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Background: Infants with small bowel stomas (SBstoma) frequently struggle with absorption and rely on parenteral nutrition (PN). Intestinal absorption is difficult to predict based solely on intestinal anatomy. The purpose of this study was to characterize the microbiota and metabolic by-products within stoma effluent and correlate with clinical features and intestinal absorption., Methods: Prospective cohort study collecting stoma samples from neonates with SBstoma (N = 23) or colostomy control (N = 6) at initial enteral feed (first sample) and before stoma closure (last sample). Gut bacteriome (16S ribosomal RNA [rRNA] sequencing), short-chain fatty acids (SCFAs) and bile acids (BAs) were characterized along with volume and energy content of a 48 h collection via bomb calorimetry (last sample). Hierarchical clustering and linear regression were used to compare the bacteriome and BAs/SCFAs, to bowel length, PN, and growth., Results: Infants with ≤50% small bowel lost more fluid on average than those with >50% and controls (22, 18, 16 mL/kg/day, p = 0.013), but had similar energy losses (7, 10, 9 kcal/kg/day, p = 0.147). Infants growing poorly had enrichment of Proteobacteria compared to infants growing well (90% vs. 15%, p = 0.004). An increase in the ratio of secondary BAs within the small bowel over time, correlated with poor prognostic factors (≤50% small bowel, >50% of calories from PN, and poor growth)., Conclusion: Infants with SBstoma and poor growth have a unique bacteriome community and those with poor enteral tolerance have metabolic differences compared to infants with improved absorption., (© 2024 The Author(s). Journal of Pediatric Gastroenterology and Nutrition published by Wiley Periodicals LLC on behalf of European Society for Pediatric Gastroenterology, Hepatology, and Nutrition and North American Society for Pediatric Gastroenterology, Hepatology, and Nutrition.)

Introduction: Short bowel syndrome (SBS) is the predominant cause of paediatric intestinal failure. Although life-saving, parenteral nutrition (PN) is linked to complications and may impact quality of life (QoL). Most children will experience intestinal rehabilitation (IR), but the mechanisms underpinning this remain to be understood. SBS is characterised by abnormal microbiome patterns, which might serve as predictive indicators for IR. We aim to characterise the microbiome profiles of children with SBS during IR, concurrently exploring how parental perspectives of QoL relate to IR., Methods and Analysis: This study will enrol a minimum of 20 paediatric patients with SBS (0-18 years). Clinical data and biological samples will be collected over a 2-year study period. We will apply 16S rRNA gene sequencing to analyse the microbiome from faecal and gut tissue samples, with additional shotgun metagenomic sequencing specifically on samples obtained around the time of IR. Gas chromatography with flame ionisation detection will profile faecal short-chain fatty acids. Plasma citrulline and urinary intestinal fatty acid binding proteins will be measured annually. We will explore microbiome-clinical covariate interactions. Furthermore, we plan to assess parental perspectives on QoL during PN and post-IR by inviting parents to complete the Paediatric Quality of Life questionnaire at recruitment and after the completion of IR., Ethics and Dissemination: Ethical approval was obtained from the East Midlands-Nottingham 2 Research Ethics Committee (22/EM/0233; 28 November 2022). Recruitment began in February 2023. Outcomes of the study will be published in peer-reviewed scientific journals and presented at scientific meetings. A lay summary of the results will be made available to participants and the public., Trial Registration Number: ISRCTN90620576., Competing Interests: Competing interests: None declared., (© Author(s) (or their employer(s)) 2024. Re-use permitted under CC BY-NC. No commercial re-use. See rights and permissions. Published by BMJ.)

The exact microbiome composition and function of patients with Short Bowel Syndrome (SBS) and Chronic Intestinal Failure (CIF) are still unknown. Patients with type I SBS-CIF (end-jejunostomy/ileostomy) are little represented in available studies. The aim of this study is to evaluate the microbiome characteristics of adult type 1 SBS-CIF patients according to their clinical features. Fecal microbiota was studied by amplicon-based sequencing and volatile organic compounds (VOCs) were assessed by solid-phase microextraction and gas chromatography-mass spectrometry. A total of 44 adult type 1 SBS-CIF patients were enrolled. At the family level, Lactobacillaceae (38% of the relative frequency) and Streptococcaceae (24%) were predominant; at the genus level, Streptococcus (38% of the relative frequency) and Lactobacillus (24%) were the dominant amplicon sequence variants (ASVs). Patients with increased stomal output showed higher ASVs for Lactobacillus (Rho = +0.38; p = 0.010), which was confirmed after adjusting for small bowel length (OR = 1.04; 95% CI 1.01-1.07, p = 0.023). Hyperphagia was associated with higher concentrations of short-chain fatty acid (SCFA) esters, such as butanoic acid ethyl ester ( p = 0.005) and hexanoic acid ethyl ester ( p = 0.004). Dietary fiber intake was directly correlated with most VOCs. Hyperphagia was associated with dietary fiber, after adjusting for small bowel length (OR = 1.35; 95% CI 1.01-1.81; p = 0.040). In type 1 SBS-CIF patients, a greater frequency of Lactobacilli was associated with increased stomal outputs, while increased fiber intake and concentrations of SCFA esters were associated with hyperphagia. These results might have implications for clinical practice.

Purpose: This study aimed to investigate the impact of hepatocyte growth factor (HGF) on colonic morphology and gut microbiota in a rat model of short bowel syndrome (SBS)., Methods: SD rats underwent jugular vein catheterization for total parenteral nutrition (TPN) and 90% small bowel resection [TPN + SBS (control group) or TPN + SBS + intravenous HGF (0.3 mg/kg/day, HGF group)]. Rats were harvested on day 7. Colonic morphology, gut microflora, tight junction, and Toll-like receptor-4 (TLR4) were evaluated., Results: No significant differences were observed in the colonic morphological assessment. No significant differences were observed in the expression of tight junction-related genes in the proximal colon. However, the claudin-1 expression tended to increase and the claudin-3 expression tended to decrease in the distal colon of the HGF group. The Verrucomicrobiota in the gut microflora of the colon tended to increase in the HGF group. The abundance of most LPS-producing microbiota was lower in the HGF group than in the control group. The gene expression of TLR4 was significantly downregulated in the distal colon of the HGF group., Conclusion: HGF may enhance the mucus barrier through the tight junctions or gut microbiome in the distal colon., (© 2024. The Author(s), under exclusive licence to Springer-Verlag GmbH Germany, part of Springer Nature.)

