Urban-Rural Disparities and Temporal Trends in Peptic Ulcer Disease Epidemiology, Treatment, and Outcomes in the United States.

INTRODUCTION: The incidence of peptic ulcer disease (PUD) has been decreasing over time with Helicobacter pylori eradication and use of acid-suppressing therapies. However, PUD remains a common cause of hospitalization in the United States. We aimed to evaluate contemporary national trends in the incidence, treatment patterns, and outcomes for PUD-related hospitalizations and compare care delivery by hospital rurality. METHODS: Data from the National Inpatient Sample were used to estimate weighted annual rates of PUD-related hospitalizations. Temporal trends were evaluated by joinpoint regression and expressed as annual percent change with 95% confidence intervals (CIs). We determined the proportion of hospitalizations requiring endoscopic and surgical interventions, stratified by clinical presentation and rurality. Multivariable logistic regression was used to assess independent predictors of in-hospital mortality and postoperative morbidity. RESULTS: There was a 25.8% reduction (P < 0.001) in PUD-related hospitalizations from 2005 to 2014, although the rate of decline decreased from -7.2% per year (95% CI: 13.2% to -0.7%) before 2008 to -2.1% per year (95% CI: 3.0% to -1.1%) after 2008. In-hospital mortality was 2.4% (95% CI: 2.4%-2.5%). Upper endoscopy (84.3% vs 78.4%, P < 0.001) and endoscopic hemostasis (26.1% vs 16.8%, P < 0.001) were more likely to be performed in urban hospitals, whereas surgery was performed less frequently (9.7% vs 10.5%, P < 0.001). In multivariable logistic regression, patients managed in urban hospitals were at higher risk for postoperative morbidity (odds ratio 1.16 [95% CI: 1.04-1.29]), but not death (odds ratio 1.11 [95% CI: 1.00-1.23]). DISCUSSION: The rate of decline in hospitalization rates for PUD has stabilized over time, although there remains significant heterogeneity in treatment patterns by hospital rurality.

Predicting surgical site infections following laparoscopic bariatric surgery: development of the BariWound tool using the MBSAQIP database.

BACKGROUND: Although bariatric surgery is a safe procedure for severe obesity, incisional surgical site infections (SSI) remain a significant cause of morbidity. Bariatric surgery patients are at high risk due to obesity and diabetes. The objective of this study was to develop a predictive tool for incisional SSI within 30 days of bariatric surgery. METHODS: Data were retrieved from the 2015 and 2016 MBSAQIP databases. This study included patients who underwent primary laparoscopic Roux-en-Y gastric bypass (LRYGB) or laparoscopic sleeve gastrectomy (LSG). The primary outcome of interest was incisional SSI occurring within 30 days. Surgeries performed in 2015 were used in a derivation cohort and the predictive tool was validated against the 2016 cohort. A forward selection algorithm was used to build a logistic regression model predicting probability of SSI. RESULTS: A total of 274,187 patients were included with 71.7% being LSG and 28.3% LRYGB. 0.7% of patients had a SSI in which 71.0% had an incisional SSI, and 29.9% had an organ/space SSI. Of patients who had an incisional SSI, 88.7% were superficial, 10.9% were deep, and 0.4% were both. A prediction model to assess for risk of incisional SSI, BariWound, was derived and validated. BariWound consists of procedure type, chronic steroid or immunosuppressant use, gastroesophageal reflux disease, obstructive sleep apnea, sex, type 2 diabetes, hypertension, operative time, and body mass index. It stratifies individuals into very high (> 10%), high (5-10%), medium (1-5%), and low risk (< 1%) groups. This model accurately predicted events in the validation cohort with an area under the receiver operating characteristic curve of 0.73. CONCLUSIONS: BariWound accurately predicted the risk of 30-day incisional SSI in individuals undergoing bariatric surgery. Stratifying low- and high-risk groups allows for customized SSI prophylactic measures for patients in various risk categories and potentially enables future research targeted at high-risk patients.

Predicting venous thromboembolism following laparoscopic bariatric surgery: development of the BariClot tool using the MBSAQIP database.

