of bariatric surgery on bile acid metabolism is incompletely understood. Therefore, we sought to define the changes in gut luminal bile acid composition after vertical sleeve gastrectomy (VSG).

Bile acid profile was determined by UPLC-MS/MS in serum and gut luminal samples from VSG and sham-operated mice. Sham-operated mice were divided into two groups: one was fed ad libitum, while the other was food-restricted to match their body weight to the VSG-operated mice.

VSG decreased gut luminal secondary bile acids, which was driven by a decrease in gut luminal deoxycholic acid concentrations and abundance. However, gut luminal cholic acid (precursor for deoxycholic acid) concentration and abundance did not differ between groups. Therefore, the observed decrease in gut luminal deoxycholic acid abundance after VSG was not due to a reduction in substrate availability.

VSG decreased gut luminal deoxycholic acid abundance independently of body weight, which may be driven by a decrease in gut bacterial bile acid metabolism.

Tripterygium wilfordii polyglycosides (TWP) tablet is the most widely used traditional Chinese medicine preparation for the treatment of rheumatoid arthritis (RA), but the hepatotoxicity often limits its widespread application. In traditional use, Salvia miltiorrhiza has cardioprotective and hepatoprotective effects. Salvianolic acid extract (SA) is a hydrophilic component of Salvia miltiorrhiza and has significant antioxidant and hepatoprotective effects.

To investigate the protective effects of SA on the TWP-induced acute liver injury in rats and to explore the related mechanisms by integration of metabolomics and transcriptomics.

SA and TWP extracts were identified by UPLC-Q/TOF-MS. SA (200 mg/kg) was administered for consecutive 7 days. On day 7, TWP (360 mg/kg) was administered by gavage to induce the acute liver injury in rats. Serum biochemical assay and H&E staining were used to evaluate liver damage. Liver metabolomics and transcriptomics were used to explore the potential mechanisms, and further molecular biological experiments such as qPCR and IHC were utilized to validate the relevant signaling pathways.

SA can prevent liver injury symptoms caused by TWP, such as elevated liver index, elevated ALT and AST, and pathological changes in liver tissue. Liver metabolomics studies showed that TWP can significantly alter the content of individual bile acid in the liver and SA had the most significant impact on the biosynthetic pathway of bile acids. The transcriptomics results of the liver indicated that the genes changed in the SA + TWP group were mainly involved in sterol metabolism, lipid regulation and bile acid homeostasis pathways. The gene expression of Nr1h4, which encodes farnesoid X receptor (FXR), an important regulator of bile acid homeostasis, was significantly changed. Further studies confirmed that SA can prevent the downregulation of FXR and its downstream signaling induced by TWP, thereby regulating bile acid metabolism, ultimately preventing acute liver injury caused by TWP.

Our results demonstrated that SA could protect the liver from TWP-induced hepatic injury by modulation of the bile acid metabolic pathway. SA may provide a new strategy for the protection against TWP-induced acute liver injury.

Obesity remains a significant global health challenge, with bariatric surgery remaining as one of the most effective treatments for severe obesity and its related comorbidities. This review highlights the multifaceted impact of bariatric surgery beyond mere physical restriction or nutrient malabsorption, underscoring the importance of the gut microbiome and neurohormonal signals in mediating the profound effects on weight loss and behavior modification. The various bariatric surgery procedures, such as Roux-en-Y gastric bypass (RYGB) and sleeve gastrectomy (SG), act through distinct mechanisms to alter the gut microbiome, subsequently impacting metabolic health, energy balance, and food reward behaviors. Emerging evidence has shown that bariatric surgery induces profound changes in the composition of the gut microbiome, notably altering the Firmicutes/Bacteroidetes ratio and enhancing populations of beneficial bacteria such as Akkermansia. These microbiota shifts have far-reaching effects beyond gut health, influencing dopamine-mediated reward pathways in the brain and modulating the secretion and action of key gut hormones including ghrelin, leptin, GLP-1, PYY, and CCK. The resultant changes in dopamine signaling and hormone levels contribute to reduced hedonic eating, enhanced satiety, and improved metabolic outcomes. Further, post-bariatric surgical effects on satiation targets are in part mediated by metabolic byproducts of gut microbiota like short-chain fatty acids (SCFAs) and bile acids, which play a pivotal role in modulating metabolism and energy expenditure and reducing obesity-associated inflammation, as well as influencing food reward pathways, potentially contributing to the regulation of body weight and reduction in hedonic eating behaviors. Overall, a better understanding of these mechanisms opens the door to developing non-surgical interventions that replicate the beneficial effects of bariatric surgery on the gut microbiome, dopamine signaling, and gut hormone regulation, offering new avenues for obesity treatment.