Objective: Fecal microbiota was investigated in adult patients with chronic intestinal failure (CIF) due to short bowel syndrome (SBS) with jejunocolonic anastomosis (SBS-2). Few or no data are available on SBS with jejunostomy (SBS-1) and CIF due to intestinal dysmotility (DYS) or mucosal disease (MD). We profiled the fecal microbiota of various pathophysiological mechanisms of CIF., Methods: Cross-sectional study on 61 adults with CIF (SBS-1 30, SBS-2 17, DYS 8, MD 6). Fecal samples were collected and profiled by 16S rRNA amplicon sequencing. Healthy controls (HC) were selected from pre-existing cohorts, matched with patients by sex and age., Results: Compared to HC, SBS-1, SBS-2 and MD patients showed lower alpha diversity; no difference was found for DYS. In beta diversity analysis, SBS-1, SBS-2 and DYS groups segregated from HC and from each other. Taxonomically, the CIF groups differed from HC even at the phylum level. In particular, CIF patients' microbiota was dominated by Lactobacillaceae and Enterobacteriaceae, while depleted in typical health-associated taxa belonging to Lachnospiraceae and Ruminococcaceae. Notably, compositional peculiarities of the CIF groups emerged. Furthermore, in the SBS groups, the microbiota profile differed according to the amount of parenteral nutrition required and the duration of CIF., Conclusions: CIF patients showed marked intestinal dysbiosis with microbial signatures specific to the pathophysiological mechanism of CIF as well as to the severity and duration of SBS., Competing Interests: Conflict of interest LP: Participation on Data Safety Monitoring Board or Advisory Board for Takeda; Consulting fees for Takeda, Northsea Therapeutics, NAPO Therapeutics, Nestlè, Lionhealth; Honoraria for lectures by Baxter. FD’A, MG, PB, ASS, ST: none., (Copyright © 2024 Elsevier Ltd and European Society for Clinical Nutrition and Metabolism. All rights reserved.)

Aim: The gastrointestinal bile acid (BA)/microbiota axis has emerged as a potential mediator of health and disease, particularly in relation to pathologies such as inflammatory bowel disease (IBD) and colorectal cancer. Whilst it presents an exciting new avenue for therapies, it has not yet been characterized in surgical resection of the ileum, where BA reabsorption occurs. The identification of BA/microbiota signatures may provide future therapies with perioperative personalized medicine. In this work we conduct a systematic review with the aim of investigating the microbiome and BA changes that are associated with resection of the ileum., Method: The databases included were MEDLINE, EMBASE, Web of Science and Cochrane libraries. The outcomes of interest were faecal microbiome and BA signatures after ileal resection., Results: Of the initial 3106 articles, three studies met the inclusion/exclusion criteria for data extraction. A total of 257 patients (46% surgery, 54% nonsurgery controls) were included in the three studies. Two studies included patients with short bowel syndrome and the other included patients with IBD. Large-scale microbiota changes were reported. In general, alpha diversity had decreased amongst patients with ileal surgery. Phylum-level changes included decreased Bacteroidetes and increased Proteobacteria and Fusobacteria in patients with an intestinal resection. Surgery was associated with increased total faecal BAs, cholic acid and chenodeoxycholic acid. There were decreases in deoxycholic acid and glycine and taurine conjugated bile salts. Integrated BA and microbiota data identified correlations with several bacterial families and BA., Conclusion: The BA/microbiota axis is still a novel area with minimal observational data in surgery. Further mechanistic research is necessary to further explore this and identify its role in improving perioperative outcomes., (© 2024 Association of Coloproctology of Great Britain and Ireland.)

Extensive intestinal resection leads to Short Bowel Syndrome (SBS), the main cause of chronic intestinal failure. Colon preservation is crucial for spontaneous adaptation, to improve absorption and reduce parenteral nutrition dependence. Fecal microbiota transplantation (FMT), a promising approach in pathologies with dysbiosis as the one observed in SBS patients, was assessed in SBS rats with jejuno-colonic anastomosis. The evolution of weight and food intake, the lenght of intestinal villi and crypts and the composition of fecal microbiota of Sham and SBS rats, transplanted or not with high fat diet rat microbiota, were analyzed. All SBS rats lost weight, increased their food intake and exhibited jejunal and colonic hyperplasia. Microbiota composition of SBS rats, transplanted or not, was largely enriched with Lactobacillaceae , and α- and β-diversity were significantly different from Sham. The FMT altered microbiota composition and α- and β-diversity in Sham but not SBS rats. FMT from high fat diet rats was successfully engrafted in Sham, but failed to take hold in SBS rats, probably because of the specific luminal environment in colon of SBS subjects favoring aero-tolerant over anaerobic bacteria. Finally, the level of food intake in SBS rats was positively correlated with their Lactobacillaceae abundance. Microbiota transfer must be optimized and adapted to this specific SBS environment., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2023 Fourati, Dumay, Roy, Willemetz, Ribeiro-Parenti, Mauras, Mayeur, Thomas, Kapel, Joly, Le Gall, Bado and Le Beyec.)

Background: Small bowel bacterial overgrowth (SBBO) is a common, but difficult to diagnose and treat, problem in pediatric short bowel syndrome (SBS). Lack of clinical consensus criteria and unknown sensitivity and specificity of bedside diagnosis makes research on this potential SBS disease modifier challenging. The objective of this research was to describe clinical care of SBBO among international intestinal rehabilitation and nutrition support (IR&NS) providers treating patients with SBS., Methods: A secure, confidential, international, electronic survey of IR&NS practitioners was conducted between March 2021 and May 2021. All analyses were conducted in the R statistical computing framework, version 4.0., Results: Sixty percent of respondents agreed and 0% strongly disagreed that abdominal pain, distension, emesis, diarrhea, and malodorous stool, were attributable to SBBO. No more than 20% of respondents strongly agreed and no more than 40% agreed that any sign or symptom was specific for SBBO. For a first-time diagnosis, 31 practitioners agreed with use of a 7-day course of a single antibiotic, with a majority citing grade 5 evidence to inform their decisions (case series, uncontrolled studies, or expert opinion). The most common first antibiotic used to treat a new onset SBBO was metronidazole, and rifaximin was the second most commonly used. One hundred percent of respondents reported they would consider a consensus algorithm for SBBO, even if the algorithm may be divergent from their current practice., Conclusion: SBBO practice varies widely among experienced IR&NS providers. Development of a clinical consensus algorithm may help standardize care to improve research and care of this complex problem and to identify risks and benefits of chronic antibiotic use in SBS., (© 2022 American Society for Parenteral and Enteral Nutrition.)

