Links between gut microbiome, metabolome, clinical variables and non-alcoholic fatty liver disease severity in bariatric patients.

BACKGROUND AND AIMS: Bacterial species and microbial pathways along with metabolites and clinical parameters may interact to contribute to non-alcoholic fatty liver disease (NAFLD) and disease severity. We used integrated machine learning models and a cross-validation approach to assess this interaction in bariatric patients. METHODS: 113 patients undergoing bariatric surgery had clinical and biochemical parameters, blood and stool metabolite measurements as well as faecal shotgun metagenome sequencing to profile the intestinal microbiome. Liver histology was classified as normal liver obese (NLO; n = 30), simple steatosis (SS; n = 41) or non-alcoholic steatohepatitis (NASH; n = 42); fibrosis was graded F0 to F4. RESULTS: We found that those with NASH versus NLO had an increase in potentially harmful E. coli, a reduction of potentially beneficial Alistipes putredinis and an increase in ALT and AST. There was higher serum glucose, faecal 3-(3-hydroxyphenyl)-3-hydroxypropionic acid and faecal cholic acid and lower serum glycerophospholipids. In NAFLD, those with severe fibrosis (F3-F4) versus F0 had lower abundance of anti-inflammatory species (Eubacterium ventriosum, Alistipes finegoldii and Bacteroides dorei) and higher AST, serum glucose, faecal acylcarnitines, serum isoleucine and homocysteine as well as lower serum glycerophospholipids. Pathways involved with amino acid biosynthesis and degradation were significantly more represented in those with NASH compared to NLO, with severe fibrosis having an overall stronger significant association with Superpathway of menaquinol-10 biosynthesis and Peptidoglycan biosynthesis IV. CONCLUSIONS: In bariatric patients, NASH and severe fibrosis were associated with specific bacterial species, metabolic pathways and metabolites that may contribute to NAFLD pathogenesis and disease severity.

Relationship between dietary intake components and hepatic fibrosis in those with obesity before and 1 year after bariatric surgery.

OBJECTIVES: Non-alcoholic fatty liver disease is highly prevalent in the bariatric population but not all patients develop liver fibrosis. Considering that fibrosis may affect clinical outcomes, it is important to assess and treat contributing factors. In this population, it is not clear whether dietary intake is a contributor. The objective was to determine the relationship between dietary intake components and liver fibrosis before and 1 y after Roux-en-Y gastric bypass (RYGB). METHODS: This was a prospective cross-sectional (n = 133) study conducted between 2013 and 2022. In addition, a subgroup of 44 patients were followed for 1 y post-RYGB. Anthropometrics, biochemical measurements, and 3-d food records and liver biopsies were obtained presurgery and, in a subgroup of patients, as for the cohort, 1 y post-RYGB. RESULTS: In the cross-sectional study, 78.2% were female, with a median age of 48 y and body mass index of 46.8 kg/m2; 33.8% had type 2 diabetes mellitus and 57.1% had metabolic syndrome. In a multivariate analysis, age (odds ratio; 95% CI) (1.076; 1.014-1.141), alanine transaminase (1.068; 1.025-1.112), calorie intake (1.001; 1.000-1.002), and dietary copper (0.127; 0.022-0.752) were independently associated with fibrosis (<0.05). At 1 y post-RYGB, no independent risk factors were associated with persistent fibrosis. CONCLUSIONS: In bariatric patients before surgery, higher age, alanine transaminase, and total calorie and lower copper intakes were independent risk factors associated with liver fibrosis. These relationships were no longer observed after RYGB, likely due to the effect of surgery on weight and similar postsurgery diet among patients.

Adult patients with short bowel syndrome treated with teduglutide: A descriptive cohort study.

