APOE Polymorphism Is Associated with Changes in the Kynurenine Pathway.

BACKGROUND: APOE polymorphism and the Kynurenine pathway (KP) are associated with many disorders, but little is known about associations between APOE polymorphism and the KP. This study explored the associations between the KP and APOE polymorphism in disorders associated with APOE polymorphism and changes in the KP. METHODS: Subjects with morbid obesity before and after bariatric surgery (numbers 139 and 95, respectively), depression (number 49), and unspecified neurological symptoms (number 39) were included. The following grouping of the APOE genotypes was used: E2 = ɛ2ɛ2 + ɛ2ɛ3, E3 = ɛ3ɛ3 + ɛ2ɛ4, and E4 = ɛ3ɛ4 + ɛ4ɛ4. The KP metabolites Tryptophan, Kynurenine, Kynurenic acid, Quinolinic acid, and Xanthurenic acid were quantified in serum. RESULTS: The main findings were a significant positive association between E3 and Quinolinic acid (difference between E3 and E2E4: 12.0 (3.5; 18.6) ng/mL); p = 0.005), and a negative association between E4 and Kynurenine (difference between E4 and E2E3: -31.3 (-54.2; -3.2) ng/mL; p = 0.008). Quinolinic acid has been ascribed neurotoxic and inflammatory effects, and Kynurenine is a marker of inflammation. CONCLUSIONS: The findings indicate that APOE polymorphism might cause changes in the KP that contribute to the disease. Inflammation could be the link between APOE and the KP.

The Kynurenine Pathway in Healthy Subjects and Subjects with Obesity, Depression and Chronic Obstructive Pulmonary Disease.

BACKGROUND: Changes in tryptophan metabolism through the kynurenine pathway (KP) are observed in several disorders and coupled with pathophysiological deviations. METHODS: This study retrospectively compared the KP in serum in healthy subjects (108) with subjects with obesity (141), depression (49), and chronic obstructive pulmonary disease (COPD) (22) participating in four clinical studies and explored predictors of the changes in the KP metabolites. RESULTS: Compared with the healthy group, the KP was upregulated in the disease groups with high kynurenine, quinolinic acid (QA), kynurenine/tryptophan-ratio and QA/xanthurenic acid-ratio and low kynurenic acid/QA-ratio. Tryptophan and xanthurenic acid were upregulated in the depressed group compared with the groups with obesity and COPD. The covariates BMI, smoking, diabetes, and C-reactive protein explained the significant differences between the healthy group and the group with obesity but not between the healthy group and the groups with depression and COPD, indicating that different pathophysiological conditions result in the same changes in the KP. CONCLUSIONS: The KP was significantly upregulated in the disease groups compared with the healthy group, and there were significant differences between the disease groups. Different pathophysiological abnormalities seemed to result in the same deviations in the KP.

Do changes in persistent organic pollutants after bariatric surgery cause endocrine disruption?

BACKGROUND: Bariatric surgery results in weight loss, marked endocrine changes and the release of persistent organic pollutants (POPs). The release of POPs might cause endocrine disruption. The study aimed to explore associations between POPs and adiponectin, leptin and ghrelin in subjects undergoing bariatric surgery. METHODS: The study included 63 subjects with severe obesity (men/women: 13/50), age (years): 45.0 (8.5), and BMI (kg/m2) 39.1 (3.4). Analyses of adiponectin, leptin and ghrelin and POPs (hexachlorobenzene (HCB), dichlorodiphenyldichloroethylene (p,p'-DDE), polychlorinated biphenyl (PCB) 118 (dioxin-like compound; dl), and sum 6 PCB (PCB 28, -52, -101, -138, -153, and -180) were performed before and 12 months after bariatric surgery. RESULTS: There were significant increases in adiponectin and all POPs and a fall in leptin after surgery. The main finding was the highly significant associations between adiponectin and all POPs. The increase in HCB explained 38% of the variation in adiponectin. CONCLUSIONS: If the POP-associated increase in adiponectin is a causal effect, the release of POPs might have important clinical consequences. Adiponectin has both positive and negative clinical effects exerted by essentially unknown mechanisms. The effects of released POPs on the metabolic functions in subjects undergoing bariatric surgery deserve further evaluation.