Background: Previous studies showed that type 2 short bowel syndrome (SBS) rats were accompanied by severe intestinal bacterial dysbiosis. Limited data are available for intestinal fungal dysbiosis. Moreover, no effective therapeutic drugs are available for these microbiota dysbiosis. The aims of our study were to investigate the therapeutic potential of glucagon-like peptide 2 (GLP-2) for these microbiota dysbiosis in type 2 SBS rats., Methods: 8-week-old male SD rats which underwent 80% small bowel resection, ileocecum resection, partial colon resection and jejunocolostomy, were treated with saline (SBS group, n = 5) or GLP-2 (GLP2.SBS group, n = 5). The Sham group rats which underwent transection and re-anastomosis were given a saline placebo (Sham group, n = 5). 16S rRNA and ITS sequencing were applied to evaluate the colonic bacterial and fungal composition at 22 days after surgery, respectively., Results: The relative abundance of Actinobacteria, Firmicutes and proinflammatory Proteobacteria increased significantly in SBS group rats, while the relative abundance of Bacteroidetes, Verrucomicrobia and Tenericutes decreased remarkably. GLP-2 treatment significantly decreased Proteus and increased Clostridium relative to the saline treated SBS rats. The diversity of intestinal fungi was significantly increased in SBS rats, accompanied with some fungi abnormally increased and some resident fungi (e.g., Penicillium) significantly decreased. GLP-2 treatment significantly decreased Debaryomyces and Meyerozyma, and increased Penicillium. Moreover, GLP-2 partially restored the bacteria-fungi interkingdom interaction network of SBS rats., Conclusion: Our study confirms the bacterial and fungal dysbiosis in type 2 SBS rats, and GLP-2 partially ameliorated these microbiota dysbiosis.

Surgical removal of the intestine, lifesaving in catastrophic gastrointestinal disorders of infancy, can result in a form of intestinal failure known as short bowel syndrome (SBS). Bloodstream infections (BSIs) are a major challenge in pediatric SBS management. BSIs require frequent antibiotic therapy, with ill-defined consequences for the gut microbiome and childhood health. Here, we combine serial stool collection, shotgun metagenomic sequencing, multivariate statistics and genome-resolved strain-tracking in a cohort of 19 patients with surgically-induced SBS to show that antibiotic-driven intestinal dysbiosis in SBS enriches for persistent intestinal colonization with BSI causative pathogens in SBS. Comparing the gut microbiome composition of SBS patients over the first 4 years of life to 19 age-matched term and 18 preterm controls, we find that SBS gut microbiota diversity and composition was persistently altered compared to controls. Commensals including Ruminococcus, Bifidobacterium, Eubacterium , and Clostridium species were depleted in SBS, while pathobionts ( Enterococcus ) were enriched. Integrating clinical covariates with gut microbiome composition in pediatric SBS, we identified dietary and antibiotic exposures as the main drivers of these alterations. Moreover, antibiotic resistance genes, specifically broad-spectrum efflux pumps, were at a higher abundance in SBS, while putatively beneficial microbiota functions, including amino acid and vitamin biosynthesis, were depleted. Moreover, using strain-tracking we found that the SBS gut microbiome harbors BSI causing pathogens, which can persist intestinally throughout the first years of life. The association between antibiotic-driven gut dysbiosis and enrichment of intestinal pathobionts isolated from BSI suggests that antibiotic treatment may predispose SBS patients to infection. Persistence of pathobionts and depletion of beneficial microbiota and functionalities in SBS highlights the need for microbiota-targeted interventions to prevent infection and facilitate intestinal adaptation.

Short bowel syndrome (SBS) is associated with changes in the intestinal microbiome and marked local and systemic inflammation. There is also a late complication of SBS, intestinal failure associated liver disease (IFALD) in which hepatic steatosis progresses to cirrhosis. Most patients with SBS arrive at massive intestinal resection after a contaminating intraabdominal catastrophe and have a history of exposure to broad-spectrum antibiotics. We therefore investigated whether the administration of broad-spectrum antibiotics in conjunction with SBS in zebrafish (ZF) would replicate these systemic effects observed in humans to identify potentially druggable targets to aid in the management of SBS and resulting IFALD. In zebrafish with SBS, broad-spectrum antibiotics altered the microbiome, decreased inflammation, and reduced the development of hepatic steatosis. After two weeks of broad-spectrum antibiotics, these fish exhibited decreased alpha diversity, with less variation in microbial community composition between SBS and sham fish. Additionally, administration of broad-spectrum antibiotics was associated with decreased expression of intestinal toll-like receptor 4 ( tlr 4), increased expression of the intestinal gene encoding the Farnesoid X receptor ( fxr), decreased expression of downstream hepatic cyp7a1 , and decreased development of hepatic steatosis. SBS in zebrafish reproducibly results in increased epithelial surface area as occurs in human patients who demonstrate intestinal adaptation, but antibiotic administration in zebrafish with SBS reduced these gains with increased cell death in the intervillus pocket that contains stem/progenitor cells. These alternate states in SBS zebrafish might direct the development of future human therapies. NEW & NOTEWORTHY In a zebrafish model that replicates a common clinical scenario, systemic effects of the administration of broad-spectrum antibiotics in a zebrafish model of SBS identified two alternate states that led to the establishment of fat accumulation in the liver or its absence. Broad-spectrum antibiotics given to zebrafish with SBS over 2 wk altered the intestinal microbiome, decreased intestinal and hepatic inflammation, and decreased hepatic steatosis.

Background: Children with short bowel syndrome (SBS) frequently struggle with malabsorption and poor growth. The intestinal microbiota plays an important role in gut function, and children with SBS have known deficiencies in some commensal gut microbes. One strategy to enhance the gut microbiota is by taking probiotics. However, the efficacy of this approach is not well established. We hypothesized that probiotic supplementation would result in increased levels of the supplemented bacteria and improved growth., Materials and Methods: Children with SBS who had weaned from parenteral nutrition but with suboptimal growth were randomized to receive probiotics (Lactobacillus rhamnosus and Lactobacillus johnsonii) or placebo daily for 2 mo. The gut microbiota from monthly stool samples were compared between groups using 16S ribosomal ribonucleic acid sequencing and quantitative polymerase chain reaction. Growth between groups was also compared. Statistical analysis was completed using Mann-Whitney, Kruskal-Wallis, and chi-square tests as appropriate., Results: Eighteen children with SBS completed the study (n = 9 per group). There were no significant changes to the major bacterial families in either group. Median relative abundance of Lactobacillus did not differ between groups at baseline or at the end of the study (7.67 versus 13.23, P = 0.523 and 1.93 versus 15.8, P = 0.161). Median z scores for weight and length did not differ between groups at the beginning or end of the study., Conclusions: The efficacy of daily probiotic use in children with intestinal failure is unknown. In this study, Lactobacillus probiotics did not result in a predictable change to the fecal microbiota or overall growth compared with placebo in these patients., (Copyright © 2020 Elsevier Inc. All rights reserved.)

