Multi-omic phenotyping reveals host-microbe responses to bariatric surgery, glycaemic control and obesity.

Background: Resolution of type 2 diabetes (T2D) is common following bariatric surgery, particularly Roux-en-Y gastric bypass. However, the underlying mechanisms have not been fully elucidated. Methods: To address this we compare the integrated serum, urine and faecal metabolic profiles of participants with obesity ± T2D (n = 80, T2D = 42) with participants who underwent Roux-en-Y gastric bypass or sleeve gastrectomy (pre and 3-months post-surgery; n = 27), taking diet into account. We co-model these data with shotgun metagenomic profiles of the gut microbiota to provide a comprehensive atlas of host-gut microbe responses to bariatric surgery, weight-loss and glycaemic control at the systems level. Results: Here we show that bariatric surgery reverses several disrupted pathways characteristic of T2D. The differential metabolite set representative of bariatric surgery overlaps with both diabetes (19.3% commonality) and body mass index (18.6% commonality). However, the percentage overlap between diabetes and body mass index is minimal (4.0% commonality), consistent with weight-independent mechanisms of T2D resolution. The gut microbiota is more strongly correlated to body mass index than T2D, although we identify some pathways such as amino acid metabolism that correlate with changes to the gut microbiota and which influence glycaemic control. Conclusion: We identify multi-omic signatures associated with responses to surgery, body mass index, and glycaemic control. Improved understanding of gut microbiota - host co-metabolism may lead to novel therapies for weight-loss or diabetes. However, further experiments are required to provide mechanistic insight into the role of the gut microbiota in host metabolism and establish proof of causality.

The impact of bariatric surgery on serum tryptophan-kynurenine pathway metabolites.

This study aims to explore the immediate effects of bariatric surgery on serum tryptophan-kynurenine pathway metabolites in individuals with type 2 diabetes and BMI > 30. With the goal of providing insight into the link between tryptophan pathway metabolites, type 2 diabetes, and chronic obesity-induced inflammation. This longitudinal study included 20 participants. Half were diagnosed with type 2 diabetes. 11 and 9 underwent RYGB and SG respectively. Blood samples were obtained at pre-operative and 3 months post-operative timepoints. Tryptophan and downstream metabolites of the kynurenine pathway were quantified with an ultrahigh-performance liquid chromatography tandem mass spectrometry with electrospray ionisation method. At 3 months post-operation, RYGB led to significant reductions in tryptophan, kynurenic acid and xanthurenic acid levels when compared to baseline. Significant reductions of the same metabolites after surgery were also observed in individuals with T2D irrespective of surgical procedure. These metabolites were significantly correlated with serum HbA1c levels and BMI. Bariatric surgery, in particular RYGB reduces serum levels of tryptophan and its downstream kynurenine metabolites. These metabolites are associated with T2D and thought to be potentially mechanistic in the systemic processes of obesity induced inflammation leading to insulin resistance. Its reduction after surgery is associated with an improvement in glycaemic control (HbA1c).

A Subset of Roux-en-Y Gastric Bypass Bacterial Consortium Colonizes the Gut of Nonsurgical Rats without Inducing Host-Microbe Metabolic Changes.

Roux-en-Y gastric bypass (RYGB) is an effective weight loss surgery, resulting in a characteristic increase of fecal Gammaproteobacteria The contribution of this compositional change to metabolic benefits of RYGB is currently debatable. Therefore, this study employed 16S rRNA gene sequencing and metabolic profiling to monitor the dynamic colonization of the RYGB microbial consortium and their metabolic impact on the host. Eleven Wistar rats received vancomycin and enrofloxacin, followed by fecal microbiota transplantation (FMT) of cecal slurry obtained from either RYGB- or sham-operated rats. Urine and feces from the microbiota recipients (RYGB microbiota recipients [RYGBr], n = 6; sham microbiota recipients [SHAMr], n = 5) were collected pre- and post-antibiotics and 1, 3, 6, 9, and 16 days post-FMT. No significant differences in body weight and food intake were observed between RYGBr and SHAMr. While neither group reached the community richness of that of their donors, by day 6, both groups reached the richness and diversity of that prior to antibiotic treatment. However, the typical signature of RYGB microbiome-increased Enterobacteriaceae-was not replicated in these recipients after two consecutive FMT, suggesting that the environmental changes induced by the anatomical rearrangements of RYGB could be key for sustaining such a consortium. The transplanted bacteria did not induce the same metabolic signature of urine and feces as those previously reported in RYGB-operated rats. Future work is required to explore environmental factors that shape the RYGB microbiota in order to further investigate the metabolic functions of the RYGB microbiota, thereby teasing out the mechanisms of the RYGB surgery.IMPORTANCE Roux-en-Y gastric bypass (RYGB) surgery results in a long-term gut bacterial shift toward Gammaproteobacteria in both patients and rodents. The contribution of this compositional shift, or the RYGB bacterial consortium, to the metabolic benefit of the surgery remains debatable. It is unclear how well these bacteria colonize in an anatomically normal gut. This is a fundamental question in both defining the function of the RYGB microbiota and evaluating its potential as a nonsurgical treatment for obesity. We monitored the dynamic colonization of the RYGB bacterial consortium and observed that while approximately one-third of the bacterial taxa from the RYGB donor colonized in the gut of the nonoperated recipients, Gammaproteobacteria were unable to colonize for longer than 3 days. The study highlighted that a successful long-term colonization of Gammaproteobacteria-rich RYGB microbiota in nonsurgical animals requires key environmental factors that may be dictated by the intestinal anatomical modification by the surgery itself.