A series of 1,1'-biphenyl-3-carboxamide and furan-phenyl-carboxamide analogs were synthesized using an optimized scheme and confirmed by 1H and 13C nuclear magnetic resonance and high-resolution mass spectrometry techniques. The synthesized peptidomimetics analogs were screened in vitro to understand the inhibitory potential of pancreatic lipase (PL). Analogs were assessed for the PL inhibitory activity based on interactions, geometric complementarity, and docking score. Among the synthesized analogs, 9, 29, and 24 were found to have the most potent PL inhibitory activity with IC50 values of 3.87, 4.95, and 5.34 µM, respectively, compared to that of the standard drug, that is, orlistat, which inhibits PL with an IC50 value of 0.99 µM. The most potent analog, 9, exhibited a competitive-type inhibition with an inhibition constant (Ki) of 2.72 µM. In silico molecular docking of analog 9 with the PL (PDB ID:1LPB) showed a docking score of -11.00 kcal/mol. Analog 9 formed crucial hydrogen bond interaction with Ser152, His263, π-cation interaction with Asp79, Arg256, and π-π stacking with Phe77, Tyr114 at the protein's active site. The molecular dynamic simulation confirmed that analog 9 forms stable interactions with PL at the end of 200 ns with root mean square deviation values of 2.5 and 6 Å. No toxicity was observed for analog 9 (concentration range of 1-20 µM) when tested by MTT assay in RAW 264.7 cells.

Polycystic ovary syndrome (PCOS) is the most common endocrine condition in premenopausal women and is a common cause of anovulatory subfertility. Although obesity does not form part of the diagnostic criteria, it affects a significant proportion of women with PCOS and is strongly implicated in the pathophysiology of the disease. Both PCOS and obesity are known to impact fertility in women; obesity also reduces the success of assisted reproductive technology (ART). With or without pharmacotherapy, lifestyle intervention remains the first-line treatment in women with PCOS and obesity. Bariatric surgery is still an experimental treatment in women with PCOS and subfertility. This review will present an overview of the pathophysiology of PCOS and obesity and the role of bariatric surgery. Although data are sparse regarding the impact of bariatric surgery on subfertility in women with PCOS and obesity, existing studies point to a beneficial role in treating metabolic and reproductive dysfunction.

The global prevalence of inflammatory bowel disease (IBD) has steadily risen over the past few decades. Bariatric surgery stands out as an effective strategy for inducing weight loss. This study investigated the impacts of bariatric surgery on the clinical outcomes in patients with IBD.

Data of hospitalized patients aged ≥ 18 years with IBD were extracted from the Nationwide Inpatient Sample (NIS) 2005-2018. The patients were categorized according to whether they underwent bariatric surgery or not. Univariate and multivariable logistic regression analyses were performed to determine the associations between bariatric surgery, prolonged LOS, unfavorable discharge, hospital mortality, and morbidity.

Data from 807,843 hospitalized patients with IBD were extracted. After exclusions and propensity-score matching, 80,545 patients were analyzed, with 16,109 undergoing bariatric surgery and 64,436 not. A total of 23% of patients had a prolonged LOS, 8% had unfavorable discharge, and the mortality rate was 1.2%. Multivariable analyses revealed that, compared to patients without bariatric surgery, patients with bariatric surgery had significantly decreased odds of prolonged LOS (adjusted odds ratio [aOR], 0.89; 95% CI 0.85-0.93), unfavorable discharge (aOR, 0.83; 95% CI: 0.77-0.89), and mortality (aOR, 0.54; 95% CI: 0.44-0.67), but had increased odds of morbidity (aOR, 1.09; 95% CI 1.04-1.13).