BACKGROUND: Teduglutide is a synthetic glucagon-like peptide-2 analogue approved for the treatment of short bowel syndrome associated with chronic intestinal failure (SBS-IF) in adult patients. Clinical trials have demonstrated its ability to reduce parenteral support (PS) requirement. This study aimed to describe the effect of 18-month treatment with teduglutide, evaluating PS and factors associated with PS volume reduction of ≥20% from baseline and weaning. Two-year clinical outcomes were also assessed. METHODS: This descriptive cohort study collected data prospectively from adult patients with SBS-IF treated with teduglutide and enrolled in a national registry. Data were collected every 6 months and included demographics, clinical, biochemical, PS regimen, and hospitalizations. RESULTS: Thirty-four patients were included. After 2 years, 74% (n = 25) had a PS volume reduction of ≥20% from baseline, and 26% (n = 9) achieved PS independency. PS volume reduction was significantly associated with longer PS duration, significantly lower basal PS energy intake, and absence of narcotics. PS weaning was significantly associated with fewer infusion days, lower PS volume, longer PS duration, and lower narcotics use at baseline. Alkaline phosphatase was significantly lower in weaned patients after 6 and 18 months of treatment. During the 2-year study duration, patients who had PS volume reduction of ≥20% had significantly fewer yearly hospitalizations and hospital-days. CONCLUSIONS: Teduglutide reduces PS volume and promotes weaning in adults with SBS-IF. Lack of narcotics and longer PS duration were associated with PS volume reduction and weaning, and lower baseline PS volume and fewer infusion days were favorable in obtaining enteral autonomy.

In critically ill adult patients with COVID-19, lower energy and higher protein intake are associated with fewer mechanical ventilation and antibiotic days but not with ICU length of stay.

BACKGROUND: Coronavirus disease 2019 (COVID-19) nutrition management guidelines recommend hypocaloric, high-protein feeding in the acute phase of critical illness. This study aimed to determine, among critically ill adults with COVID-19, whether nutrition support affects outcomes in nonobese patients when providing a mean energy intake of ≥20 kcal/kg/day vs <20 kcal/kg/day and protein intake of ≥1.2 g/kg/day vs <1.2 g/kg/day, using actual body weight, and in patients with obesity when providing ≥20 kcal/kg/day vs <20 kcal/kg/day and a protein intake of ≥2 g/kg/day vs <2 g/kg/day using ideal body weight. METHODS: This retrospective study included adults with COVID-19 on mechanical ventilation (MV) admitted to the intensive care unit (ICU) from 2020 to 2021. Clinical and nutrition parameters were recorded the first 14 days of ICU stay. RESULTS: One hundred four patients were included: 79 (75.96%) were male and had a median age of 51 years and body mass index of 29.65 kg/m2 . ICU length of stay (LOS) was not affected by nutrition intake, but patients receiving <20 kcal/kg/day had fewer MV days (P = 0.029). In a subgroup analysis, MV days were lower in the nonobese group receiving <20 kcal/kg/day (P = 0.012). In the obese group, those receiving higher protein intake had fewer antibiotic days (P = 0.013). CONCLUSION: In critically ill patients with COVID-19, lower energy and higher protein intake were respectively associated with fewer MV days and, in patients with obesity, fewer antibiotic days, but they had no effect on ICU LOS.

Adipose Tissue and Plasma Markers Associated with HbA1c Pre- and Post-bariatric Surgery: a Cross-sectional and Cohort Study.

PURPOSE: Obesity can be associated with chronic inflammation and dysregulated expression of inflammatory adipokines that contribute to insulin resistance and type 2 diabetes. This may also affect the clinical response to bariatric surgery. Our objective was whether baseline visceral adipose tissue features and plasma adipokine are associated with HbA1c ≥0.06 at the time of Roux-en-Y gastric bypass (RYGB) surgery and with persistently elevated HbA1c at 12 months post-RYGB. METHODS: During the surgery, adipose biopsies and plasma were collected for adipokine/cytokine profile. Clinical and biochemical measurements were also collected at the time of RYGB and, in those with baseline elevated HbA1c, at 12 months post-RYGB. RESULTS: In the cross-sectional study, 109 patients (82.6% female; age 49 years; BMI 46.98 kg/m2) participated. Of those with elevated HbA1c at baseline (n = 61), 47 patients had repeated measurements at 12 months post-RYGB (23% drop-out). Using a multivariate logistic regression model, older age (adjusted odds ratio (aOR), 1.14; 95% confidence interval (CI), 1.06-1.22) and higher plasma resistin (aOR, 5.30; 95% CI, 1.25-22.44) were associated with higher odds of HbA1c ≥ 0.06, whereas higher plasma adiponectin (aOR, 0.993; 95% CI, 0.99-0.996) was associated with lower odds of HbA1c ≥0.06. In addition, baseline higher average adipose cell area (aOR, 1.0017; 95% CI, 1.0002-1.0032) and plasma resistin (aOR, 1.0004; 95% CI, 1.0000-1.0009) were associated with higher odds of having persistently elevated HbA1c at 12 months post-RYGB. CONCLUSION: Our study suggests that baseline plasma adipokine dysregulation, specifically high resistin, and adipocyte hypertrophy may affect the clinical response to RYGB.