A natural mutation in Pisum sativum L. (pea) alters starch assembly and improves glucose homeostasis in humans.

Elevated postprandial glucose (PPG) is a significant risk factor for non-communicable diseases globally. Currently, there is a limited understanding of how starch structures within a carbohydrate-rich food matrix interact with the gut luminal environment to control PPG. Here, we use pea seeds (Pisum sativum) and pea flour, derived from two near-identical pea genotypes (BC1/19RR and BC1/19rr) differing primarily in the type of starch accumulated, to explore the contribution of starch structure, food matrix and intestinal environment to PPG. Using stable isotope 13C-labelled pea seeds, coupled with synchronous gastric, duodenal and plasma sampling in vivo, we demonstrate that maintenance of cell structure and changes in starch morphology are closely related to lower glucose availability in the small intestine, resulting in acutely lower PPG and promotion of changes in the gut bacterial composition associated with long-term metabolic health improvements.

Does Sleeve Gastrectomy Expose the Distal Esophagus to Severe Reflux?: A Systematic Review and Meta-analysis.

OBJECTIVE: The aim of this study was to appraise the prevalence of gastroesophageal reflux disease (GERD), esophagitis, and Barrett's esophagus (BE) after sleeve gastrectomy (SG) through a systematic review and meta-analysis. BACKGROUND: The precise prevalence of new-onset or worsening GERD after SG is controversial. Subsequent esophagitis and BE can be a serious unintended sequalae. Their postoperative prevalence remains unclear. METHODS: A systematic literature search was performed to identify studies evaluating postoperative outcomes in primary SG for morbid obesity. The primary outcome was prevalence of GERD, esophagitis, and BE after SG. Meta-analysis was performed to calculate combined prevalence. RESULTS: A total of 46 studies totaling 10,718 patients were included. Meta-analysis found that the increase of postoperative GERD after sleeve (POGAS) was 19% and de novo reflux was 23%. The long-term prevalence of esophagitis was 28% and BE was 8%. Four percent of all patients required conversion to RYGB for severe reflux. CONCLUSIONS: The postoperative prevalence of GERD, esophagitis, and BE following SG is significant. Symptoms do not always correlate with the presence of pathology. As the surgical uptake of SG continues to increase, there is a need to ensure that surgical decision-making and the consent process for this procedure consider these long-term complications while also ensuring their postoperative surveillance through endoscopic and physiological approaches. The long-term outcomes of this commonly performed bariatric procedure should be considered alongside its weight loss and metabolic effects.

Taste Changes after Bariatric Surgery: a Systematic Review.

BACKGROUND: Alterations in taste perception and preferences may contribute to dietary changes and subsequent weight loss following bariatric surgery. METHODS: A systematic search was performed to identify all articles investigating gustation, olfaction, and sensory perception in both animal and human studies following bariatric procedures. RESULTS: Two hundred fifty-five articles were identified after database searches, bibliography inclusions and deduplication. Sixty-one articles were included. These articles provide evidence supporting changes in taste perception and hedonic taste following bariatric procedures. Taste sensitivity to sweet and fatty stimuli appears to increase post-operatively. Additionally, patients also have a reduced hedonic response to these stimuli. CONCLUSIONS: Available evidence suggests that there is a change in taste perception following bariatric procedures, which may contribute to long-term maintenance of weight loss following surgery.

Correction to: Treatment of Obesity in Young People-a Systematic Review and Meta-analysis.

In the original article, due to a production error, the text for the "Principle Findings" section was omitted as was the heading for the "Strengths and Limitations" section. The original article has been updated to correct these errors.

A Prospective Metagenomic and Metabolomic Analysis of the Impact of Exercise and/or Whey Protein Supplementation on the Gut Microbiome of Sedentary Adults.