BACKGROUND: Bariatric surgery is an effective treatment for severe obesity; however, postoperative venous thromboembolism (VTE) remains a leading cause of morbidity and mortality. The objective of this study is to develop a tool to stratify individuals undergoing laparoscopic bariatric surgery according to their 30-day VTE risk. METHODS: This is a retrospective cohort study of the Metabolic and Bariatric Surgery Accreditation and Quality Improvement Program (MBSAQIP) database. This registry collects data specific for metabolic or bariatric surgery with 30-day outcomes from 791 centers. Individuals undergoing primary laparoscopic Roux-en-Y gastric bypass (LRYGB) or laparoscopic sleeve gastrectomy (LSG) were included. Characteristics associated with 30-day VTE were identified using univariate and multivariable analyses. A predictive model, BariClot, was derived from a randomly-generated derivation cohort using a forward selection algorithm. BariClot's robustness was tested against a validation cohort of subjects not included in the derivation cohort. The calibration and discrimination of two previously published VTE risk tools were assessed in the MBSAQIP population and compared to BariClot. RESULTS: A total of 274,221 patients underwent LRYGB or LSG. Overall, 1106 (0.4%) patients developed VTE, 452 (0.2%) developed pulmonary embolism, and 43 (0.02%) died due to VTE. VTE was the most commonly identified cause of 30-day mortality. A prediction model to assess for risk of VTE, BariClot, was derived and validated. BariClot consists of history of VTE, operative time, race, and functional status. It stratifies individuals into very high (> 2%), high (1-2%), medium (0.3-1%), and low risk groups (< 0.3%). This model accurately predicted events in the validation cohort and outperformed previously published scoring systems. CONCLUSIONS: BariClot is a predictive tool that stratifies individuals undergoing bariatric surgery based on 30-day VTE risk. Stratifying low- and high-risk populations for VTE allows for informed clinical decision-making and potentially enables further research on customized prophylactic measures for low- and high-risk populations.

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.

Enhanced Recovery After Surgery (ERAS®) in Individuals with Diabetes: A Systematic Review.

BACKGROUND: Prevalence of diabetes in surgical patients is 10-40%. It is well recognized that they have higher rates of complications, and longer stays in hospital compared to patients without diabetes. Enhanced recovery after surgery (ERAS) is an evidence-based multimodal surgical care pathway that improves postoperative complications and length of stay in patients without diabetes. This review evaluates the evidence on whether individuals with diabetes would benefit from ERAS implementation. METHODS: MEDLINE, Cochrane Central Register of Controlled Trials (CENTRAL) and EMBASE searched with no language restrictions applied. Conference proceedings and bibliographies were reviewed. Experts in the field were contacted, and www.clinicaltrials.gov searched for ongoing trials. SELECTION CRITERIA: Randomized controlled trials (RCT) looking at individuals with diabetes undergoing surgery randomized to ERAS® or conventional care. Non-randomized controlled trials, controlled before-after studies, interrupted time series, and cohort studies with concurrent controls were also considered. Two authors independently screened studies. RESULTS: The electronic search yielded 437 references. After removing duplicates, 376 were screened for eligibility. Conference proceedings and bibliographies identified additional references. Searching www.clinicaltrials.gov yielded 59 references. Contacting experts in the field identified no further studies. Fourteen full articles were assessed and subsequently excluded for the following reasons: used an intervention other than ERAS®, did not include patients with diabetes, or used an uncontrolled observational design. CONCLUSIONS: To date, the effects of ERAS® on patients with diabetes have not been rigorously evaluated. This review highlights the lack of evidence in this area and provides guidance on design for future studies.

Age-related disparities and trends in national healthcare spending for management of appendicitis in the United States: A retrospective cost-analysis.