Background and Aim: Studies about differences in microbial communities between the small intestine and colon in infants with short bowel syndrome (SBS) are rare. We aimed to characterize the bacterial diversity of small bowel stoma effluents and feces of SBS infants., Methods: Seven SBS infants were enrolled in this study and provided two samples (one from the stoma and the other from the anus) each. Eleven age-matched healthy controls were recruited to provide one fecal sample each. 16S rRNA gene MiSeq sequencing was conducted to characterize the microbiota diversity and composition., Results: The bacterial diversity of the stoma effluents was significantly higher than that in the feces of SBS infants. Proteobacteria dominated in both the stoma effluents and colonic. Acinetobacter (P = 0.004), Klebsiella (P = 0.015), Citrobacter (P = 0.019), and Lactobacillus (P = 0.030) were more abundant in stoma effluents compared to feces of SBS patients, while Bacteroidetes, Bifidobacterium and Veillonella were less abundant in stoma effluents. Significantly higher levels of Proteobacteria, Enterococcus and lower levels of Blautia, Collinsella, Faecalibacterium, Veillonella were present in the fecal samples of SBS patients than those in the healthy controls. Kyoto Encyclopedia of Genes and Genomes pathways related to metabolism and membrane function were depleted in SBS patients., Conclusions: The predominant intestinal bacterial groups were different in SBS children before and after the fistula closure. Fecal samples of SBS patients featured overabundant Proteobacteria and less SCFA producing bacteria. Depleted functional profiles of the microbiome were found in fecal samples of SBS patients., Level of Evidence: III., (Copyright © 2019 Elsevier Inc. All rights reserved.)

Background: Babies with short bowel syndrome (SBS) have small intestinal microbial disturbances that impact gut function. Characterizing the small bowel microbiota is challenging, and the utility of sampling stool is unclear. This study compares the microbiota from fecal samples and the small bowel., Methods: Stool samples were collected (2016-2017) from infants with SBS and colon in continuity (COLON) or SBS with small bowel ostomy (sbSTOMA). The abundance and quantity of major bacterial genera was compared between groups and to healthy controls using 16S rRNA sequencing and qPCR. Kruskall-Wallis test was used for analysis with P values <0.05 considered significant., Results: Samples (n = 41) were collected from 15 SBS infants (<2 years) (9 sbSTOMA, 6 COLON) and 3 healthy infants. Demographics and small intestinal length did not differ between sbSTOMA and COLON infants. The microbiota of SBS groups differed significantly from healthy controls. Fecal samples contained higher quantities of bacteria, but there were no significant differences between sbSTOMA and COLON groups in the abundance of facultative or obligate anaerobes, anti-inflammatory Clostridia, Enterobacteriaceae, or Bifidobacterium., Conclusion: Infants with SBS have disturbances to their intestinal microbiota. Sampling small intestinal effluent is challenging. Stool samples may provide a window into the more proximal microbial community., Type of Study: Diagnostic., Level of Evidence: Level II., (Copyright © 2020 Elsevier Inc. All rights reserved.)

Background: Short bowel syndrome (SBS) resulting from extensive intestinal resection is thought to significantly affect gut microbiota. Data are limited on the signatures of the intestinal microbiome in SBS with different anatomical types., Aims: The aim of our investigation was to characterize the composition and function of gut microbiota in SBS with or without ileocecal resection (ICR)., Methods: Six-week-old male Sprague-Dawley rats underwent 75% small bowel resection (SBR) with the ileocecal junction intact (SBR group, jejunoileal anastomosis, n = 10) or removed (ICR group, jejunocolic anastomosis, n = 10), or sham surgery (sham group, n = 10). Colonic contents of the rats were collected 28 days after operation, and 16S rRNA gene sequencing was performed on the MiSeq Illumina platform to analyze bacterial composition., Results: Overall structures of the gut microbiome differed significantly among the three groups. The bacterial α-diversity of the ICR group was remarkably lower than that of the sham group. ICR rats were enriched with Lactobacillus and opportunistic pathogens from Proteobacteria but depleted of commensal genera belonging to the Lachnospiraceae, Ruminococcaceae and Erysipelotrichaceae families. Genera from the Bacteroidales S24-7 group, Porphyromonadaceae, Prevotellaceae, Rikenellaceae and Christensenellaceae were prevalent in SBR rats. Functional pathways of branched-chain and aromatic amino acid biosynthesis, lipopolysaccharide biosynthesis and infectious diseases were abundant in the ICR group, while SBR rats featured pathways of C5 branched dibasic acid metabolism, biotin metabolism and one carbon pool folate., Conclusions: ICR causes dramatically more severe intestinal dysbiosis than SBR only in SBS rat models, resulting in altered functional profiles of the gut microbiome.

Background: The gut microbiome and metabolome may significantly influence clinical outcomes in patients with short bowel syndrome (SBS). The study aimed to describe specific metagenomic/metabolomics profiles of different SBS types and to identify possible therapeutic targets., Methods: Fecal microbiome (FM), volatile organic compounds (VOCs), and bile acid (BA) spectrum were analyzed in parenteral nutrition (PN)-dependent SBS I, SBS II, and PN-independent (non-PN) SBS patients., Results: FM in SBS I, SBS II, and non-PN SBS shared characteristic features (depletion of beneficial anaerobes, high abundance of Lactobacilaceae and Enterobacteriaceae). SBS I patients were characterized by the abundance of oxygen-tolerant microrganisms and depletion of strict anaerobes. Non-PN SBS subjects showed markers of partial FM normalization. FM dysbiosis was translated into VOC and BA profiles characteristic for each SBS cohort. A typical signature of all SBS patients comprised high saturated aldehydes and medium-chain fatty acids and reduced short-chain fatty acid (SCFA) content. Particularly, SBS I and II exhibited low protein metabolism intermediate (indole, p-cresol) content despite the hypothetical presence of relevant metabolism pathways. Distinctive non-PN SBS marker was high phenol content. SBS patients' BA fecal spectrum was enriched by chenodeoxycholic and deoxycholic acids and depleted of lithocholic acid., Conclusions: Environmental conditions in SBS gut significantly affect FM composition and metabolic activity. The common feature of diverse SBS subjects is the altered VOC/BA profile and the lack of important products of microbial metabolism. Strategies oriented on the microbiome/metabolome reconstitution and targeted delivery of key compounds may represent a promising therapeutic strategy in SBS patients., (© 2019 American Society for Parenteral and Enteral Nutrition.)