Many components of modern living exert influence on the resident intestinal microbiota of humans with resultant impact on host health. For example, exercise-associated changes in the diversity, composition, and functional profiles of microbial populations in the gut have been described in cross-sectional studies of habitual athletes. However, this relationship is also affected by changes in diet, such as changes in dietary and supplementary protein consumption, that coincide with exercise. To determine whether increasing physical activity and/or increased protein intake modulates gut microbial composition and function, we prospectively challenged healthy but sedentary adults with a short-term exercise regime, with and without concurrent daily whey protein consumption. Metagenomics- and metabolomics-based assessments demonstrated modest changes in gut microbial composition and function following increases in physical activity. Significant changes in the diversity of the gut virome were evident in participants receiving daily whey protein supplementation. Results indicate that improved body composition with exercise is not dependent on major changes in the diversity of microbial populations in the gut. The diverse microbial characteristics previously observed in long-term habitual athletes may be a later response to exercise and fitness improvement. IMPORTANCE The gut microbiota of humans is a critical component of functional development and subsequent health. It is important to understand the lifestyle and dietary factors that affect the gut microbiome and what impact these factors may have. Animal studies suggest that exercise can directly affect the gut microbiota, and elite athletes demonstrate unique beneficial and diverse gut microbiome characteristics. These characteristics are associated with levels of protein consumption and levels of physical activity. The results of this study show that increasing the fitness levels of physically inactive humans leads to modest but detectable changes in gut microbiota characteristics. For the first time, we show that regular whey protein intake leads to significant alterations to the composition of the gut virome.

Treatment of Obesity in Young People-a Systematic Review and Meta-analysis.

Obesity in the young is increasingly prevalent. Early, effective intervention is paramount. Treatment options are lifestyle modifications, pharmacological therapies, endoscopic treatments and bariatric surgery. However, the relative effectiveness of these treatments in young patients remains unclear. We systematically identify and meta-analyse studies evaluating weight loss treatments in young people (< 21 years) with obesity. From 16,372 identified studies, 83 were eligible for meta-analysis. Bariatric surgery resulted in high short/medium-term weight loss (pooled estimate 14.04 kg/m2). Lifestyle and pharmacological therapies impacted weight more moderately (pooled estimate 0.99 and 0.94 kg/m2 respectively). Due to its high efficacy, bariatric surgery should be considered earlier when treating obesity in young people. However, due to the invasiveness and inherent risks of bariatric surgery, all other weight loss routes should be exhausted first.

The microbiome of professional athletes differs from that of more sedentary subjects in composition and particularly at the functional metabolic level.

OBJECTIVE: It is evident that the gut microbiota and factors that influence its composition and activity effect human metabolic, immunological and developmental processes. We previously reported that extreme physical activity with associated dietary adaptations, such as that pursued by professional athletes, is associated with changes in faecal microbial diversity and composition relative to that of individuals with a more sedentary lifestyle. Here we address the impact of these factors on the functionality/metabolic activity of the microbiota which reveals even greater separation between exercise and a more sedentary state. DESIGN: Metabolic phenotyping and functional metagenomic analysis of the gut microbiome of professional international rugby union players (n=40) and controls (n=46) was carried out and results were correlated with lifestyle parameters and clinical measurements (eg, dietary habit and serum creatine kinase, respectively). RESULTS: Athletes had relative increases in pathways (eg, amino acid and antibiotic biosynthesis and carbohydrate metabolism) and faecal metabolites (eg, microbial produced short-chain fatty acids (SCFAs) acetate, propionate and butyrate) associated with enhanced muscle turnover (fitness) and overall health when compared with control groups. CONCLUSIONS: Differences in faecal microbiota between athletes and sedentary controls show even greater separation at the metagenomic and metabolomic than at compositional levels and provide added insight into the diet-exercise-gut microbiota paradigm.

Small bowel malignant melanoma presenting as a perforated jejunal diverticulum: a case report and literature review.

Although usually harmless and asymptomatic, jejuno-ileal diverticulae are associated with various non-specific gastrointestinal symptoms, and rarely cause surgical emergencies. This case report describes the presentation and management of a patient with an acute abdomen, whose jejunal diverticulum was perforated. Unexpectedly, histopathological assessment demonstrated malignant melanoma lining the diverticulum. Whether this was primary or metastatic is discussed, together with a synopsis of the literature on small bowel diverticulae.

Laparoscopic management of Bouveret syndrome.

Bouveret syndrome is a proximal form of gallstone ileus where a large gallstone lodges in the pylorus or proximal duodenum, having passed through a bilioenteric fistula that has formed secondary to previous cholecystitis. We describe the laparoscopic extraction of a giant 'Bouveret' gallstone from the duodenum of an elderly man with morbid obesity.