BACKGROUND: Changes in clinical care for appendicitis have impacted healthcare use associated with treatment. We evaluated national trends and assessed factors associated with healthcare costs for appendicitis in the United States. DESIGN: The Disease Expenditure Project, the Global Burden of Disease study, and the National Inpatient Sample were used to estimate total national expenditures, per-capita costs for incident cases, and factors associated with inpatient costs for appendicitis management, respectively. The national estimates of appendicitis costs were obtained from 1996 to 2016. Appendicitis incidence was estimated to calculate per-capita costs. After application of survey weights for the stratified sample design, 191,180 weighted discharges for appendicitis from the 2016 National Inpatient Sample study were evaluated. The Disease Expenditure Project and the Global Burden of Disease study were used to estimate total and per-capita spending. Temporal trends were evaluated using joinpoint regression, expressed as annual percent change. Multivariable linear regression was used to evaluate patient factors associated with total hospital charges. RESULTS: In 2016, total spending on appendicitis was $9.3 billion (95% confidence interval: $8.0-$10.8], a 2-fold increase from $4.7 billion ($4.0-$5.3) in 1996. Per-capita spending decreased significantly after 2011 (annual percent change -3.7% [-4.4% to -2.9%]). Patients ≥65 years accounted for 64.1% (61.1%-67.3%) of total spending for appendicitis. The hospital charges for older patients were significantly higher among those undergoing appendectomy. CONCLUSION: Overall healthcare spending for appendicitis has doubled from 1996 to 2016, but per capita spending has decreased since 2011, driven by improved efficiency of inpatient care. Nearly two-thirds of spending is on patients ≥65 years, with significantly higher costs associated with surgical management in this population.

Roux-en-Y gastric bypass and sleeve gastrectomy induce substantial and persistent changes in microbial communities and metabolic pathways.

Bariatric surgery induces significant microbial and metabolomic changes, however, links between microbial and metabolic pathways have not been fully elucidated. The objective of this study was to conduct a comprehensive investigation of the microbial, metabolomic, and inflammatory changes that occur following Roux-en-Y gastric bypass (RYGB) and sleeve gastrectomy (SG). A prospective clinical trial was conducted with participants undergoing RYGB, SG, and non-operative controls (CTRL). Clinical parameters, blood samples, and fecal samples were collected pre-intervention and at 3 and 9 months. A multi-omics approach was used to perform integrated microbial-metabolomic analysis to identify functional pathways in which weight loss and metabolic changes occur after surgery. RYGB led to profound microbial changes over time that included reductions in alpha-diversity, increased Proteobacteria and Verrucomicrobiota, decreased Firmicutes, and numerous changes at the genera level. These changes were associated with a reduction in inflammation and significant weight loss. A reduction in Romboutsia genera correlated strongly with weight loss and integrated microbial-metabolomic analysis revealed the importance of Romboutsia. Its obliteration correlated with improved weight loss and insulin resistance, possibly through decreases in glycerophospholipids. In contrast, SG was associated with no changes in alpha-diversity, and only a small number of changes in microbial genera. A cluster of Firmicutes genera including Butyriciccocus, Eubacterium ventriosum, and Monoglobus was decreased, which correlated with decreased weight, insulin resistance, and systemic inflammation. This work represents comprehensive analyses of microbial-metabolomic changes that occur following bariatric surgery and identifies several pathways that are associated with beneficial metabolic effects of surgery.

The Genetics of Postoperative Recurrence in Crohn Disease: A Systematic Review, Meta-analysis, and Framework for Future Work.

Background: Recurrence following abdominal surgery in Crohn disease is over 50%. The impact of genetics on postoperative recurrence is not well defined. Methods: A literature search was conducted where inclusion required an assessment, by genotype, of postoperative recurrence. The primary endpoint was odds of surgical recurrence. Results: Twenty-eight studies identified a total of 6715 patients. Thirteen loci were identified as modifying the risk of recurrence. NOD2 was identified as a risk factor for recurrence by multiple works (cumulative odds ratio: 1.64, P = 0.003). Conclusions: A NOD2 risk allele is associated with recurrence following surgery in Crohn disease. Progress in this area will require standardized reporting in future works.

Timing of Tributyrin Supplementation Differentially Modulates Gastrointestinal Inflammation and Gut Microbial Recolonization Following Murine Ileocecal Resection.