Changes in circulating sirtuin 1 after bariatric surgery.

BACKGROUND AND AIMS: Obesity is associated with chronic inflammation and oxidative stress. Weight loss after bariatric surgery improves the inflammatory state and risk of cardiovascular disease. Improvement in metabolic dysfunction might be associated with changes in the activity of sirtuin 1 (SIRT1) and we aimed to investigate the effect of bariatric surgery on its circulating levels. METHODS AND RESULTS: This is a sub-study of a prospective cohort study, including 110 subjects with morbid obesity. The surgical procedure was either laparoscopic Roux-en-Y gastric bypass (RYGB) or sleeve gastrectomy (SG). Blood was sampled at inclusion and six and 12 months after surgery. SIRT1 was measured in EDTA plasma with an enzyme-linked immunosorbent assay. The mean age in the population was 43 years, 80% were women and mean body mass index (BMI) was 38.8 kg/m2. RYGB and SG were performed in 89 and 21 subjects, respectively. SIRT1 concentration was significantly reduced from baseline to six and 12 months after surgery, with mean values (SD) 156.8 (82.6), 119.5 (65.6) and 94.9 (45.6) ng/mL, respectively, (p ≤ 0.002, all), accompanied by significant reductions in C-reactive protein (CRP), BMI and triglycerides from inclusion (p < 0.001, all). Type of surgery did not differently modify SIRT1 levels (p = 0.09). CRP and triglycerides were both positively predictive of SIRT1 levels (p ≤ 0.001, both). CONCLUSION: SIRT1 concentration was significantly lower six and 12 months after bariatric surgery. CRP and triglycerides independently predicted SIRT1 levels, suggesting that reduction in SIRT1 levels might not intrinsically be related to weight reduction, but to improvement in metaflammation.

Circulating Lipoproteins in Subjects with Morbid Obesity Undergoing Bariatric Surgery with Gastric Bypass or Sleeve Gastrectomy.

The efficacy of various bariatric procedures on the mitigation of the obese dyslipidemia remains debated, and the impact of these measures on lipoprotein(a) (Lp(a)) levels is unknown. In this study we aimed to compare the two most commonly used procedures: gastric bypass (RYGB) and sleeve gastrectomy (SG). Adult patients with morbid obesity were assigned to receive either RYGB or SG. The levels of non-HDL cholesterol, LDL/HDL-ratio and Lp(a) at examinations conducted 6 and 12 months postoperatively were determined and compared to preoperative levels to estimate the efficacy of the two surgical methods. All results 6 and 12 months after surgery were used in the comparisons with the preoperative results. A linear mixed regression model for repeated analyses was used. The Lp(a) and the non-HDL cholesterol levels were considerably reduced in the RYGB group, in contrast to the minor changes in the SG group. In addition, the LDL/HDL ratio was significantly more reduced in the RYGB group when compared to the SG group. Conclusively, RYGB was found to be more efficient than SG for the mitigation of obese dyslipidemia, including preoperative high Lp(a)-levels. This might have important individual and societal implications, especially regarding the potential to reduce the risk of cardiovascular disease and the related societal costs.

APOE Polymorphism and Endocrine Functions in Subjects with Morbid Obesity Undergoing Bariatric Surgery.