1H NMR global metabolic phenotyping of acute pancreatitis in the emergency unit.

We have investigated the urinary and plasma metabolic phenotype of acute pancreatitis (AP) patients presenting to the emergency room at a single center London teaching hospital with acute abdominal pain using (1)H NMR spectroscopy and multivariate modeling. Patients were allocated to either the AP (n = 15) or non-AP patients group (all other causes of abdominal pain, n = 21) on the basis of the national guidelines. Patients were assessed for three clinical outcomes: (1) diagnosis of AP, (2) etiology of AP caused by alcohol consumption and cholelithiasis, and (3) AP severity based on the Glasgow score. Samples from AP patients were characterized by high levels of urinary ketone bodies, glucose, plasma choline and lipid, and relatively low levels of urinary hippurate, creatine and plasma-branched chain amino acids. AP could be reliably identified with a high degree of sensitivity and specificity (OPLS-DA model R(2) = 0.76 and Q(2)Y = 0.59) using panel of discriminatory biomarkers consisting of guanine, hippurate and creatine (urine), and valine, alanine and lipoproteins (plasma). Metabolic phenotyping was also able to distinguish between cholelithiasis and colonic inflammation among the heterogeneous non-AP group. This work has demonstrated that combinatorial biomarkers have a strong diagnostic and prognostic potential in AP with relevance to clinical decision making in the emergency unit.

A meta-analysis of probiotic and synbiotic use in elective surgery: does nutrition modulation of the gut microbiome improve clinical outcome?

BACKGROUND: Perioperative nutrition modulation of gut microbiota is increasingly used as a strategy for reducing the infective complications of elective surgery. This meta-analysis assessed the effect of probiotic and synbiotic preparations on the incidence of postoperative sepsis. METHODS: Randomized controlled trials that compared preoperative dosing of probiotics and synbiotics in patients undergoing elective general surgical procedures were included. The primary outcome measure was the postoperative sepsis rate. Pooled outcome measures were determined using random effects models. RESULTS: Thirteen randomized controlled trials totaling 962 patients were included in this analysis (304 received synbiotics and 182 received probiotics). The incidence of postoperative sepsis was reduced in the probiotic group vs the control (pooled odds ratio [OR] = 0.42; 95% confidence interval [CI], 0.23-0.75; P = .003) and in the synbiotic group vs the control (pooled OR = 0.25; 95% CI, 0.1-0.6; P = .002). However, subgroup analysis failed to identify a significant reduction in the incidence of pneumonia, urinary tract infections, or wound infections in the postoperative phase for either treatment group. Synbiotics reduced the length of postoperative antibiotic use (weighted mean differences = -1.71; 95% CI, -3.2 to -0.21; P = .03). CONCLUSION: Probiotic and synbiotic nutrition strategies reduce the incidence of postoperative sepsis in the elective general surgery setting. These effects appear more pronounced with the use of synbiotics. High-powered, mechanistic studies are now required for the optimization of pro- and prebiotic regimens to further improve their efficacy.

A rare combination of rare conditions: Salmonella septic sacroiliitis and hepatitis.

We report an unusual presentation of sacroiliitis and hepatitis secondary to Salmonella systemic infection. A high index of suspicion, early blood cultures, prompt investigations and treatment with parenteral antibiotics can result in complete resolution of symptoms and prevent long-term sequelae of either condition.

The gut microbiota as a target for improved surgical outcome and improved patient care.

The 'gut origin of sepsis' concept describes the role of the intestine in the development of sepsis and the post-operative Multi Organ Dysfunction Syndrome (MODS). Translocation of the microbiota from the gut into the systemic milieu is thought to be integral to this process. However, advances in molecular biology have demonstrated numerous mechanisms of interkingdom signalling within the gut and evidence suggests that the gut microbiota may directly influence the mammalian phenotype. The gut ecosystem fluctuates significantly in response to exogenous and surgical trauma yet until recently it has not been possible to study this non invasively and thus it is not known how current perioperative infection control strategies influence the microbiome and the consequences of this intervention for the host. However, novel analytical techniques such as metabonomics and metagenomics are permitting the in vivo analysis of the gut microbiome and are creating new avenues of research that have significant surgical applications. Furthermore, the protective mechanisms of commensal biota are increasingly being recognised, suggesting that perioperative modulation of the gut microbiome with pre, pro and synbiotics may beneficially influence surgical outcome. This paper reviews the role of the gut microbiome in determining surgical outcome, and highlights research into the mammalian microbial symbiotic axis which is leading to novel therapeutic interventions in surgery.