Amylose resistant starch (HAM-RS2) supplementation increases the proportion of Faecalibacterium bacteria in end-stage renal disease patients: Microbial analysis from a randomized placebo-controlled trial.

INTRODUCTION: Many of the deleterious effects associated with chronic kidney disease (CKD) are secondary to the resultant systemic inflammation. The gut microbial changes caused by CKD are thought to perpetuate systemic inflammation. Therefore, strategies aimed at modulating the gut microbiota may be helpful in reducing complications associated with CKD. We hypothesized that supplementation with high-amylose maize resistant starch type 2 (HAM-RS2) would beneficially alter the gut microbiome and lead to lower levels of systemic inflammation. METHODS: A double-blind, parallel, randomized, placebo-controlled trial was performed comparing dietary supplementation of HAM-RS2 with placebo in patients with end-stage CKD. Fecal microbial data were obtained from a subset of patients after DNA extraction and 16s sequencing. FINDINGS: Supplementation of HAM-RS2 led to a decrease in serum urea, IL-6, TNFα, and malondialdehyde (P < 0.05). The Faecalibacterium genus was significantly increased in relative abundance following HAM-RS2 supplementation (HAM-RS2-Day 0: 0.40 ± 0.50 vs. HAM-RS2-Day 56: 3.21 ± 4.97 P = 0.03) and was unchanged by placebo (Control-Day 0: 0.72 ± 0.72 vs. Control-Day 56: 0.83 ± 1.57 P = 0.5). DISCUSSION: Supplementation of amylose resistant starch, HAM-RS2, in patients with CKD led to an elevation in Faecalibacterium and decrease in systemic inflammation. Microbial manipulation in CKD patients by using the prebiotic fiber may exert an anti-inflammatory effect through an elevation in the bacterial genera Faecalibacterium.

The success of fecal microbial transplantation in Clostridium difficile infection correlates with bacteriophage relative abundance in the donor: a retrospective cohort study.

Background: Fecal microbial transplantation (FMT) is used in the treatment of relapsing Clostridium difficile infection (rCDI). Failure rate for FMT is as high as 10% but the mechanisms contributing to a failed FMT are not understood. We utilized metagenomic data to identify the role of bacteria and bacteriophages on FMT success.Results: Subjects with rCDI (n = 19) received FMT from volunteer donors (n = 7) via colonoscopy. Twelve patients fully recovered after a single FMT, while seven patients required a subsequent FMT. DNA was extracted from patient and donor stool samples for shotgun metagenomic analysis. Metagenomics libraries were analyzed focusing on bacterial taxonomy and bacteriophage sequences. Gammaproteobacteria were dominant in rCDI patients prior to FMT largely due to elevated levels of Klebsiella and Escherichia. A successful FMT led to increased levels of Clostridia and Bacteroidia and a reduction in Gammaproteobacteria. In contrast, a failed FMT led to no significant changes in bacterial composition. Bacteriophages were classified during whole metagenomic analysis of each sample and were markedly different between rCDI patients, donors, and a healthy control cohort (n = 96). Bacteriophage sequence reads were increased in CDI patients compared with donors and healthy controls. Successful FMT donors had higher bacteriophage α-diversity and lower relative abundance compared to the donors of a failed initial FMT.Conclusions: In this retrospective analysis, FMTs with increased bacteriophage α-diversity were more likely to successfully treat rCDI. In addition, the relative number of bacteriophage reads was lower in donations leading to a successful FMT. These results suggest that bacteriophage abundance may have some role in determining the relative success of FMT.

Endospore forming bacteria may be associated with maintenance of surgically-induced remission in Crohn's disease.

Crohn's disease (CD) patients who undergo ileocolonic resection (ICR) typically have disease recurrence at the anastomosis which has been linked with a gut dysbiosis. The aims of this study were to define the mucosa-associated microbiota at the time of ICR and to determine if microbial community structure at the time of surgery was predictive of future disease relapse. Ileal biopsies were obtained at surgery and after 6 months from CD subjects undergoing ICR. Composition and function of mucosal-associated microbiota was assessed by 16S rRNA sequencing and PICRUSt analysis. Endoscopic recurrence was assessed using the Rutgeerts score. Analysis of mucosal biopsies taken at the time of surgery showed that decreased Clostridiales together with increased Enterobacteriales predicted disease recurrence. An increase in the endospore-forming Lachnospiraceae from surgery to 6 months post-ICR was associated with remission. A ratio of 3:1 between anaerobic endospore-forming bacterial families and aerobic families within the Firmicutes phylum was predictive of maintenance of remission. Gut recolonization following ICR is facilitated by microbes which are capable of either aerobic respiration or endospore formation. The relative proportions of these species at the time of surgery may be predictive of subsequent microbial community restoration and disease recurrence.