BACKGROUND: Obesity is an interplay between genes and the environment, including lifestyle. The genetics of obesity is insufficiently understood. Apolipoprotein E (APOE) genetic polymorphism has been associated with a wide range of disorders. Knowing that some APOE alleles are associated with obesity and endocrine disorders that are common in obesity, the present study aimed at exploring associations between APOE polymorphisms and endocrine functions in subjects with obesity undergoing bariatric surgery. METHODS: Analyses of hormones in blood collected before and one year after bariatric surgery were examined. The APOE alleles were grouped as follows: E2 = ε2ε2 + ε2ε3; E3 = ε3ε3 + ε2ε4; E4 = ε3ε4 + ε4ε4. The APOE groups were analysed as nominal and ordered groups (E2-E3-E4) with a linear mixed model to predict the hormonal effects of the groups. RESULTS: Forty-nine women (79%) and thirteen (21%) men with a mean age of 47.7 (SD 8.5) years were included in the study. The adiponectin level was significantly lower (p < 0.05) in the E2 group compared with the E4 group. Adiponectin and cortisol were positively and negatively associated, respectively, with the ordered APOE groups. CONCLUSIONS: The ordered APOE groups E2-E3-E4 were significantly associated with high and low levels of adiponectin and cortisol, respectively. The findings indicate APOE-mediated effects on body weight and metabolic functions in subjects with morbid obesity.

Reply to Paredes et al. Comment on "Aaseth et al. Circulating Lipoproteins in Subjects with Morbid Obesity Undergoing Bariatric Surgery with Gastric Bypass or Sleeve Gastrectomy. Nutrients 2022, 14, 2381".

Hereby, we thank Silvia Paredes et al. [...].

Are Faecal Microbiota Analyses on Species-Level Suitable Clinical Biomarkers? A Pilot Study in Subjects with Morbid Obesity.

BACKGROUND: An abnormal faecal microbiota could be a causal factor for disease. This study evaluated a new method for faecal microbiota analysis in subjects with obesity and irritable bowel syndrome. METHODS: The study had a matched case-control design. Forty-six subjects with morbid obesity (defined as BMI > 40 or >35 kg/m2 with obesity-related complications) of whom 23 had irritable bowel syndrome (IBS), were compared with 46 healthy volunteers. The faecal microbiota was analysed with Precision Microbiome Profiling (PMP™) which quantified 104 bacteria species. The primary aim was comparisons between the cases and controls. RESULTS: Two men and 44 women with a mean age of 43.6 years were included in each of the groups; BMI in the groups was (mean and SD) 41.9 (3.5) and 22.5 (1.5) kg/m2, respectively. Seventeen bacterial species showed statistically significant differences between the groups after adjusting for multiple testing. In a post hoc analysis, the sensitivity and specificity were 78%. Alpha diversity was lower in the group with obesity. In subjects with morbid obesity, no clinically significant differences were seen between subjects with and without IBS or from before to six months after bariatric surgery. CONCLUSIONS: The results encourage further evaluation of the new microbiome profiling tool.

Changes in serum zonulin in individuals with morbid obesity after weight-loss interventions: a prospective cohort study.