In adults with IBD, bariatric surgery is associated with favorable outcomes concerning hospital LOS, discharge status, and mortality. However, the risk of overall morbidity is slightly increased in those who received bariatric surgery compared to those who did not.

Bile acids, which are steroid molecules originating from cholesterol and synthesized in the liver, play a pivotal role in regulating glucose metabolism and maintaining energy balance. Upon release into the intestine alongside bile, they activate various nuclear and membrane receptors, influencing crucial processes. These bile acids have emerged as significant contributors to managing type 2 diabetes mellitus, a complex clinical syndrome primarily driven by insulin resistance. Bile acids substantially lower blood glucose levels through multiple pathways: BA-FXR-SHP, BA-FXR-FGFR15/19, BA-TGR5-GLP-1, and BA-TGR5-cAMP. They also impact blood glucose regulation by influencing intestinal flora, endoplasmic reticulum stress, and bitter taste receptors. Collectively, these regulatory mechanisms enhance insulin sensitivity, stimulate insulin secretion, and boost energy expenditure. This review aims to comprehensively explore the interplay between bile acid metabolism and T2DM, focusing on primary regulatory pathways. By examining the latest advancements in our understanding of these interactions, we aim to illuminate potential therapeutic strategies and identify areas for future research. Additionally, this review critically assesses current research limitations to contribute to the effective management of T2DM.

The effects of bile acids (BAs) on liver, enteroendocrine function, small intestine, and brown adipose tissue have been described extensively. Outside the liver, BAs in the peripheral circulation system represent a specific but underappreciated physiological compartment. We discuss how systemic BAs can be regarded as specific steroidal hormones that act on white adipocytes, and suggest the name 'bilokines' ('bile hormones') for the specific FXR/TGR5 receptor interaction in adipocytes. Some BAs and their agonists regulate adipocyte differentiation, lipid accumulation, hypoxia, autophagy, adipokine and cytokine secretion, insulin signaling, and glucose uptake. BA signaling could provide a new therapeutic avenue for adipoflammation and metaflammation in visceral obesity, the causal mechanisms underlying insulin resistance and type 2 diabetes mellitus (T2D).

The association between bariatric surgery and IBD-related inpatient outcomes is not well characterized. We report, analyze, and compare inpatient trends and outcomes among encounters with a history of bariatric surgery (Hx-MBS) compared to those receiving bariatric surgery during index admission (PR-MBS) admitted from 2009 to 2020.

Retrospective cohort design: the 2009-2020 National Inpatient Sample (NIS) databases were used to identify hospital encounters with patients aged ≥ 18 years with a history of MBS (Hx-MBS) or with procedure coding indicating MBS procedure (PR-MBS) according to International Classification of Diseases, Ninth (ICD-9-CM/ ICD-9-PCS) or Tenth Revision (ICD-10-CM/ICD-10-PCS) Clinical Modification/Procedure Coding System during index admission (ICD-9-CM: V4586; ICD-10-CM: Z9884; ICD-9-PR: 4382, 4389; ICD-10-PR: 0DB64Z3, 0DB63ZZ). Pearson χ2 analysis, analysis of variance, multivariable regression analyses, and propensity matching on independent variables were conducted to analyze significant associations between variables and for primary outcome inflammatory bowel disease-related admission, and secondary outcomes: diagnosis of nonalcoholic steatohepatitis, nonalcoholic fatty liver disease, or chronic mesenteric ischemia during admission.

We identified 3,365,784 (76.20%) Hx-MBS hospitalizations and 1,050,900 hospitalizations with PR-MBS (23.80%). Propensity score matching analysis demonstrated significantly higher odds of inflammatory bowel disease, and chronic mesenteric ischemia for Hx-MBS compared to PR-MBS, and significantly lower odds of nonalcoholic steatohepatitis and nonalcoholic fatty liver disease for Hx-MBS compared to PR-MBS.

In our study, Hx-MBS was associated with significantly increased odds of inflammatory bowel disease and other GI pathologies compared to matched controls. The mechanism by which this occurs is unclear. Additional studies are needed to examine these findings.