Gut microbiome modified by bariatric surgery improves insulin sensitivity and correlates with increased brown fat activity and energy expenditure.

Alterations in the microbiome correlate with improved metabolism in patients following bariatric surgery. While fecal microbiota transplantation (FMT) from obese patients into germ-free (GF) mice has suggested a significant role of the gut microbiome in metabolic improvements following bariatric surgery, causality remains to be confirmed. Here, we perform paired FMT from the same obese patients (BMI > 40; four patients), pre- and 1 or 6 months post-Roux-en-Y gastric bypass (RYGB) surgery, into Western diet-fed GF mice. Mice colonized by FMT from patients' post-surgery stool exhibit significant changes in microbiota composition and metabolomic profiles and, most importantly, improved insulin sensitivity compared with pre-RYGB FMT mice. Mechanistically, mice harboring the post-RYGB microbiome show increased brown fat mass and activity and exhibit increased energy expenditure. Moreover, improvements in immune homeostasis within the white adipose tissue are also observed. Altogether, these findings point to a direct role for the gut microbiome in mediating improved metabolic health post-RYGB surgery.

Comparing mixed oil to soybean oil lipid emulsion in patients on home parenteral nutrition: a pilot prospective double-blind, crossover, randomized trial.

BACKGROUND: Home parenteral nutrition (HPN) can be associated with increased liver enzymes, catheter-related bloodstream infections (CRBSI), and hospitalizations. Mixed oil (MO) versus soybean oil (SO) lipid emulsion reduces risks in hospitalized patients, but there are no randomized double-blinded controlled trials in HPN. Therefore, the primary objective was to test the study's feasibility such as recruitment and retention in the HPN population and the secondary objective was to assess changes in liver enzymes between MO and SO as well as other clinical and biochemical outcomes. METHODS: This 13-month prospective double-blind crossover randomized pilot trial took place in Toronto, Canada. Participants were HPN patients who were a part of the HPN program at Toronto General Hospital. We recruited patients from the HPN program. HPN patients receiving SO were randomized to either MO or SO, and the study duration was 6 months in each arm (MO or SO) with a 1-month washout period resuming SO. As this is a crossover trial design, the patient is his/her own control. The main outcome measures were descriptions of study feasibility, namely the study recruitment and retention. We also collected biochemical parameters, CRSBI, hospitalization rate, antibiotic use, and mortality. Demographic, nutritional, clinical, and laboratory data were collected at baseline, 3 and 6 months of each arm. The primary analysis population was defined as the per-protocol population who completed the trial including all lipid measurements. RESULTS: A total of 65 HPN patients were assessed, and 60 met the inclusion criteria for the study. Thirty-five percent (21/60) were randomized using a computer-generated random number sequence generator: 10 participants were randomized to receive SO first while 11 were randomized to receive MO first. At 13 months, 3/10 who received SO first completed the study, whereas 9/11 who received MO first completed the study. This did not meet our a priori criteria for success in recruitment and retention. Between types of lipid emulsions, there were no significant differences in changes in liver enzymes or biochemical and clinical outcomes, despite significant changes in plasma free fatty acid composition reflecting MO or SO. CONCLUSIONS: Overall, this pilot trial demonstrated that the use of a prospective double-blind, crossover, randomized trial design was not feasible to conduct in the HPN population because of difficulties in recruiting and retaining patients. In addition, there was no significant impact of MO versus SO lipid emulsion on liver enzymes or most parameters. The lack of significance may be attributed to low sample size from low recruitment and high drop-out rate, short study duration (6 months/arm), and complex care. In a future definitive trial, a multicenter study of longer duration and a larger sample size is recommended, and drop-outs may be reduced by using a parallel study design. TRIAL REGISTRATION: ClinicalTrials.gov, NCT02796833. Registered on 13 June 2016-retrospectively registered.

Effect of faecal microbial transplant via colonoscopy in patients with severe obesity and insulin resistance: A randomized double-blind, placebo-controlled Phase 2 trial.