BACKGROUND: Gastrointestinal surgery imparts dramatic and lasting imbalances, or dysbiosis, to the composition of finely tuned microbial ecosystems. The aim of the present study was to use a mouse ileocecal resection (ICR) model to determine if tributyrin (TBT) supplementation could prevent the onset of microbial dysbiosis or alternatively enhance the recovery of the gut microbiota and reduce gastrointestinal inflammation. METHODS: Male wild-type (129 s1/SvlmJ) mice aged 8-15 weeks were separated into single cages and randomized 1:1:1:1 to each of the four experimental groups: control (CTR), preoperative TBT supplementation (PRE), postoperative TBT supplementation (POS), and combined pre- and postoperative supplementation (TOT). ICR was performed one week from baseline assessment with mice assessed at 1, 2, 3, and 4 weeks postoperatively. Primary outcomes included evaluating changes to gut microbial communities occurring from ICR to 4 weeks. RESULTS: A total of 34 mice that underwent ICR (CTR n = 9; PRE n = 10; POS n = 9; TOT n = 6) and reached the primary endpoint were included in the analysis. Postoperative TBT supplementation was associated with an increased recolonization and abundance of anaerobic taxa including Bacteroides thetaiotomicorn, Bacteroides caecimuris, Parabacteroides distasonis, and Clostridia. The microbial recolonization of PRE mice was characterized by a bloom of aerotolerant organisms including Staphylococcus, Lactobacillus, Enteroccaceae, and Peptostreptococcacea. PRE mice had a trend towards decreased ileal inflammation as evidenced by decreased levels of IL-1ß (p = 0.09), IL-6 (p = 0.03), and TNF-α (p < 0.05) compared with mice receiving TBT postoperatively. In contrast, POS mice had trends towards reduced colonic inflammation demonstrated by decreased levels of IL-6 (p = 0.07) and TNF-α (p = 0.07). These changes occurred in the absence of changes to fecal short-chain fatty acid concentrations or histologic injury scoring. CONCLUSIONS: Taken together, the results of our work demonstrate that the timing of tributyrin supplementation differentially modulates gastrointestinal inflammation and gut microbial recolonization following murine ICR.

A Protocol for Roux-en-Y Gastric Bypass in Rats using Linear Staplers.

Roux-en-Y gastric bypass (RYGB) is commonly performed for the treatment of severe obesity and type 2 diabetes. However, the mechanism of weight loss and metabolic changes are not well understood. Multiple factors are thought to play a role, including reduced caloric intake, decreased nutrient absorption, increased satiety, the release of satiety-promoting hormones, shifts in bile acid metabolism, and alterations in the gut microbiota. The rat RYGB model presents an ideal framework to study these mechanisms. Prior work on mouse models have had high mortality rates, ranging from 17 to 52%, limiting their adoption. Rat models demonstrate more physiologic reserve to surgical stimulus and are technically easier to adopt as they allow for the use of surgical staplers. One challenge with surgical staplers, however, is that they often leave a large gastric pouch which is not representative of RYGB in humans. In this protocol, we present a RYGB protocol in rats that result in a small gastric pouch using surgical staplers. Utilizing two stapler fires which remove the forestomach of the rat, we obtain a smaller gastric pouch similar to that following a typical human RYGB. Surgical stapling also results in better hemostasis than sharp division. Additionally, the forestomach of the rat does not contain any glands and its removal should not alter the physiology of RYGB. Weight loss and metabolic changes in the RYGB cohort were significant compared to the sham cohort, with significantly lower glucose tolerance at 14 weeks. Furthermore, this protocol has an excellent survival of 88.9% after RYGB. The skills described in this protocol can be acquired without previous microsurgical experience. Once mastered, this procedure will provide a reproducible tool for studying the mechanisms and effects of RYGB.

Ileal microbial shifts after Roux-en-Y gastric bypass orchestrate changes in glucose metabolism through modulation of bile acids and L-cell adaptation.