Prior studies have demonstrated that both dietary components and bariatric surgery modify the gut microbiota's composition. However, there is a scarcity of research that has examined the relationship between post-surgical dietary intake and changes in the gut microbiota. The aim of this study was to assess changes in gut microbiota following bariatric surgery and examine their association with postoperative dietary intake.

The present study involved a sample of 42 adult women who were potential candidates for bariatric surgery, i.e., laparoscopic Roux-en-Y gastric bypass (LRYGB) or sleeve gastrectomy (LSG). The assessment of dietary intake was conducted through the use of three-day food records, both at baseline and six months following the surgical procedure. The gut microbiota was determined through the detection of 16S ribosomal RNA (16S rRNA) gene sequencing.

After six months, a significant increase in abundance of Firmicutes (P = 0.01), Bifidobacterium (P = 0.01), and Ruminococcus (P = 0.04) in the LSG group was found. In contrast to the observed rise in Enterobacteria (P = 0.02) levels in the LRYGB group, no significant changes were detected in the composition of other gut microbiota over the 6-month monitoring period subsequent to LRYGB. The results of our study indicate that there is not a statistically significant relationship between dietary consumption and changes in the composition of the gut microbiota in individuals who have undergone LRYGB and LSG.

Our findings suggest that there may not be a significant correlation between dietary intake following LRYGB and LSG, and the observed alterations in the gut microbiota during a six-month period of observation. Nevertheless, it is important to acknowledge that the sample size utilized in our study was limited, potentially leading to reduced statistical power and the possibility of yielding findings that do not accurately reflect reality.

While bariatric surgery remains the most effective treatment for obesity that allows substantial weight loss with improvement and possibly remission of obesity-associated comorbidities, some postoperative complications may occur. Managing physicians need to be familiar with the common problems to ensure timely and effective management. Of these complications, postoperative hypoglycemia is an increasingly recognized complication of bariatric surgery that remains underreported and underdiagnosed.

This article highlights the importance of identifying hypoglycemia in patients with a history of bariatric surgery, reviews pathophysiology and addresses available nutritional, pharmacological and surgical management options. Systemic evaluation including careful history taking, confirmation of hypoglycemia and biochemical assessment is essential to establish accurate diagnosis. Understanding the weight-dependent and weight-independent mechanisms of improved postoperative glycemic control can provide better insight into the causes of the exaggerated responses that lead to postoperative hypoglycemia.

Management of post-operative hypoglycemia can be challenging and requires a multidisciplinary approach. While dietary modification is the mainstay of treatment for most patients, some patients may benefit from pharmacotherapy (e.g. GLP-1 receptor antagonist); Surgery (e.g. reversal of gastric bypass) is reserved for unresponsive severe cases. Additional research is needed to understand the underlying pathophysiology with a primary aim in optimizing diagnostics and treatment options.

Different metabolic/bariatric surgery approaches vary in their effect on weight loss and glucose levels, although the underlying mechanism is unclear. Studies have demonstrated that the gut microbiota might be an important mechanism of improved metabolism after metabolic/bariatric surgery.

To investigate the relationship between the improvement in metabolic disturbances and the changes in gut microbiota after gastric or intestinal bypass.

We performed sleeve gastrectomy (SG), distal small intestine bypass (DSIB) or sham surgery in nonobese rats with diabetes induced by 60 mg/kg streptozotocin (STZ-DM).

The group comparisons revealed that both SG and DSIB induced a reduction in body weight and significant improvements in glucose and lipid metabolism in the STZ-DM rats. Furthermore, DSIB exhibited a stronger glucose-lowering and lipid-reducing effect on STZ-DM rats than SG. 16S ribosomal RNA gene sequencing revealed the gut abundance of some Lactobacillus spp. increased in both the SG and DSIB groups after surgery. However, the DSIB group exhibited a more pronounced increase in the gut abundance of Lactobacillus spp. compared to the SG group, with more Lactobacillus spp. types increased in the gut.

The gut abundance of Lactobacillus was significantly correlated with the improvement in glycolipid metabolism and the change in serum fibroblast growth factor 21 levels.