AIM: To assess the effects of faecal microbial transplant (FMT) from lean people to subjects with obesity via colonoscopy. MATERIAL AND METHODS: In a double-blind, randomized controlled trial, subjects with a body mass index ≥ 35 kg/m2 and insulin resistance were randomized, in a 1:1 ratio in blocks of four, to either allogenic (from healthy lean donor; n = 15) or autologous FMT (their own stool; n = 13) delivered in the caecum and were followed for 3 months. The main outcome was homeostatic model assessment of insulin resistance (HOMA-IR) and secondary outcomes were glycated haemoglobin levels, lipid profile, weight, gut hormones, endotoxin, appetite measures, intestinal microbiome (IM), metagenome, serum/faecal metabolites, quality of life, anxiety and depression scores. RESULTS: In the allogenic versus autologous groups, HOMA-IR and clinical variables did not change significantly, but IM and metabolites changed favourably (P < 0.05): at 1 month, Coprococcus, Bifidobacterium, Bacteroides and Roseburia increased, and Streptococcus decreased; at 3 months, Bacteroides and Blautia increased. Several species also changed significantly. For metabolites, at 1 month, serum kynurenine decreased and faecal indole acetic acid and butenylcarnitine increased, while at 3 months, serum isoleucine, leucine, decenoylcarnitine and faecal phenylacetic acid decreased. Metagenomic pathway representations and network analyses assessing relationships with clinical variables, metabolites and IM were significantly enhanced in the allogenic versus autologous groups. LDL and appetite measures improved in the allogenic (P < 0.05) but not in the autologous group. CONCLUSIONS: Overall, in those with obeisty, allogenic FMT via colonoscopy induced favourable changes in IM, metabolites, pathway representations and networks even though other metabolic variables did not change. LDL and appetite variables may also benefit.

Reliability of Non-invasive Liver Fibrosis Assessment Tools Versus Biopsy in Pre- and Post-bariatric Surgery Patients with Non-alcoholic Fatty Liver Disease.

PURPOSE: Liver biopsy (LBx) remains the gold standard to assess fibrosis in non-alcoholic fatty liver disease (NAFLD). Biochemical markers are also useful, but their reliability is not clear in patients with morbid obesity. We assessed the performance of six non-invasive fibrosis assessment tools before and after bariatric surgery (BSx) using LBx. MATERIALS AND METHODS: This is a cross-sectional and prospective cohort study. LBx was performed at the time of BSx and 12-month post-operatively and assessed using the Brunt system. Clinical and biochemical measurements were collected at the same time points and six non-invasive fibrosis assessment tools were calculated. RESULTS: One hundred seventy patients had BSx; 79.4% female; age was 46.6 ± 9.8 years, and BMI was 48.6 ± 7.5 kg/m2. From liver histology, 88% had F0-F2 and 11.2% F3-F4. At BSx, aspartate aminotransferase to platelet ratio index (APRI) and FIB-4 had better accuracy (0.86 and 0.88) with specificity of 96.6% and 94.0% and negative predictive values (NPV) of 88.9% and 93.7%. However, sensitivity (6.7% and 40.0%) and positive predictive values (PPV) (20.0% and 46.2%) were low. Twelve months post-surgery (n = 54), 88.9% of patients had F0-F2 and 11.1% had F3-F4. Fibrosis-4 index (FIB-4) and NAFLD fibrosis score (NFS) had the best accuracy (0.79 and 0.77) with specificity of 83.7% and 86.9% and NPV of 92.3% and 86.9%. However, sensitivity (25% and 0%) and PPV (12.5% and 0%) were low. CONCLUSION: Overall, FIB-4, APRI, and NFS showed similar performances with higher accuracy, specificity, and NPV. Sensitivity and PPV were low. These tests are more useful at excluding advanced fibrosis.

Relationship Between Hepatic Gene Expression, Intestinal Microbiota, and Inferred Functional Metagenomic Analysis in NAFLD.

INTRODUCTION: We previously reported a lower fecal abundance of Ruminococcus spp., Faecalibacterium prausnitzii , and Coprococcus spp. in nonalcoholic fatty liver disease (NAFLD). In this article, we assess the associations between hepatic gene expression, the specific taxa, and bacterial pathways. METHODS: The relationships between hepatic genes that were differentially expressed in patients with NAFLD vs healthy controls (HC) and the abundance of these specific taxa were studied. Inferred functional metagenomic analysis using Piphillin was also performed to investigate associations with bacterial pathways. RESULTS: Fifteen patients with NAFLD and 6 HC participated. Of 728 hepatic genes examined, 176 correlated with the abundance of Ruminococcus spp., 138 with F. prausnitzii , and 92 with Coprococcus spp. For Ruminococcus spp., genes were enriched in gene ontology (GO) terms related to apoptotic process, response to external and cytokine stimuli, and regulation of signaling. Several genes related to the Kyoto Encyclopedia of Genes and Genomes pathway insulin resistance were correlated with F. prausnitzii . The hepatic genes associated with F. prausnitzii were enriched in GO terms related to cellular response to different stimuli, apoptotic process, and regulation of metabolic pathways. For Coprococcus spp., only the GO term response to external stimulus was enriched. There was a distinct pattern of associations between hepatic genes and bacterial taxa in NAFLD vs HC. For bacterial pathways, 65 and 18 hepatic genes correlated with bacterial metabolic functions in NAFLD and HC, respectively. DISCUSSION: Hepatic gene expression related to insulin resistance, inflammation, external stimuli, and apoptosis correlated with bacterial taxa. Patients with NAFLD showed a higher presence of bacterial pathways associated with lipid metabolism.