Despite growing literature characterizing the fecal microbiome and its association with health and disease, few studies have analyzed the microbiome of the small intestine. Here, we examine what is known about the human small intestinal microbiota in terms of community structure and functional properties. We examine temporal dynamics of select bacterial populations in the small intestine, and the effects of dietary carbohydrates and fats on shaping these populations. We then evaluate dysbiosis in the small intestine in several human disease models, including small intestinal bacterial overgrowth, short-bowel syndrome, pouchitis, environmental enteric dysfunction, and irritable bowel syndrome. What is clear is that the bacterial biology, and mechanisms of bacteria-induced pathophysiology, are enormously broad and elegant in the small intestine. Studying the small intestinal microbiota is challenged by rapidly fluctuating environmental conditions in these intestinal segments, as well as the complexity of sample collection and bioinformatic analysis. Because the functionality of the digestive tract is determined primarily by the small intestine, efforts must be made to better characterize this unique and important microbial ecosystem., (Copyright © 2020 The Authors. Published by Elsevier Inc. All rights reserved.)

Short bowel syndrome (SBS) presents an increasing problem in pediatrics. SBS often results from surgical resection of necrotic bowel following necrotizing enterocolitis or treatment of anatomic gastrointestinal defects. SBS is associated with significant morbidity and mortality, and creates substantial burdens for patients, families, and the health system. Recent reports have demonstrated that the fecal microbiome of children with SBS is significantly different from healthy control and severe intestinal microbial imbalances is associated with poor growth. We hypothesized that children with SBS and adverse clinical features such as PN dependent, shorter bowel length and lack of ileocecal valve would demonstrate more gut dysbiosis compare with the SBS non-PN dependent. An improved understanding of SBS pathogenesis would enhance management and potentially suggest new interventions. We studied microbial communities of SBS and control non-SBS patients from the jejunum, obtained endoscopically or by ostomy aspiration, and stool. We enrolled SBS patients who did and did not require parenteral nutrition (PN), as a surrogate marker for the seriousness of their disease. We studied the microbiota using high-throughput DNA sequencing of 16S rRNA genes and statistical analyses. We found that microbial diversity was significantly greater in jejunal aspirate than in stool samples in SBS patients, unlike non-SBS patients; that SBS patients receiving enteral feeds had greater diversity, and that SBS patients on PN and enteral feeds had lower differences in diversity in jejunal vs. stool samples. We found a trend toward increased diversity in patients with an intact ileocecal valve, and found that certain taxa were more abundant in the certain sample types, and in SBS patients vs. non-SBS patients. SBS patients have lower microbial diversity, especially patients with more severe disease, patients requiring PN, and those lacking an ileocecal valve. SBS patients, particularly those with more complex characteristics, exhibit differences in their intestinal microbiota. Particular individual taxa were over- and under-represented in patients with more unfavorable disease. While diminished diversity and alterations in microbiota composition are likely consequences of SBS, future efforts aimed at increasing microbial diversity and interventions targeting specific microbiota characteristics might constitute a testable approach to ameliorate some clinical SBS clinical consequences., Competing Interests: Some authors' institutions may consider pursuing protection for intellectual property related to this paper. This does not alter our adherence to PLoS ONE policies on sharing data and materials.

Fecal microbiota transplantation (FMT) involves the transfer of stool from a healthy individual into the intestinal tract of a diseased recipient. Although used primarily for recurrent Clostridium difficile infection, FMT is increasingly being attempted as an experimental therapy for other illnesses, including metabolic disorders. D-lactic acidosis (D-LA) is a metabolic disorder that may occur in individuals with short bowel syndrome when lactate-producing bacteria in the colon overproduce D-lactate. This results in elevated systemic levels of D-lactate, metabolic acidosis, and encephalopathy. In this study, we report the successful use of FMT for the treatment of recurrent D-LA in a child who was unresponsive to conventional therapies. Importantly, we also present profiles of the enteric microbiota, as well as fecal D-/L-lactic acid metabolites, before and longitudinally after FMT. These data provide valuable insight into the putative mechanisms of D-LA pathogenesis and its treatment.

Children with short bowel syndrome have significant changes to their intestinal microbiota after intestinal loss. The purpose of this article is to understand the potential implications of these changes on gut function, hepatic cholestasis and overall nutrition. Possible therapies to restore the commensal bacterial community in these patients will also be reviewed., (Copyright © 2018. Published by Elsevier Inc.)

Purpose of Review: Short bowel syndrome (SBS) is a rare disease but with many complications due to intestinal failure, parenteral nutrition and underlying disease. A better prevention, comprehension and treatment could improve the outcome of these patients., Recent Findings: Recent studies have been published on acute intestinal failure, first cause of SBS, and gives us strategy to avoid extended intestinal resection and thus SBS. There has been progress in the comprehension of intestinal adaptation, characterized by improvements in intestinal absorption, changes on hormonal secretion, development of a hyperphagia and dysbiosis of the gut microbiota. Hormonal treatment focusing on intestinal rehabilitation by promoting intestinal hyperadaptation has been proposed in patients with SBS, who require parenteral nutrition and intravenous fluids, such as glucagon-like peptide-2 (GLP-2) analog which is now recommended by the latest European Society for Clinical Nutrition and Metabolism Guidelines., Summary: Multimodal treatment of acute meseteric ischemia may avoid intestinal resection and is an effective prevention strategy for SBS. New understandings in intestinal adaptation can help us to optimize this adaptation, including with hormonal therapy. GLP-2 analog is now the treatment of reference in SBS patients with chronic intestinal failure.

The gut microbiota is a crucial actor in human physiology. Many of these effects are mediated by metabolites that are either produced by the microbes or derived from the transformation of environmental or host molecules. Among the array of metabolites at the interface between these microorganisms and the host is the essential aromatic amino acid tryptophan (Trp). In the gut, the three major Trp metabolism pathways leading to serotonin (5-hydroxytryptamine), kynurenine (Kyn), and indole derivatives are under the direct or indirect control of the microbiota. In this review, we gather the most recent advances concerning the central role of Trp metabolism in microbiota-host crosstalk in health and disease. Deciphering the complex equilibrium between these pathways will facilitate a better understanding of the pathogenesis of human diseases and open therapeutic opportunities., (Copyright © 2018 Elsevier Inc. All rights reserved.)