A BACH2 Gene Variant Is Associated with Postoperative Recurrence of Crohn's Disease.

BACKGROUND: Crohn's disease often requires intestinal resection, which is not considered curative. Repeat surgical intervention is necessary in more than half of patients after their initial operation. Although many genetic loci are implicated in Crohn's disease, few have been associated with post-resection recurrence. STUDY DESIGN: A cohort of patients with Crohn's disease who underwent intestinal resection was analyzed to determine genetic and clinical factors associated with post-resection recurrence. Genotype was assessed at 8 loci associated with adaptive immunity (SMAD3, IL10RB, IL15RA, BACH2, IL12B, IL18RAP, IFNGR2, and JAK2). Univariate and multivariable survival analyses were performed using a log-rank test and Cox-proportional hazard model, respectively. RESULTS: One hundred and ninety-one patients with Crohn's disease and 11.2 years mean postoperative follow-up were included. Forty-six percent experienced a surgical recurrence. Factors associated with increased incidence of recurrence included male sex (p = 0.05) and shortened time to first intestinal operation (5.0 vs 7.3 years; p = 0.03); inflammatory disease behavior was associated with a lower chance of repeat operation (p < 0.01). Of the loci assessed on multivariable analysis, homozygosity for a risk allele at BACH2 (rs1847472) was significantly associated with disease recurrence (hazard ratio 1.54; 95% CI 1.00 to 2.36; p < 0.05). CONCLUSIONS: We identify BACH2 as a susceptibility locus for postoperative recurrence of Crohn's disease in our cohort. BACH2 is critical in the differentiation and function of T cells, as a regulator of B-cell activity, and is associated with several dysregulated immunologic phenomena. Its identification as a risk locus in postoperative Crohn's disease recurrence suggests a potential role for regulatory T cells, effector T cells, humoral immunity, and immunologic memory in the development of this disease process.

The Use of a Pre-operative Carbohydrate Drink in Patients with Diabetes Mellitus: A Prospective, Non-inferiority, Cohort Study.

BACKGROUND: Pre-operative fasting leads to insulin resistance and increased metabolic stress in non-diabetic patients. Consumption of a carbohydrate drink may alleviate these deleterious effects. Patients with diabetes mellitus represent over 15% of the surgical population, yet concerns over hyperglycemia and aspiration have excluded patients with diabetes mellitus from studies assessing the utility of pre-operative carbohydrate drinks. OBJECTIVE: To assess for a clinically significant increase in pre-operative blood glucose concentration (defined as >2 mmol/L) in patients with diabetes consuming a pre-operative carbohydrate drink. METHODS: A prospective observational non-inferiority cohort study of 106 subjects with diabetes mellitus was undertaken to assess the effect of consuming a pre-operative carbohydrate drink in surgical patients. All patients with diabetes mellitus undergoing surgery (including but not limited to cardiac, neurologic, urologic, and general surgical procedures) were enrolled. Subjects were instructed to consume two carbohydrate-rich drinks, one before sleeping the evening prior to surgery and another on the day of surgery. RESULTS: In total, 43% of subjects were fully compliant with the pre-operative carbohydrate drink regimen. There were no significant differences between the fully compliant and non-compliant subjects with respect to baseline characteristics. Consumption of a pre-operative carbohydrate drink was determined to be non-inferior to fasting in terms of pre-operative blood glucose concentration (absolute difference 0.23 mmol/L, 95% CI: -1.00 to 1.45 mmol/L, p non-inferiority < 0.01). Neither group was found to be superior in terms of pre-operative blood glucose concentration, hyperglycemia, or length of stay. CONCLUSIONS: These findings function as a step toward ensuring pre-operative carbohydrate drinks are safe in patients with diabetes undergoing surgery.