BACKGROUND: Zonulin is a biomarker of impaired intestinal permeability, which has been associated with various disorders. The primary aim was to study serum zonulin (s-zonulin) in individuals with morbid obesity before and after a conservative weight loss intervention followed by bariatric surgery. The secondary aims were to explore predictors of s-zonulin, and the associations between the changes of the predictors and changes in s-zonulin, and to compare the associations in the two treatment periods. METHODS: Individuals with morbid obesity were included. Data before any weight loss interventions, after a 6 months' conservative weight loss intervention, and 6 months after bariatric surgery were used. S-zonulin was measured with an ELISA method from Immundiagnostik AB, Bensheim, Germany. Data were analysed with mixed models. RESULTS: The mean body mass index was 42.1 kg/m2 (SD 3.8) at inclusion and was reduced to 38.7 kg/m2 (SD 3.8) and 29.8 kg/m2 (SD 3.8) after the conservative treatment and bariatric surgery respectively. S-zonulin was 63 ng/mL (SD 32) at inclusion and was reduced with 19 ng/ml (95% CI 12 to 26, p < 0.001) after conservative treatment and 11 ng/ml (95% CI 0 to 21, p = 0.04) after bariatric surgery. At inclusion, s-zonulin was significantly associated with factors including p-glucose (B = 2.21, 95% CI 1.09 to 3.33, p < 0.001), c-reactive protein (B = 1.02, 95% CI 0.45 to 1.58, p < 0.001) and the intake of proteins (B = 0.23, 95% CI 0.08 to 0.38, p = 0.003) and non-nutritive sweeteners (B = 0.68, 95% CI 0.19 to 1.17, p = 0.007). The reduction in s-zonulin after the conservative weight loss intervention was significantly associated with improvement in diarrhoea (B = 6.6, 95% CI 1.3 to 11.8, p = 0.02), HbA1c (B = 9.7, 95% CI 1.1 to 18.3, p = 0.03), p-glucose (B = 3.5, 95% CI 1.2 to 5.9, p = 0.004) and gamma-GT (B = 0.28, 95% CI 0.09 to 0.47, p = 0.004), but not associated with the change in body mass index (B = 0.9, 95% CI - 1.5 to 3.3, p = 0.46). CONCLUSIONS: S-zonulin was markedly reduced after the conservative weight loss intervention, and further reduced after bariatric surgery. The reduction in s-zonulin was associated with improvement of diarrhoea, markers of glucose intolerance and liver disease, but not associated with the change in body mass index.

APOE - a genetic marker of comorbidity in subjects with morbid obesity.

BACKGROUND: In population-based studies, the genetic variability of the APOE E alleles have been associated with health outcomes. Health problems are common in subjects with obesity. This study explored associations between the APOE E alleles and comorbidity in subjects with morbid obesity. METHODS: The study included consecutive subjects referred for evaluation of bariatric surgery with morbid obesity (defined as BMI > 40 or > 35 kg/m2 with complications related to obesity). The subjects followed a conservative weight loss program for 6 months before surgery and had a follow-up visit 12 months after surgery. Demographic data and a set psychosomatic scores (musculoskeletal pain, WHO-5 Well-Being Index, Rosenberg Self-Esteem Scale, Hopkins Symptom Check-list 10; Epworth Sleepiness Scale, and Fatigue Severity Scale) were collected, and blood samples were analysed for haematological and biochemical parameters and APOE alleles. RESULTS: One hundred and forty subjects (men/women: 32 (23%)/108 (77%) with mean age 43.0 (SD 8.7) years and BMI 42.1 (SD 3.8) kg/m2 were included. One hundred and eight and 92 subjects had data after conservative treatment and 12 months after surgery, respectively. The prevalence of the APOE alleles were: E2E2: 1 (0.7%), E2E3: 13 (9.3%), E2E4: 4 (2.9%), E3E3: 71 (50.7%), E3E4: 47 (33.6%), and E4E4: 4 (2.9%). The prevalence rates were as anticipated in a Norwegian population. The weight loss during conservative treatment and after bariatric surgery was independent of E allele variability. E2 was associated with a significant or clear trend toward improvement of all psychosomatic disorders. There was a significant fall in CRP during the two treatment periods with weight loss. E2 and E4 were significantly associated with high and low CRP, respectively, but no associations were seen between CRP and comorbidity. CONCLUSIONS: The most marked finding was the association between E2 and improvement of all psychosomatic disorders. The positive and negative associations between CRP and E2 and E4, respectively, could indicate effects on inflammation and immunological reactions.

Are the Results of a Combined Behavioural and Surgical Treatment of Morbid Obesity Satisfactory and Predictable?