Home parenteral nutrition in older vs younger patients: Clinical characteristics and outcomes.

BACKGROUND: There is a demographic shift toward older patients receiving home parenteral nutrition (HPN), but data on clinical outcomes are limited. The objective of this study was to determine differences between older and younger HPN patients in regard to HPN indications, prescriptions, and outcomes over the first 2 years receiving HPN. METHODS: This was a retrospective analysis of prospectively collected data from HPN adult patients entered in the Canadian HPN Registry. New HPN patients enrolled between 2003 and 2017 and receiving HPN for at least 2 years were selected. Data included demographics, PN prescriptions, catheter-related bloodstream infections (CRBSIs) over the past year, survival, and quality of life based on Karnofsky Performance Status (KPS). RESULTS: Four hundred two patients were included: 184 patients were ≥60 years old, and 219 patients were between 18 and 59 years old. There were no differences in the main indications for HPN, body mass index (BMI), and PN prescriptions at baseline. At 2 years, younger patients received more energy from PN than older patients (27.9 vs 19.6 kcal/kg; P < .001), but BMI remained comparable. There were fewer CRBSIs in the older group (20% vs 36%, P = .0023), but 78% of younger patients remained alive vs 69% in the older group (P = .0401). In those alive, the proportion of patients continuing to receive HPN was comparable and the proportion of patients with a KPS ≥60. CONCLUSIONS: Older HPN patients have similar clinical characteristics as younger patients but have fewer CRBSIs and higher 2-year mortality.

Comparison of bioelectrical impedance analysis, mass index, and waist circumference in assessing risk for non-alcoholic steatohepatitis.

OBJECTIVE: Non-alcoholic fatty liver disease is a leading cause of liver disease worldwide and includes nonalcoholic steatohepatitis (NASH), which can progress to cirrhosis. Because NASH is associated with obesity severity, routine evaluation of obesity/body fat in clinical settings may help detect patients at risk. The aim of this study was to determine whether assessing body fat by bioelectrical impedance analysis (BIA) is superior to body mass index (BMI) and waist circumference (WC) in assessing the risk for NASH. METHODS: In this cross-sectional study, patients were recruited and gave consent from a local hospital. All had a liver biopsy. Measurements before the biopsy included BMI, WC, and BIA. BIA was used to measure percentage body fat and fat mass (kg). Based on histology, patients were grouped into one of three categories: simple steatosis (SS), NASH, or normal liver (NL). RESULTS: Of the 139 participants who participated, 39 were classified as SS, 53 as NASH, and 47 as NL. Regardless of sex, patients with NASH had significantly higher BMI, WC, percentage body fat and fat mass than those with NL or SS. These four parameters were significantly positively correlated with liver histology measurements. In all patients, when controlling for sex and age we found that BMI, WC, and BIA were equal at predicting the presence of NASH (P = 0.0571). CONCLUSION: All three methods, BIA, BMI, and WC, were comparable in assessing the risk for NASH. For practical purpose in clinical settings, using BMI is acceptable.

Home parenteral nutrition patients on mixed oil lipid emulsion have a higher rate of hospitalizations compare to those on soybean oil- a prospective 2-year cohort study.