Saudi Arabia has one of the highest obesity rates (35.4%) in the world, and bariatric surgery (BS) has emerged as the most effective treatment for obesity and its comorbidities. Despite its effectiveness, it is a known risk factor for cholelithiasis. The aim of this study is to identify the incidence and risk factors that contribute to the development of symptomatic cholelithiasis after different types of bariatric surgery in Saudi Arabia.

This is a cross-sectional study conducted among the Saudi adult population. The sample size was 706 participants who underwent bariatric surgery from all over Saudi Arabia. Data collection was done through a validated online self-reported survey.

Out of 706 participants who fulfilled the inclusion criteria, it was found that the incidence of gallstones (GS) after bariatric surgery was 18.8%. The most incidence was during the first year of surgery, where the number of individuals reached 80.4%. The majority were in females (22.9%) and those who underwent Roux-en-Y gastric bypass (RYGB) surgery (51.2%). Patients who had a body mass index (BMI) of >25 kg/m² significantly had a higher incidence of gallstones (23.1%) compared to those who had a lesser BMI (15.8%). As the analysis showed, the medication used to prevent the occurrence of gallstones can be considered one of the protective factors, where 85.4% of individuals who used these medications did not develop cholelithiasis.

 The incidence of gallstones after bariatric surgery was high, particularly within the first year of surgery. The increase in postoperative gallstone formation is correlated with hyperlipidemia and Roux-en-Y gastric bypass as basic predictive factors. On the contrary, the medication used to prevent the occurrence of gallstones is considered a protective factor.

Current views show that an impaired balance partly explains the fat accumulation leading to obesity. Fetal malnutrition and early exposure to endocrine-disrupting compounds also contribute to obesity and impaired insulin secretion and/or sensitivity. The liver plays a major role in systemic glucose homeostasis through hepatokines secreted by hepatocytes. Hepatokines influence metabolism through autocrine, paracrine, and endocrine signaling and mediate the crosstalk between the liver, non-hepatic target tissues, and the brain. The liver also synthetizes bile acids (BAs) from cholesterol and secretes them into the bile. After food consumption, BAs mediate the digestion and absorption of fat-soluble vitamins and lipids in the duodenum. In recent studies, BAs act not simply as fat emulsifiers but represent endocrine molecules regulating key metabolic pathways. The liver is also the main site of the production of ketone bodies (KBs). In prolonged fasting, the brain utilizes KBs as an alternative to CHO. In the last few years, the ketogenic diet (KD) became a promising dietary intervention. Studies on subjects undergoing KD show that KBs are important mediators of inflammation and oxidative stress. The present review will focus on the role played by hepatokines, BAs, and KBs in obesity, and diabetes prevention and management and analyze the positive effects of BAs, KD, and hepatokine receptor analogs, which might justify their use as new therapeutic approaches for metabolic and aging-related diseases.

Type 2 diabetes (T2D) is a challenging health concern worldwide. A lifestyle intervention to treat T2D is difficult to adhere, and the effectiveness of approved medications such as metformin, thiazolidinediones (TZDs), and sulfonylureas are suboptimal. On the other hand, bariatric procedures such as Roux-en-Y gastric bypass (RYGB) are being recognized for their remarkable ability to achieve diabetes remission, although the underlying mechanism is not clear. Recent evidence points to branched-chain amino acids (BCAAs) as a potential contributor to glucose impairment and insulin resistance. RYGB has been shown to effectively lower plasma BCAAs in insulin-resistant or T2D patients that may help improve glycemic control, but the underlying mechanism for BCAA reduction is not understood. Hence, we attempted to explore the mechanism by which RYGB reduces BCAAs. To this end, we randomized diet-induced obese (DIO) mice into three groups that underwent either sham or RYGB surgery or food restriction to match the weight of RYGB mice. We also included regular chow-diet-fed healthy mice as an additional control group. Here, we show that compared to sham surgery, RYGB in DIO mice markedly lowered serum BCAAs most likely by rescuing BCAA breakdown in both liver and white adipose tissues. Importantly, the restored BCAA metabolism following RYGB was independent of caloric intake. Fasting insulin and HOMA-IR were decreased as expected, and serum valine was strongly associated with insulin resistance. While gut hormones such as glucagon-like peptide-1 (GLP-1) and peptide YY (PYY) are postulated to mediate various surgery-induced metabolic benefits, mice lacking these hormonal signals (GLP-1R/Y2R double KO) were still able to effectively lower plasma BCAAs and improve glucose tolerance, similar to mice with intact GLP-1 and PYY signaling. On the other hand, mice deficient in fibroblast growth factor 21 (FGF21), another candidate hormone implicated in enhanced glucoregulatory action following RYGB, failed to decrease plasma BCAAs and normalize hepatic BCAA degradation following surgery. This is the first study using an animal model to successfully recapitulate the RYGB-led reduction of circulating BCAAs observed in humans. Our findings unmasked a critical role of FGF21 in mediating the rescue of BCAA metabolism following surgery. It would be interesting to explore the possibility of whether RYGB-induced improvement in glucose homeostasis is partly through decreased BCAAs.