Roux-en-Y gastric bypass (RYGB)-induced glycemic improvement is associated with increases in glucagon-like-peptide-1 (GLP-1) secreted from ileal L-cells. We analyzed changes in ileal bile acids and ileal microbial composition in diet-induced-obesity rats after RYGB or sham surgery to elucidate the early and late effects on L-cells and glucose homeostasis. In early cohorts, there were no significant changes in L-cell density, GLP-1 or glucose tolerance. In late cohorts, RYGB demonstrated less weight regain, improved glucose tolerance, increased L-cell density, and increased villi height. No difference in the expression of GLP-1 genes was observed. There were lower concentrations of ileal bile acids in the late RYGB cohort. Microbial analysis demonstrated decreased alpha diversity in early RYGB cohorts which normalized in the late group. The early RYGB cohorts had higher abundances of Escherichia-Shigella but lower abundances of Lactobacillus, Adlercreutzia, and Proteus while the late cohorts demonstrated higher abundances of Escherichia-Shigella and lower abundances of Lactobacillus. Shifts in Lactobacillus and Escherichia-Shigella correlated with decreases in multiple conjugated bile acids. In conclusion, RYGB caused a late and substantial increase in L-cell quantity with associated changes in bile acids which correlated to shifts in Escherichia-Shigella and Lactobacillus. This proliferation of L-cells contributed to improved glucose homeostasis.

A high-sugar diet rapidly enhances susceptibility to colitis via depletion of luminal short-chain fatty acids in mice.

Western-style diets have been implicated in triggering inflammatory bowel disease activity. The aim of this study was to identify the effect of a short-term diet high in sugar on susceptibility to colitis. Adult wild-type mice were placed on chow or a high sugar diet (50% sucrose) ± acetate. After two days of diet, mice were treated with dextran sodium sulfate (DSS) to induce colitis. Disease severity was assessed daily. Colonic tissues were analyzed for cytokine expression using the MesoScale discovery platform. Intestinal dextran permeability and serum lipopolysaccharide levels (LPS) were measured. Gut microbiota were analyzed by 16s rRNA sequencing and short chain fatty acid (SCFA) concentrations by gas chromatography. Bone marrow-derived macrophages (BMDM) were incubated with LPS and cytokine secretion measured. Mice on a high sugar diet had increased gut permeability, decreased microbial diversity and reduced SCFA. BMDM derived from high sugar fed mice were highly responsive to LPS. High sugar fed mice had increased susceptibility to colitis and pro-inflammatory cytokine concentrations. Oral acetate significantly attenuated colitis in mice by restoring permeability. In conclusion, short term exposure to a high sugar diet increases susceptibility to colitis by reducing short-chain fatty acids and increasing gut permeability.

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.

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.

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.

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.

Fecal Microbiota Transplantation: Beyond Clostridium difficile.

PURPOSE OF REVIEW: Fecal microbiota transplantation (FMT) has been established as standard of care in the treatment of antibiotic refractory Clostridium difficile infection (RCDI). This review examines the current evidence that exists to support the use of FMT in the treatment of human disease beyond C. difficile infection. RECENT FINDINGS: Beneficial effects of FMT have been described in case series or small prospective trials on a wide spectrum of conditions, including inflammatory bowel disease, functional gastrointestinal disorders, non-alcoholic steatohepatitis, alcoholic hepatitis, hepatic encephalopathy, and neuropsychiatric conditions, and in limiting antibiotic-resistant bacterial infections. Each of these proposed indications for FMT is associated with an underlying dysbiosis of the gastrointestinal microbiota and generally a clinical response is linked with a restoration of the gut microbiota. The potential of fecal microbial transplantation to alter disease course shows promise but further large-scale studies are necessary to understand limitations as well as how best to utilize this therapy.

Fecal microbial transplantation as a therapeutic option in patients colonized with antibiotic resistant organisms.

Despite increasing interest in fecal microbiota transplantation (FMT), its full therapeutic potential has yet to be determined. Since its increase in popularity, FMT has been shown to be highly effective in the treatment of both Clostridium difficile infection (CDI) and its recurrent form. Interest in FMT now expands well beyond the treatment of CDI to other processes with known associations to the microbiota such as antibiotic resistant infections, inflammatory bowel disease (IBD), hepatic encephalopathy, neuropsychiatric disorders, and metabolic disease. The rampant use and misuse of antibiotics in both medicine and agriculture has resulted in an increase in antibiotic resistant organisms which pose a significant risk to human health. The purpose of this commentary is to address the general issue of antibiotic resistance in the human microbiota and the restorative potential of FMT in this area.