We describe 3 patients with short bowel syndrome who had persistently elevated serum methylmalonic acid (MMA) levels while being treated for vitamin B12 deficiency. Following treatment for presumed small bowel bacterial overgrowth, MMA levels normalized. Among patients with short bowel syndrome, MMA levels may have limited specificity for vitamin B12 deficiency., (Copyright © 2017 Elsevier Inc. All rights reserved.)

Introduction: Intestinal bacterial flora plays a central role in human intestinal health and disease. Short Bowel Syndrome (SBS), a clinical condition deriving from extensive bowel resections, influence intestinal microbiota (IM) composition in order to reach a new metabolic balance. Little is known about IM in adult patients after wide intestinal resections., Material and Methods: Fecal samples from 12 SBS patients and 16 controls were analyzed in their microbial profile by using both culture-dependent method and quantitative Real-Time PCR (qRT-PCR)., Results: The two methods revealed significant lower concentrations of Bacteroidetes (p-value = .02), Firmicutes (p-value = .05), Bifidobacterium (p-value < .01), and Methanobrevibacter Smithii (p-value = .04) in SBS patients than controls., Conclusions: The significantly different fecal microbiome in SBS patients compared with healthy controls could open new perspectives on the care of their intestinal functions., (Copyright © 2016 Elsevier Ltd and European Society for Clinical Nutrition and Metabolism. All rights reserved.)

Background and Aim: Short bowel syndrome (SBS) is a common cause of intestinal failure and can be divided into three types depending on intestinal anatomy. Gut dysbiosis has been observed in pediatric SBS patients and is associated with impaired outcome. Little is known about the changes in gut microbiota of adult SBS patients. Therefore, we aim to characterize the fecal microbiota of adult patients with different types of SBS., Methods: Fifteen fecal samples from healthy controls and adult patients with type II or type III SBS were collected (five in each group). Fecal microbial compositions were determined by high-throughput sequencing, and functional potential was predicted by Phylogenetic Investigation of Communities by Reconstruction of Unobserved States., Results: Bacterial α-diversity significantly decreased in SBS patients and positively correlated to the remaining small bowel length. SBS II patients were enriched with Proteobacteria but deficient in Firmicutes and Bacteroidetes. Whereas Lactobacillus and Prevotella dominated the microbiomes of SBS III patients, commensal bacteria from Lachnospiraceae, Ruminococcaceae, and Bacteroidaceae declined in SBS patients. The parenteral nutrition duration of SBS patients was positively related to the proportion of Enterobacteriaceae but negatively related to Lactobacillus. Functional pathways of citrate cycle and branched-chain and aromatic amino acid biosynthesis were abundant in SBS II patients, while functional profiles of pyrimidine and purine metabolism were dominant in SBS III patients., Conclusions: Short bowel syndrome patients have a marked intestinal dysbiosis with type II SBS characterized by Proteobacteria and type III SBS featured by Lactobacillus, resulting in altered functional profiles of fecal microbiomes., (© 2017 Journal of Gastroenterology and Hepatology Foundation and John Wiley & Sons Australia, Ltd.)

Background: Children with short bowel syndrome (SBS) can vary significantly in their growth trajectory. Recent data have shown that children with SBS possess a unique gut microbiota signature compared with healthy controls. We hypothesized that children with SBS and poor growth would exhibit more severe gut microbiota dysbiosis compared with those with SBS who are growing adequately, despite similar intestinal anatomy., Materials and Methods: Stool samples were collected from children with SBS (n = 8) and healthy controls (n = 3) over 3 months. Gut microbiota populations (16S ribosomal RNA sequencing and metagenomic shotgun sequencing) were compared, including a more in-depth analysis of SBS children exhibiting poor and good growth. Statistical analysis was performed using Mann-Whitney, Kruskal-Wallis, and χ 2 tests as appropriate., Results: Children with SBS had a significant deficiency of the commensal Firmicutes order Clostridiales ( P = .025, Kruskal-Wallis) compared with healthy children. Furthermore, children with SBS and poor growth were deficient in beneficial bacteria known to produce short-chain fatty acids and had expansion of proinflammatory Enterobacteriaceae ( P = .038, Kruskal-Wallis) compared with children with SBS who were growing adequately. Using metabolic function analyses, SBS/poor growth microbiomes were deficient in genes needed for gluconeogenesis but enriched in branched and aromatic amino acid synthesis and citrate cycle pathway genes., Conclusions: Patients with SBS, particularly those with suboptimal growth, have a marked gut dysbiosis characterized by a paucity of beneficial commensal anaerobes, resulting in a deficiency of key metabolic enzymes found in the gut microbiomes of healthy children.

Background: The gut microbiota plays a vital role in modulating the metabolic and immune functions of the intestines. We aimed to analyze the dysbiosis of microbiota in infants with short bowel syndrome (SBS) with different complications., Procedure: We included 26 fecal samples from 18 infants with SBS during parenteral nutrition. The samples were categorized into three groups: asymptomatic, parenteral nutrition-associated liver disease (PNALD), and central line-associated bloodstream infection (CLABSI). Seven healthy infants were enrolled as controls. Fecal microbiota, secretory IgA, calprotectin, bile acids, and short chain fatty acids were detected., Results: The bacterial diversity of the Asymptomatic and Control Groups was significantly higher than that in the PNALD and CLABSI Groups. Proteobacteria was the most pronounced phylum in the PNALD and CLABSI Groups. Decreased acetate was observed in all SBS samples; however, fecal secretory IgA and calprotectin and the proportion of primary and secondary bile acids did not differ from those in healthy controls., Conclusions: Marked alterations of the intestinal microbiota with decreased level of acetate were shown in SBS patients compared with healthy controls. Over-abundance of Proteobacteria (especially Enterobacteriaceae) was found in the samples from the PNALD and CLABSI Groups., Level of Evidence: Prognosis Study, Level I., (Copyright © 2017 Elsevier Inc. All rights reserved.)