After a high-fat and high-sugar diet, the duodenal mucosa of rodents proliferate and trigger the signal of insulin resistance, which may be the cause of type 2 diabetes (T2D). In response to this phenomenon, researchers have designed the duodenal mucosal resurfacing (DMR) procedure, mainly through the hydrothermal ablation procedure, to restore the normal mucosal surface, thereby correcting this abnormal metabolic signal. This article aims to understand the changes in duodenum before and after the onset or treatment of T2D, and the potential mechanisms of DMR procedure.

A literature search of PubMed and Web of Science was conducted using appropriate keywords.

Both animal and clinical studies have shown that the villus thickness, intestinal cells, glucose transporters, enteric nerves, and gut microbiota and their metabolites in the duodenum undergo corresponding changes before and after the onset or treatment of T2D. These changes may be related to the pathogenesis of T2D. DMR procedure may produce beneficial glycemic and hepatic metabolic effects by regulating these changes.

The duodenum is an important metabolic signaling center, and limiting nutrient exposure to this critical region will have powerful metabolic benefits. The DMR procedure may regulate glycemic and hepatic parameters through various mechanisms, which needs to be further confirmed by a large number of animal and clinical studies.

Bile acids (BAs) are amphipathic molecules synthetized in the liver. They are primarily involved in the digestion of nutrients. Apart from their role in dietary lipid absorption, BAs have progressively emerged as key regulators of systemic metabolism and inflammation. In the last decade, it became evident that BAs are particularly important for the regulation of glucose, lipid, and energy metabolism. Indeed, the interest in role of BA in metabolism homeostasis is further increased due to the global public health increase in obesity and related complications and a large number of research postulating that there is a close mutual relationship between BA and metabolic disorders. This strong relationship seems to derive from the role of BAs as signaling molecules involved in the regulation of a wide spectrum of metabolic pathways. These actions are mediated by different receptors, particularly nuclear farnesoid X receptor (FXR) and Takeda G protein coupled receptor 5 (TGR5), which are probably the major effectors of BA actions. These receptors activate transcriptional networks and signaling cascades controlling the expression and activity of genes involved in BA, lipid and carbohydrate metabolism, energy expenditure, and inflammation. The large correlation between BAs and metabolic disorders offers the possibility that modulation of BAs could be used as a therapeutic approach for the treatment of metabolic diseases, including obesity itself. The aim of this review is to describe the main physiological and metabolic actions of BA, focusing on its signaling pathways, which are important in the regulation of metabolism and might provide new BA -based treatments for metabolic diseases.

Gut microbiota (GM) after bariatric surgery (BS) has been considered as a factor associated with metabolic improvements and weight loss. In this systematic review, we evaluate changes in the GM, characterized by 16S rRNA and metagenomics techniques, in obese adults who received BS. The PubMed, Scopus, Web of Science, and LILACS databases were searched. Two independent reviewers analyzed articles published in the last ten years, using Rayyan QCRI. The initial search resulted in 1275 documents, and 18 clinical trials were included after the exclusion criteria were applied. The predominance of intestinal bacteria phyla varied among studies; however, most of them reported a greater amount of Bacteroidetes (B), Proteobacteria (P), and diversity (D) after BS. Firmicutes (F), B, and the (F/B) ratio was inconsistent, increasing or decreasing after Roux-en-Y gastric bypass (RYGB) and sleeve gastrectomy (SG) were conducted, compared to before surgery. There was a reduction in the relative proportion of F. Moreover, a higher proportion of Actinobacteria (A) was observed after RYGB was conducted. However, the same was not identified when SG procedures were applied. Genera abundance and bacteria predominance varied according to the surgical procedure, with limited data regarding the impact on phyla. The present study was approved by PROSPERO, under registration number CRD42020209509.