Treatment of subjects with morbid obesity (Body Mass Index (BMI) > 40 kg/m2 or > 35 kg/m2 with obesity-related complications) often fails. This study explored the biopsychosocial predictors of dropout and weight loss during a combined behavioural and surgical weight-reduction program. Behavioural treatment for six months was followed by bariatric surgery and a visit six months after surgery. The success criterion was the loss of ≥50% of excess BMI above 25 kg/m2 (%EBMIL). Thirty-one men and 113 women with BMI 43.5 kg/m2 (SD 4.3) and 41.8 kg/m2 (SD 3.6), respectively, were included; 115 underwent bariatric surgery (Gastric sleeve: 23; Roux-en-Y gastric bypass: 92), and 98 had a follow-up visit six months after surgery. The mean %EBMIL at follow-up was 71.2% (SD 18.5). Treatment success was achieved in 86 subjects. Assuming success in 17 subjects who did not attend the follow-up visit (best possible outcome), 103 out of 144 subjects (72%) achieved successful weight reduction. Cohabitation was the only predictor of accomplishing surgery. Neither weight loss during behavioural therapy nor biopsychosocial factors were found to be clinically significant predictors of weight loss after surgery. The success rate of less than three in four subjects was unsatisfactory. There is a need to improve the regimen and to determine effective alternative interventions.

Changes in Faecal Short-Chain Fatty Acids after Weight-Loss Interventions in Subjects with Morbid Obesity.

The gut microbiota and their metabolites, e.g., short-chain fatty acids (SCFA), are associated with obesity. The primary aims were to study faecal SCFA levels and the changes in SCFA levels after weight-loss interventions in subjects with obesity, and secondarily, to study factors associated with the faecal SCFA levels. In total, 90 subjects (men / women: 15/75) with a mean age of 44.4 (SD 8.4) years, BMI 41.7 (SD 3.7) kg/m2 and morbid obesity (BMI > 40 or > 35 kg/m2 with obesity-related complications) were included. Faecal SCFA and other variables were measured at inclusion and after a six-month conservative weight-loss intervention followed by bariatric surgery (RouxenY gastric bypass or gastric sleeve). Six months after surgery, the total amount of SCFA was reduced, the total and relative amounts of the main straight SCFA (acetic-, propionic-, and butyric- acids) were reduced, and the total and relative amounts of branched SCFA (isobutyric-, isovaleric-, and isocaproic- acids) were increased. The changes indicate a shift toward a proteolytic fermentation pattern with unfavorable health effects. The amount of SCFA was associated with the diet but not with metabolic markers or makers of the faecal microbiota composition. Dietary interventions could counteract the unfavorable effects.

Irritable bowel syndrome-like symptoms and health related quality of life two years after Roux-en-Y gastric bypass - a prospective cohort study.

BACKGROUND: Irritable bowel syndrome (IBS) is prevalent in patients with morbid obesity. After Roux-en-Y gastric bypass (RYGB) chronic abdominal pain is common, however the etiology is largely unknown. We aimed to study the change in the prevalence of IBS-like symptoms 2 years after RYGB and possible preoperative predictors of such symptoms. Secondly, to evaluate changes in symptoms of constipation and diarrhea, and Health related quality of life (HRQoL). METHODS: Patients with morbid obesity were included at two obesity centers in South-Eastern Norway. IBS was diagnosed according to the Rome III criteria. Predictors were evaluated in a multivariable logistic regression analysis. RESULTS: Of 307 participants operated with RYGB, 233 (76%) completed the study questionnaires. Preoperatively 27/233 participants (12%) had IBS, 2 years after RYGB 61/233 (26%) had IBS-like symptoms (p < 0.001). Eleven participants with IBS preoperatively (41%) did not report such symptoms after RYGB. New onset IBS-like symptoms was identified in 45/206 (22%) after RYGB. Fibromyalgia, low LDL levels, high vitamin B1 levels and IBS before RYGB were independent preoperative predictors of IBS-like symptoms at the follow-up visit. Symptom scores for constipation preoperatively and 2 year after RYGB were 1.5 (0.9) and 1.8 (1.2), and for diarrhea 1.4 (0.9) and 1.8 (1.1), respectively (p < 0.001). We observed a significant improvement in the physical component score for all participants. However, participants with new onset IBS-like symptoms had a significant worsening of the mental component score. CONCLUSIONS: The prevalence of IBS-like symptoms doubled 2 years after RYGB, and these symptoms were associated with reduced HRQoL. Preoperative IBS and fibromyalgia were strong predictors of postoperative IBS-like symptoms.