Introduction: Antioxidants essential trace elements (TEs), selenium (Se), zinc (Zn) and copper (Cu) are key dietary components and their supplementation in parenteral nutrition (PN) is recommended. However, the frequency of marginal deficiencies and related clinical outcomes remain poorly known in patients receiving long-term PN., Methods and Objectives: We conducted a retrospective observational study whose aim was to determine in a cohort of patients (n = 73) with chronic intestinal failure (CIF) enrolled in a tertiary home PN center and receiving long-term PN with systematic multi-TE supplementation, the prevalence of low serum TEs levels. The goal was also to assess mid-term incidence of serious infection and its associated factors., Results: Among the 73 studied patients, 21.9%, 13.9% and 21.1% had low serum Se (<0.9 μmol/l), Cu (<12.7 μmol/l) and Zn (<12.5 μmol/l) levels, respectively. There was no difference between short bowel syndrome (SBS) and non-SBS patients. 30 patients had at least one of the three serum TEs levels under the cut-off values of deficiency. No specific disease and/or underlying intestinal anatomy were associated with low serum TEs concentration. Cumulative incidence rates of serious infection were 11.1% 95CI[5.7-21.0] and 19.5% 95CI[12.0-30.7] at 6 months and 1 year, respectively. Central venous catheter-related bloodstream infection was the most common infection. Low serum Se was independently associated with a higher risk to develop serious infection (HR 2.65 95CI[1.01-6.97])., Conclusion: Low serum TEs concentration is a frequent condition in patients with CIF even with systematic multi-TE supplementations. Se deficiency exposes to a greater risk of serious infection. This suggests that frequent TEs dosage in this population as well as individually tailored supplementation may be beneficial., (Copyright © 2016 Elsevier Ltd and European Society for Clinical Nutrition and Metabolism. All rights reserved.)

Liver disease is a major source of morbidity and mortality in children with short bowel syndrome (SBS). SBS-associated microbial dysbiosis has recently been implicated in the development of SBS-associated liver disease (SBS-ALD), however the pathological implications of this association have not been explored. In this study high-throughput sequencing of colonic content from the well-validated piglet SBS-ALD model was examined to determine alterations in microbial communities, and concurrent metabolic alterations identified in urine samples via targeted mass spectrometry approaches (GC-MS, LC-MS, FIA-MS) further uncovered impacts of microbial disturbance on metabolic outcomes in SBS-ALD. Multi-variate analyses were performed to elucidate contributing SBS-ALD microbe and metabolite panels and to identify microbe-metabolite interactions. A unique SBS-ALD microbe panel was clearest at the genus level, with discriminating bacteria predominantly from the Firmicutes and Bacteroidetes phyla. The SBS-ALD metabolome included important alterations in the microbial metabolism of amino acids and the mitochondrial metabolism of branched chain amino acids. Correlation analysis defined microbe-metabolite clustering patterns unique to SBS-ALD and identified a metabolite panel that correlates with dysbiosis of the gut microbiome in SBS.

Background and Aim: Short bowel syndrome (SBS) is primarily characterized by malabsorption and malnutrition, resulting from loss of intestinal absorptive area following massive small bowel resection (SBR). Bile acids and the gut microbiota are functionally linked within the gut-liver axis; however, SBS-associated disturbances within the gut-liver axis remain largely unexplored. The aim of this study was to characterize the evolution of bile acid alterations within the gut-liver axis at both short-term and long-term time points and to relate these changes to alterations in colonic bacterial composition., Methods: Four-week-old piglets were assigned to 75% SBR, sham-operation or non-operation control groups. High throughput sequencing was employed to determine bacterial abundance in colonic content and ultra-performance liquid chromatography used to determine the bile acid concentration of gall bladder, portal serum, and fecal samples., Results: Bile acid complexity and relative abundance are altered in the SBS piglet model at two weeks post-SBR, and these changes persisted at six weeks post-SBR. Our examination of the microbial profile revealed an early and persistent loss in bacteria belonging to the Clostridiales order., Conclusions: This study provides evidence of an early and persistent disturbance of the bile acid profile throughout the entero-hepatic circulation with an increase in the proportion of primary bile acids and a decrease in secondary bile acids following SBR. These changes were associated with a loss of bacteria belonging to the Clostridiales order consistent with a disturbance in the bile-microbial axis following SBR., (© 2016 Journal of Gastroenterology and Hepatology Foundation and John Wiley & Sons Australia, Ltd.)

Background: Intestinal failure-associated liver disease causes significant mortality in patients with short bowel syndrome. Steatosis, a major component of intestinal failure-associated liver disease has been shown to persist even after weaning from parenteral nutrition. We sought to determine whether steatosis occurs in our murine model of short bowel syndrome and whether steatosis was affected by manipulation of the intestinal microbiome., Methods: Male C57BL6 mice underwent 50% small bowel resection and orogastric gavage with vancomycin or vehicle for 10 weeks. DNA was extracted from stool samples then sequenced using 16s rRNA. Liver lipid content was analyzed. Bile acids were measured in liver and stool., Results: Compared with unoperated mice, small bowel resection resulted in significant changes in the fecal microbiome and was associated with a >25-fold increase in steatosis. Oral vancomycin profoundly altered the gut microbiome and was associated with a 15-fold reduction in hepatic lipid content after resection. There was a 17-fold reduction in fecal secondary bile acids after vancomycin treatment., Conclusion: Massive small bowel resection in mice is associated with development of steatosis and prevented by oral vancomycin. These findings implicate a critical role for gut bacteria in intestinal failure-associated liver disease pathogenesis and illuminate a novel, operative model for future investigation into this important morbidity., (Copyright © 2016 Elsevier Inc. All rights reserved.)

Background: Changes in the intestinal microbiome of patients with short bowel syndrome (SBS) are thought to significantly affect clinical outcome. These changes may not only delay enteral diet advancement but may also predispose patients to bacterial translocation, bacteremia, and liver disease. Patients with SBS are thought to be more susceptible to changes in gut microbial communities due to intestinal dysmotility and/or lack of anatomic safeguards such as the ileocecal valve., Materials and Methods: We analyzed the bacterial composition of 21 fecal specimens from 9 children with SBS and 8 healthy children ages 4 months to 8 years by 16S ribosomal RNA gene sequencing. The sequences were quality filtered and analyzed using QIIME, the Ribosomal Database Project Classifier, and the randomForest supervised learning algorithm., Results: The fecal microbiome of patients with SBS is different from that of healthy controls. Stool from patients with SBS had a significantly greater abundance of the bacterial classes Gammaproteobacteria and Bacilli. Stool from patients with SBS who experienced increased stool frequency tended to have increased abundance of Lactobacillus (P = .057) and decreased abundance of Ruminococcus., Conclusion: This study shows that the fecal microbiome of patients with SBS is significantly different from that of healthy controls when analyzed by 16S metagenomics. Differences in the composition and function of gut microbiomes in children with SBS may affect bowel physiology, and these findings may provide new opportunities for intestinal rehabilitation and clinical management., (© 2015 American Society for Parenteral and Enteral Nutrition.)