BACKGROUND & AIMS: Mixed oil intravenous lipid emulsion (MO ILE) that contains 30% soybean oil (SO), 30% medium chain triglycerides, 25% olive oil and 15% fish oil can benefit hospitalized patients receiving parenteral nutrition (PN) but there are very few studies on its long-term use. Our goal was to evaluate the clinical outcomes of adults receiving home PN (HPN) with MO versus those receiving SO ILE over a 2-year period. METHOD: This is a retrospective analysis of data collected prospectively from a cohort of patients recorded in the Canadian HPN Registry over a 2-year period. HPN patients from academic programs across Canada were entered in the Registry according to a validated protocol. For this study, demographic, nutritional, laboratory and clinical data were extracted from January 1st 2015, when MO lipid emulsion became available in Canada, to July 24th 2019. Clinical data for each patient included: number of hospitalizations, number of hospitalizations related to HPN and number of hospitalization days related to HPN, over a year; incidence of line sepsis per 1000 catheter days and mortality. Data are presented as median (1st, 3rd quartile) for continuous variables and frequency (percentage) for categorical variables. Comparisons between groups were performed using two sample t-test or Wilcoxon Rank Sum tests for continuous variables and Chi-square tests or Fisher's exact tests for categorical variables. Univariate and multiple linear regressions were also carried out. Statistical significance is set at a p-value <0.05. RESULTS: A total of 120 patients were included (MO n = 68, SO n = 52). Significant differences at baseline between the two groups were a higher use of Hickman line (62.12% vs 42%, p = 0.038) and more western Canada based hospital care with MO (75% vs 42.31%, p = 0.0002). The MO group had significantly more hospitalizations (p = 0.001), more hospitalizations related to HPN (p = 0.012) and more hospitalization days related to HPN (p = 0.016) per patient per year compared to SO patients. There was no significant difference between groups for line sepsis per 1000 catheter days (MO: 0.05 (0.0, 1.0) vs SO: 0.0 (0.0, 0.22), p = 0.053) or mortality. All other variables, including biochemical variables, were similar between groups. In a multiple regression analysis, the following factors were significantly associated with a greater number of hospitalizations per patient per year: use of MO, high blood glucose from the last recorded value and having died by the end of the study period. CONCLUSION: This 2-year prospective cohort study suggests an increased risk of hospitalization in HPN patients receiving MO lipid emulsion. The long-term effect of using MO lipid emulsion in HPN patients should be further evaluated using a large randomized controlled trial. THE STUDY WAS REGISTERED IN CLINICALTRIALS.GOV: (NCT02299466).

Olive oil-based lipid emulsion is noninferior to soybean oil-based lipid emulsion in the acute care setting: A double-blind randomized controlled trial.

OBJECTIVES: Olive oil (OO)-based intravenous lipid emulsion (IVLE) may have biological advantages for nutrition and inflammation status compared with soybean oil (SO)-based IVLE. We aimed to compare prealbumin levels during infusion of OO- or SO-based IVLE in patients receiving parenteral nutrition in the acute-care setting. METHODS: In this prospective, noninferiority, double blind randomized controlled efficacy trial, patients received either OO-based or SO-based IVLE after providing consent. Biochemical and nutrition parameters were collected at baseline and at 7 to 10 d after initiation of parenteral nutrition. Results are expressed as means (standard deviations). RESULTS: A total of 210 patients completed the study: 102 patients in the SO-based IVLE group and 108 patients in the OO-based IVLE group. Both groups had a significant increase in prealbumin levels from baseline (SO: 0.10 [0.06] versus 0.15 [0.08] g/L; P < 0.0001; OO: 0.11 [0.06] versus 0.16 [0.08] g/L; P < 0.0001), but mean changes between groups were not different (P = 0.53). OO-based IVLE was noninferior to SO-based IVLE in maintaining or increasing serum prealbumin levels, with 20% as the noninferiority margin at follow-up (least square geometric mean ratio [95% CI], 1.10 [0.83,1.47]; P = 0.50). There was a significant improvement in C-reactive protein levels from baseline within each group (SO: 83.24 [69.72] versus 53.4 [59.78] mg/dL; P < 0.0001; OO: 85.13 [68.14] versus 58.75 [60.11] mg/dL; P = 0.004), but mean changes between the groups were not different (P = 0.836). Mortality, length of stay, and infection rates were not different for both groups. CONCLUSIONS: In this study, OO-based IVLE was not inferior to SO-based IVLE in maintaining or increasing the prealbumin level. The improvement of C-reactive protein levels and other clinical outcomes were not different for both groups.

Manipulation of intestinal microbiome as potential treatment for insulin resistance and type 2 diabetes.