Changes in C-reactive protein, neopterin and lactoferrin differ after conservative and surgical weight loss in individuals with morbid obesity.

C-reactive protein, neopterin and lactoferrin are biomarkers of atherosclerotic disease. We aimed to assess changes in these biomarkers after conservative and surgical weight loss interventions in individuals with morbid obesity, to evaluate associations between biomarker changes and changes in body mass index and HbA1c, and to study associations between changes in the biomarkers. C-reactive protein, neopterin and lactoferrin were measured before and after conservative weight loss intervention and bariatric surgery. Data were analysed with mixed models. 137 individuals (mean age 43 years) were included. Body mass index decreased from 42.1 kg/m2 to 38.9 kg/m2 after the conservative intervention, and further to 30.5 kg/m2 after bariatric surgery. All biomarkers decreased after the conservative weight loss intervention. C-reactive protein and lactoferrin continued to decrease following bariatric surgery whereas neopterin remained stable. After adjustments for change in body mass index and HbA1c, all biomarkers decreased significantly after the conservative weight loss intervention, whereas none changed after bariatric surgery. There were no consistent correlations between changes in C-reactive protein, neopterin and lactoferrin. In conclusion, biomarkers of atherosclerosis decreased after weight loss interventions but had different trajectories. Neopterin, a marker related to atherosclerotic plaque stability, decreased after conservative weight loss but not following bariatric surgery.

Are Nonnutritive Sweeteners Obesogenic? Associations between Diet, Faecal Microbiota, and Short-Chain Fatty Acids in Morbidly Obese Subjects.

Obesity has been associated with changes in the gut microbiota and its metabolites. The study explored changes in the faecal microbiota and short-chain fatty acids (SCFA) associated with the diet (including nonnutritive sweeteners (NNSs)) and evaluated metabolic consequences in subjects with morbid obesity. The diet was assessed with a validated food frequency questionnaire. One unit of NNSs was 100 mL beverage with NNSs or 2 tablets/teaspoons of NNSs. The faecal microbiota was assessed with GA-map® dysbiosis test and SCFA with gas chromatography and flame ionisation detection. Fourteen men and 75 women with a mean age of 44.6 (SD 8.7) years, BMI 41.8 (SD 3.6) kg/m2, and intake of NNSs 7.5 units/day (SD 3.2; range 0-43) were included. Faecal butyric acid was positively and negatively associated with the intake of starch (partial correlation = 0.264; p=0.015) and NNSs (partial correlation = -0.274; p=0.011), respectively. NNSs were associated with changes in four out of 39 bacterial groups. Butyric acid has antiobesogenic effects, reduces insulin resistance, and improves dyslipidaemia. Since the weight-reducing effect of NNSs on obese adults trying to lose weight is dubious, it seems imprudent to use NNSs that might counteract the favourable effects of butyric acid.

Effects of a fall prevention program in elderly: a pragmatic observational study in two orthopedic departments.