The gut microbiota is critical to human health, such as digesting nutrients, forming the intestinal epithelial barrier, regulating immune function, producing vitamins and hormones, and producing metabolites to interact with the host. Meanwhile, increasing evidence indicates that the gut microbiota has a strong correlation with the occurrence, progression and treatment of cardiovascular diseases (CVDs). In patients with CVDs and corresponding risk factors, the composition and ratio of gut microbiota have significant differences compared with their healthy counterparts. Therefore, gut microbiota dysbiosis, gut microbiota-generated metabolites, and the related signaling pathway may serve as explanations for some of the mechanisms about the occurrence and development of CVDs. Several studies have also demonstrated that many traditional and latest therapeutic treatments of CVDs are associated with the gut microbiota and its generated metabolites and related signaling pathways. Given that information, we summarized the latest advances in the current research regarding the effect of gut microbiota on health, the main cardiovascular risk factors, and CVDs, highlighted the roles and mechanisms of several metabolites, and introduced corresponding promising treatments for CVDs regarding the gut microbiota. Therefore, this review mainly focuses on exploring the role of gut microbiota related metabolites and their therapeutic potential in CVDs, which may eventually provide better solutions in the development of therapeutic treatment as well as the prevention of CVDs.

Bariatric-metabolic surgery (BMS) in patients with obesity frequently leads to remission of concurrent type 2 diabetes mellitus (T2DM), even before body weight loss takes place. This is probably based on the correction of a dysmetabolic cycle in the gastrointestinal physiology of T2DM that includes increased vagus-dependent exocrine pancreatic secretion (EPS) and, hence, amplified digestion and nutrient absorption. The resultant chronic exposure of tissues to high plasma levels of glucose, fatty acids and amino acids causes tissue resistance to the actions of insulin and, at a later stage, β-cell dysfunction and reduction of insulin release. We hypothesize that the addition of a surgical truncal vagotomy (TV) may improve and solidify the beneficial results of BMS on T2DM by stably decreasing EPS, - hence reducing the digestion and absorption of nutrients -, and increasing incretin secretion as a result of increased delivery of unabsorbed nutrients to the distal intestine. This hypothesis is supported by surgical data from gastrointestinal malignancies and peptic ulcer operations that include TV, as well as by vagal blockade studies. We suggest that TV may result in a stable reduction of EPS, and that its combination with the appropriate type of BΜS, may enhance and sustain the salutary effects of the latter on T2DM.

Bile acids (BAs) have been proposed to promote gastrointestinal cells carcinogenesis. However, studies on serum total bile acid (TBA) levels and gastrointestinal cancers (GICs) risk are rare.

We conducted a retrospective case-control study from 2015 to 2019 at the First Affiliated Hospital of Air Force Military Medical University, in which 4,256 GICs cases and 1,333 controls were recruited. Patients' demographic, clinical and laboratory data were collected. The odds ratios (ORs) with 95% confidence intervals (CIs) were estimated using binary logistic regression models.

Positive associations were observed between serum TBA levels and risks of esophageal cancer (EC), gastric cancer (GC) and colorectal cancer (CRC). Overall, ORs of EC, GC and CRC risk rose with the TBA levels increasing. After adjustment for potential confounders, the OR of TBA-positive for EC risk was 4.89 (95% CI: 3.20-7.49), followed by GC (OR: 3.92, 95% CI: 2.53-6.08), and CRC (OR: 3.32, 95% CI: 2.04-5.11). Patients aged 60 years or older have a higher risk of GICs, especially for EC patients. Males are associated with a higher risk of GC, while females are associated with a higher risk of CRC. Preoperative serum TBA positive and negative was significantly different in the presence or absence of hematogenous metastasis among EC patients (P=0.014), and lymph node metastasis among GC patients (P=0.018).