PURPOSE: Increasing evidence suggests that the intestinal microbiome (IM) and bacterial metabolites may influence glucose homeostasis, energy expenditure and the intestinal barrier integrity and lead to the presence of systemic low-grade inflammation, all of which can contribute to insulin resistance (IR) and type 2 diabetes (T2D). The purpose of this review is to explore the role of the IM and bacterial metabolites in the pathogenesis and treatment of these conditions. RESULTS: This review summarizes research focused on how to modulate the IM through diet, prebiotics, probiotics, synbiotics and fecal microbiota transplant in order to treat IR and T2D. CONCLUSION: There is an abundance of evidence suggesting a role for IM in the pathogenesis of IR and T2D based on reviewed studies using various methods to modulate IM and metabolites. However, the results are inconsistent. Future research should further assess this relationship.

Factors Affecting Metabolic Outcomes Post Bariatric Surgery: Role of Adipose Tissue.

Obesity is an ever-growing public health crisis, and bariatric surgery (BS) has become a valuable tool in ameliorating obesity, along with comorbid conditions such as diabetes, dyslipidemia and hypertension. BS techniques have come a long way, leading to impressive improvements in the health of the majority of patients. Unfortunately, not every patient responds optimally to BS and there is no method that is sufficient to pre-operatively predict who will receive maximum benefit from this surgical intervention. This review focuses on the adipose tissue characteristics and related parameters that may affect outcomes, as well as the potential influences of insulin resistance, BMI, age, psychologic and genetic factors. Understanding the role of these factors may help predict who will benefit the most from BS.

Patients With Severe Gastrointestinal Dysmotility Disorders Receiving Home Parenteral Nutrition Have Similar Survival As Those With Short-Bowel Syndrome: A Prospective Cohort Study.

INTRODUCTION: Severe gastrointestinal dysmotility disorder (GID) constitute approximately 20% of patients requiring home parenteral nutrition (HPN), whereas short-bowel syndrome (SBS) remains the most frequent indication for HPN. This study's aim was to characterize GID patients and compare clinical parameters and survival to SBS patients. Similarly, clinical comparisons between sclerodermaand nonscleroderma patients were made. METHODS: Demographic and clinical data for all patients was extracted from the Canadian HPN Registry from January 1, 2003, to November 1, 2018. Kaplan-Meier method was used to estimate the unadjusted survival probability, and log-rank test was used to compare the survival probability between groups. RESULT: 270 patients (52 GID and 218 SBS) were included in the analysis. For all patients, higher mortality was associated with age (hazard ratio [HR], 1.02 [1.00-1.04]; P = .05), PN dependence (HR, 1.01 [1.00-1.02]; P = .04), hospitalizations (HR, 1.21 [1.10-1.33]; P < .001), and use of immunosuppressant (HR, 1.97 [1.02-3.82]; P = .04). The 5- and 10-year actuarial survival probabilities between GID and SBS were not significantly different (5-year: 70.0% vs 59.2%; 10-year: 79.6% vs 66.2% [P = .5], respectively). There was no difference in survival between scleroderma and nonscleroderma patients (P = .67). CONCLUSION: T5- and 10- year survival probabilities were similar between GID and SBS patients. The diagnosis of scleroderma had no effect on survival. Use of immunosuppressant, older age, PN dependence, and number of hospitalizations per PN duration are risk factors for mortality in both the GID and SBS groups.

Hyposalivation is prevalent in bariatric patients but improves after surgery.

BACKGROUND: Obesity and type 2 diabetes can be associated with poor oral health. This can be because of hyposalivation leading to chronic oral inflammation (OI) and periodontal disease. OBJECTIVE: To assess the prevalence of hyposalivation and OI in individuals undergoing Roux-en-Y gastric bypass (RYGB) and determine the relationship with metabolic and anthropometric parameters before and after RYGB. SETTING: University hospital in Canada. METHODS: This was a cross-sectional and prospective cohort study of 59 patients undergoing RYGB from September 2015 to December 2019. Anthropometric, biochemical, and oral measurements were taken before surgery and 1 and 6 months post RYGB. Oral parameters included salivary flow rate and neutrophil count as marker of OI. RESULTS: Fifty-nine patients were enrolled with 29 completing this study. At baseline, the median age was 47 years and body mass index was 46.5 kg/m2, 52 (88.1%) were female and 14 individuals (23.7%) had type 2 diabetes; 54.2% (n = 32) of patients had hyposalivation and 13.6% (n = 8) had high neutrophil count. Patients with hyposalivation had significantly higher fasting glucose (5.7 mmol/L) compared with those without hyposalivation (5.2 mmol/L) but no difference was found between high versus low neutrophil count. At 6 months post RYGB, all variables except oral neutrophil count significantly improved. Hyposalivation persisted in 7 (24%) individuals. CONCLUSIONS: In our bariatric patients, more than half the patients had hyposalivation before RYGB and this was associated with higher fasting glucose. Hyposalivation improved post RYGB in parallel with improvements in metabolic parameters but there was no change in OI. Increased salivation may reduce the risk of periodontal disease.