PURPOSE: Falls are a common adverse event experienced by elderly in hospitals. This study assessed the effects of a fall prevention program on the rate of fallers, the patient safety culture, and patient-perceived safety. MATERIALS AND METHODS: Two orthopedic departments in different towns in Norway participated in the study. A comprehensive, multifactorial fall prevention program was implemented in one of the departments, the other one was used for control. The changes in the outcomes in the two departments from before to after the intervention were compared. All patients above 64 years of age admitted to the two departments in a 1-year period before and after the intervention were included. All employees at the two departments were invited to participate in surveys measuring the patient safety culture, and a selection of the patients reported patient-perceived safety. The primary outcome was the rate of fallers. Secondary outcomes were the employees' perceived patient safety culture (measured with the Safety Attitudes Questionnaire) and patient-perceived safety (measured with Norwegian Patient Experience Questionnaire). RESULTS: Falls were registered in 114 out of 3,143 patients (3.6%) with 17,006 days in the hospital. Ten patients had two falls, giving a fall rate of 7.3 falls/1,000 days in the hospital. The number of fallers before and after the intervention in the intervention department were 37/734 (5.04%) and 31/735 (4.22%), P=0.46, and in the control department, 25/811 (3.08%) and 21/863 (2.43%), P=0.46. The difference between the changes in the two departments was not statistically significant; 0.17% (95% CI: -2.49 to 2.84; P=0.90). There were also no significant differences in the changes in patient safety culture and patient-perceived safety. CONCLUSION: The fall prevention program revealed no significant effect on the rate of fallers, the patient safety culture, or patient-perceived safety.

Changes in gastrointestinal symptoms and food tolerance 6 months following weight loss surgery: associations with dietary changes, weight loss and the surgical procedure.

BACKGROUND: Gastrointestinal (GI) co-morbidity is common in obese patients, but the effect of weight loss surgery on GI symptoms is incompletely elucidated. The aims of the present study were to explore changes in GI symptoms and food tolerance following weight loss surgery and to study whether such changes were associated with dietary modifications and/or the type of surgical procedure [Roux-en-Y Gastric Bypass (RYGB) versus Vertical Sleeve Gastrectomy (VSG)]. METHODS: Participants: Patients with morbid obesity scheduled for weight loss surgery.The patients filled in paper-based questionnaires addressing diet, GI symptoms (bloating, pain, satiety, constipation and diarrhea) and food tolerance/quality of alimentation (satisfaction about current food intake, tolerance to specific foods and frequency of vomiting/regurgitation/reflux) 6 months prior to and 6 months after the surgery. Patients with pre-existing major GI co-morbidity or previous major GI surgery were excluded. RESULTS: Fifty-four patients (RYGB/VSG: 43/11) were included. Constipation and satiety increased and food tolerance decreased significantly after the surgery (all p-values < 0.05). The increase in satiety was significantly more notable after VSG than after RYGB (p < 0.05).The increase in satiety also correlated with an overall reduction in food tolerance (rho: -0.488, p < 0.01). Divergent changes were seen in the frequency of vomiting/regurgitation/reflux, with a decline after RYGB (p = 0.01) and an increase after VSG (p = 0.06). Intakes of energy, macronutrients, fiber and fluid decreased significantly after the surgery (all p-values < 0.05), but did not correlate with the changes in constipation, satiety or food tolerance (all p-values > 0.05). Pre-operatively, total energy intake correlated with bloating and abdominal pain (rho = 0.343 and 0.310 respectively, p < 0.05 for both), but these correlations did not persist 6 months after the surgery (rho = 0.065 and 0.054 respectively, p > 0.05 for both). CONCLUSION: A high caloric intake may explain some of the GI symptoms experienced by non-operated obese patients. The worsening or new-onset of symptoms post-surgery is likely due to anatomical or physiological alterations following surgery. The increase in satiety and the decrease in food tolerance are likely explained by the restrictive nature of the surgeries, as satiety increased more after VSG than after RYGB and correlated with an overall reduction in food tolerance.

Separating "good" from "bad" faecal dysbiosis - evidence from two cross-sectional studies.