This retrospective study showed positive associations between serum TBA level and GICs risk, and a higher serum TBA level constitutes a risk factor for GICs.

Bariatric surgery determines a rearrangement of the gastrointestinal tract that influences nutrient handling and plays a role in the metabolic changes observed after surgery. Most of the changes depend on the accelerated gastric emptying observed in Roux-en-Y gastric bypass (RYGB) and, to a lesser extent, in sleeve gastrectomy (SG). The rapid delivery of meal into the jejunum, particularly after RYGB, contributes to the prompt appearance of glucose in peripheral circulation. Glucose increase is the principal determinant of GLP-1 increase with the consequent stimulation of insulin secretion, the latter balanced by a paradoxical glucagon increase that stimulates EGP to prevent hypoglycaemia. Protein digestion and amino acid absorption appear accelerated after RYGB but not after SG. After RYGB, the adaptation of the gut to the new condition participates to the metabolic change. The intestinal transit is delayed, the gut microbioma is changed, the epithelium becomes hypertrophic and increases the expression of glucose transporter and of the number of cell secreting hormones. These changes are not observed after SG. After RYGB-less after SG-bile acids (BA) increase, influencing glucose metabolism probably modulating FXR and TGR5 with an effect on insulin sensitivity. Muscle, hepatic and adipose tissue insulin sensitivity improve, and the gut reinforces the recovery of IS by enhancing glucose uptake and through the effect of the BA. The intestinal changes observed after RYGB result in a light malabsorption of lipid but not of carbohydrate and protein. In conclusion, functional and morphological adaptations of the gut after RYGB and SG activate inter-organs cross-talk that modulates the metabolic changes observed after surgery.Level of evidence Level V, narrative literature review.

Bariatric surgery (BS) is the most effective therapy for severe obesity, which improves several comorbidities (such as diabetes, hypertension, dyslipidemia, among others) and results in marked weight loss. Despite these consensual beneficial effects, sleeve gastrectomy and Roux-en-Y gastric bypass (the two main bariatric techniques) have also been associated with changes in bone metabolism and progressive bone loss. The objective of this literature review is to examine the impact of bariatric surgery on bone and its main metabolic links, and to analyze the latest findings regarding the risk of fracture among patients submitted to bariatric surgery.

Obesity and fast weight loss in the postoperative period of bariatric surgery increase significantly the risk of cholelithiasis. Moreover, emerging evidence has pointed out the role of bile acids as possible metabolism and weight loss enhancers. This study aims to analyze the influence of cholecystectomy (CL) concomitant with bariatric surgery on weight loss, metabolic repercussions, and postoperative morbidity.

Retrospective cohort study. A total of 363 medical records were analyzed between 2002 and 2017, with 255 patients divided into four groups: with concomitant CL: sleeve gastrectomy (SG + CL group) and Roux-en-Y gastric bypass (GB + CL group); without concomitant CL: sleeve gastrectomy (SG group) and RYGB (GB group).

CL concomitant with bariatric surgery is not related to worse long-term metabolic outcomes when compared to isolated bariatric surgery. In the postoperative follow-up of the isolated bariatric surgeries, 18 (16.5%) patients underwent cholecystectomy. There was no statistical difference between the groups regarding post-surgical complications.

CL did not lead to worse metabolic outcomes and was also not related to a higher incidence of postoperative complications. Cholelithiasis and cholecystitis are important concerns in the postoperative period of bariatric surgery and a careful evaluation of the concomitant procedure should be performed.

Obesity surgery remains the most effective treatment for obesity and its complications. Weight loss was initially attributed to decreased energy absorption from the gut but has since been linked to reduced appetitive behavior and potentially increased energy expenditure. Implicated mechanisms associating rearrangement of the gastrointestinal tract with these metabolic outcomes include central appetite control, release of gut peptides, change in microbiota, and bile acids. However, the exact combination and timing of signals remain largely unknown. In this review, we survey recent research investigating these mechanisms, and seek to provide insights on unanswered questions over how weight loss is achieved following bariatric surgery which may eventually lead to safer, nonsurgical weight-loss interventions or combinations of medications with surgery.