Obstructive Sleep Apnea and Non-alcoholic Fatty Liver Disease in Obese Patients Undergoing Bariatric Surgery.

BACKGROUND: Morbid obesity is associated with multiple comorbidities including obstructive sleep apnea (OSA) and non-alcoholic fatty liver disease (NAFLD). It has been suggested that OSA may contribute to NAFLD pathogenesis due to intermittent nocturnal hypoxia. PURPOSE: The objective of this study was to assess the apnea-hypopnea index (AHI) and lower minimum oxygen saturation, markers of OSA, in patients undergoing bariatric surgery (BSx) with perioperative liver biopsy to detect NAFLD. METHODS: This was a single center cross-sectional study of 61 patients undergoing BSx who consented to have a perioperative wedged liver biopsy. Biochemical, clinical, anthropometric variables, and a sleep study test were performed prior to BSx. RESULTS: NAFLD was diagnosed in 49 (80.3%) patients; 12 had normal liver (NL). Those with NAFLD had significantly higher (p < 0.05) AST (42.6 vs 18.1 U/L) and ALT (35.0 vs 22.1 U/L) but similar clinical, anthropometric, and metabolic parameters to NL. There was a higher AHI (32.03 vs 14.35) and significantly lower minimum oxygen saturation (SaO2) (78.87 vs 85.63) in NAFLD compared with NL (p < 0.05). When assessing associations between OSA parameters and liver histology in NAFLD, AHI correlated significantly with lobular inflammation (p < 0.05). In a multivariate analysis, BMI was significantly correlated with lobular inflammation with mean SaO2 nearing significance. CONCLUSIONS: These results indicate that in a homogeneous bariatric population sample with similar characteristics, those with NAFLD had higher AHI and lower minimum SaO2 compared with NL. AHI correlated with liver inflammation suggesting a potential role for intermittent nocturnal hypoxia in the pathogenesis and progression of NAFLD.

Relationships between Atherosclerosis and Plasma Antioxidant Micronutrients or Red Blood Cell Polyunsaturated Fatty Acids in People Living with HIV.

BACKGROUND: People living with human immunodeficiency virus infection and acquired immune deficiency syndrome (HIV/AIDS) (PLWH) are at an increased risk of cardiovascular disease. Diet-related factors may contribute. The aim of this pilot study was to determine, in PLWH, the relationship between atherosclerosis assessed by carotid intima-media thickness (CIMT) and (A) plasma antioxidant micronutrients and oxidative stress or (B) red blood cell polyunsaturated fatty acids (RBC PUFA), particularly long chain omega-3 polyunsaturated fatty acids (n-3 PUFA). METHODS: (A) In a cross-sectional study, subjects had CIMT evaluated by high resolution carotid artery ultrasound. Plasma was collected for vitamin C, measured by spectrophotometry; and alpha- and gamma-tocopherol, retinol, and malondialdehyde-a marker of oxidative stress-using high pressure liquid chromatography and fluorescence spectrophotometry. (B) In a prospective cohort study, other subjects had RBC PUFA measured at baseline, using gas chromatography, and CIMT assessed at baseline and repeated after 2 years. Clinical data was also collected. RESULTS: (A) 91 PLWH participated. Only alpha- and gamma-tocopherol levels were positively correlated with CIMT. In a multivariate analysis, age and systolic blood pressure were significantly associated with CIMT with gamma-tocopherol near significance (p = 0.053). (B) 69 PLWH participated. At baseline, docosahexaenoic acid (n-3 PUFA) and the ratio of docosahexaenoic acid to arachidonic acid (n-6 PUFA) were significantly and negatively correlated with CIMT. However, a multivariate analysis failed to detect a significant relationship either at baseline or 2 years after. CONCLUSION: In addition to age and systolic blood pressure, atherosclerosis assessed by CIMT might be associated with higher serum gamma-tocopherol levels. There was a non-significant association between CIMT and RBC n-3 PUFA or the ratio of n-3 to n-6 PUFA.