BACKGROUND: Faecal dysbiosis associated with the use of metformin has been conceived as a favourable ("good") dysbiosis and that with intake of non-nutritive sweeteners (NNS) as unfavourable ("bad"). The study aimed to construct an alternative dysbiosis index (ADI) for the separation of the dysbioses into "good" and "bad", and to validate the ADI. METHODS: Subjects with morbid obesity were included. Use of NNS and drugs were noted, IBS was classified according to the Rome III criteria and the severity measured with the Irritable bowel severity scoring system (IBSSS). Faecal dysbiosis was tested with GA-Map ™ Dysbiosis test (Genetic Analysis AS, Oslo, Norway). The result was given as Dysbiosis Index (DI) scores 1-5, score > 2 indicates dysbiosis. An ADI was constructed and validated in subjects with IBS at another hospital. RESULTS: Seventy-six women and 14 men aged 44.7 years (SD 8.6) with BMI 41.8 kg/m2 (SD 3.6) were included. Dysbiosis was associated with the use of NNS and metformin, but not with IBS or IBSSS. An ADI based on differences in 7 bacteria was positively and negatively associated with the "good" metformin dysbiosis and the "bad" NNS dysbiosis respectively. The ADI was also negatively associated with IBSSS (a "bad" dysbiosis). The negative associations between ADI and IBS and IBSS were confirmed in the validation group. CONCLUSIONS: The new ADI, but not the DI, allowed separation of the "good" and "bad" faecal dysbiosis. Rather than merely reporting dysbiosis and degrees of dysbiosis, future diagnostic tests should distinguish between types of dysbiosis.

Faecal Microbial Markers and Psychobiological Disorders in Subjects with Morbid Obesity. A Cross-Sectional Study.

Morbidly obese subjects have a high prevalence of comorbidity and gut microbial dysbiosis, and are thus suitable for the study of gut-brain interactions. The aim was to study the associations between the faecal microbiota's composition and function and psychobiological comorbidity in subjects with BMI > 40 kg/m² or >35 kg/m² with obesity-related complications. The faecal microbiota was assessed with GA-Map dysbiosis test ™ (Genetic Analysis, Oslo Norway) and reported as dysbiosis (yes/no) and degree of dysbiosis, and the relative abundance of 39 bacteria. The microbiota's function was assessed by measuring the absolute and relative amount of faecal short chain fatty acids. Associations were made with well-being, mental distress, fatigue, food intolerance, musculoskeletal pain, irritable bowel syndrome, and degree of abdominal complaints. One hundred and two subjects were included. The results confirmed the high prevalence of comorbidity and dysbiosis (62/102; 61%) and showed a high prevalence of significant associations (41/427; 10%) between the microbiota's composition and function and the psychobiological disorders. The abundant, but in part divergent, associations supported the close gut-brain interaction but revealed no clear-cut and straightforward communication pathways. On the contrary, the study illustrates the complexity of gut-brain interactions.

A Conservative Weight Loss Intervention Relieves Bowel Symptoms in Morbidly Obese Subjects with Irritable Bowel Syndrome: A Prospective Cohort Study.

Background: Irritable bowel syndrome (IBS) is common in subjects with morbid obesity; the effect of weight loss programs on bowel symptoms is largely unknown. Methods: This prospective cohort study explored bowel symptoms, health scores, and biomarkers in subjects with morbid obesity during a six-month-long conservative weight loss intervention. Bowel symptoms were assessed with IBS-severity scoring system (IBS-SSS) and Gastrointestinal Symptom Rating Scale-IBS. Changes in all variables and associations between the changes in bowel symptoms and the other variables were analysed. Results: Eighty-eight subjects (81% females) were included. Body mass index was reduced from 42.0 (3.6) to 38.7 (3.5) (p < 0.001). IBS-SSS was reduced from 116 (104) to 81 (84) (p=0.001). In all, 19 out of 25 variables improved significantly. In subjects with and without IBS at inclusion, the improvement in IBS-SSS was 88 (95% CI 55 to 121) and 10 (95% CI -9 to 29), respectively. Improved bowel symptoms were associated with improved subjective well-being, sense of humour, and vitamin D and negatively associated with reduced body mass index. Conclusion: Body mass index and health scores improved during a conservative weight loss intervention. Subjects with IBS before the intervention had a clinically significant improvement in bowel symptoms.