Background: Central line-associated bloodstream infections (CLABSIs) pose a significant challenge in the lives of patients with intestinal failure (IF). We hypothesized that plasma immunoglobulins against flagellin (FLiC) and lipopolysaccharide (LPS) would be able to differentiate CLABSIs from nonbacterial febrile episodes and that levels would increase with infection and decline following appropriate antibiotic treatment., Materials and Methods: Patients with IF, due to short bowel syndrome, between the ages of 3 months and 4 years of age, were recruited at Cincinnati Children's Hospital Medical Center. Anti-FLiC and anti-LPS plasma antibody levels were measured in 13 children with IF at baseline, during febrile events, and also following treatment with antibiotics. These were also measured in 11 healthy children without IF who were recruited as controls., Results: Plasma anti-FLiC IgA levels increased during febrile episodes in all patients with IF (baseline mean of 1.10 vs febrile episode mean of 1.32 optical density units, respectively; P = .046). Neither plasma anti-FLiC nor anti-LPS IgA or IgG levels distinguished CLABSI from nonbacterial febrile episodes compared with baseline levels. Compared with controls, patients with IF had significantly higher plasma levels of anti-FLiC and anti-LPS IgA at baseline., Conclusion: Plasma anti-FLiC IgA antibody levels rise during febrile episodes but do not differentiate between nonbacterial febrile illnesses and CLABSIs in pediatric IF. However, the upregulation of these antibodies in IF suggests the baseline systemic presence of Gram-negative bacterial products., (© 2014 American Society for Parenteral and Enteral Nutrition.)

Purpose: The enteric microbiome is known to play a major role in healthy gut homeostasis and several disease states. It may also contribute to both the intestinal recovery and complications that occur in patients with short bowel syndrome. The extent and nature of alterations to the gut microbiota following intestinal resection, however, are not well studied in a controlled setting. The purpose of this investigation is to characterize the effects of massive small bowel resection on the murine enteric microflora., Methods: Wild-type C57BL6 mice, following a week of acclamation to a liquid rodent diet, underwent either 50% proximal small bowel resection (SBR) or a sham operation. Mice were sacrificed, and enteric contents from the small bowel, cecum, and stool were harvested at 7 and 90 days post-operatively. DNA was isolated, and the V3-V5 regions of the 16s rRNA gene amplified and pyrosequenced on a Roche 454 platform. Sequences were clustered into operation taxonomic units and classified. Communities were then analyzed for diversity and phylogenic composition., Results: In the long-term group, the microbes inhabiting the ileum of mice undergoing SBR and sham operation differed significantly at the genus level (p < 0.001). Small bowel contents collected before and after SBR also differed significantly (p = 0.006). This was driven by an increase in Lactobacillus and decrease in Enterobacteriaceae species in mice undergoing SBR. No difference was seen in the long-term stool or in stool, cecal, or ileal contents in the short-term. No difference in microbial community diversity was found in any group., Conclusion: Bowel resection induces long-term changes in the microbial community of the murine ileum, but not at more distal sites of the gastrointestinal tract. The increase in Lactobacillus encountered small bowel of resected mice correlates with limited previous studies. These changes may reflect an adaptive response of the microbiota to maximize energy extraction, but further studies are needed to establish the role played by this altered community.

Background & Aims: Despite the mortality associated with liver disease observed in patients with short bowel syndrome (SBS), mechanisms underlying the development of SBS-associated liver disease (SBS-ALD) are poorly understood. This study examines the impact of bacterially-mediated bile acid (BA) dysmetabolism on farnesoid X receptor (FXR) signalling pathways and clinical outcome in a piglet model of SBS-ALD., Methods: 4-week old piglets underwent 75% small bowel resection (SBR) or sham operation. Liver histology and hepatic inflammatory gene expression were examined. Abundance of BA biotransforming bacteria was determined and metabolomic studies detailed the alterations in BA composition of stool, portal serum and bile samples. Gene expression of intestinal and hepatic FXR target genes and small heterodimer partner (SHP) transrepression targets were assessed., Results: Histological evidence of SBS-ALD included liver bile duct proliferation, hepatocyte ballooning and fibrosis. Inflammatory gene expression was increased. Microbiota changes included a 10-fold decrease in Clostridium and a two-fold decrease in Bacteroides in SBS-ALD piglets. BA composition was altered and reflected a primary BA dominant composition. Intestinal and hepatic regulation of BA synthesis was characterised by a blunted intestinal FXR activation response and a failure of SHP to repress key hepatic targets., Conclusions: We propose a pathological scenario in which microbial dysbiosis following SBR results in significant BA dysmetabolism and consequent outcomes including steatorrhoea, persistent diarrhoea and liver damage. Furthermore alterations in BA composition may have contributed to the observed disturbance in FXR-mediated signalling pathways. These findings provide an insight into the complex mechanisms mediating the development of liver disease in patients with SBS., (Crown Copyright © 2014. Published by Elsevier B.V. All rights reserved.)

Previous studies have shown that bovine lactoferrin (bLF) exerts antibacterial, immune-modulating and anti-inflammatory effects. The present study aimed to investigate the effect of enteral bLF supplementation on intestinal adaptation and barrier function in a rat model of short bowel syndrome (SBS). Male Sprague-Dawley rats aged 4 weeks were randomised into three groups (n 10 per group): Sham group (rats submitted to bowel transection and reanastomosis); SBS group (rats submitted to 80 % small-bowel resection); SBS-bLF group (rats submitted to 80 % small-bowel resection plus treatment with bLF (0·5 g/kg per d) by oral administration from day 2 to day 20). Despite similar food intake, both the SBS and SBS-bLF groups exhibited significantly lower body weight gain, but increased villus height and crypt depth and a higher intestinal epithelial cell proliferation index (P< 0·05) when compared with the Sham group. Compared with that in the SBS group, in the SBS-bLF group, bacterial translocation to regional organs was low and intestinal permeability was significantly reduced. The SBS-bLF group also had increased secretory IgA (sIgA) concentrations in ileal contents (29·9 (23·8-33·0) ng/ml), when compared with the other two groups having similar sIgA concentrations (17·5 (12·6-29·1) and 19·3 (11·5-27·0) ng/ml, respectively). The relative expression levels of two tight junction (TJ) proteins, occludin and claudin-4, in the SBS-bLF group were significantly higher than those in the SBS group (P< 0·05), but did not exhibit any significant differences when compared with those in the Sham group. In conclusion, enteral bLF supplementation up-regulates small-bowel sIgA concentrations and TJ protein expression and reduces intestinal permeability and could thus support intestinal barrier integrity and protect against bacterial infections in SBS.

Background and Objectives: Following small bowel resection (SBR), the luminal environment is altered, which contributes to clinical manifestations of short bowel syndrome (SBS) including malabsorption, mucosal inflammation and bacterial overgrowth. However, the impact of SBR on the colon has not been well-defined. The aims of this study were to characterize the colonic microbiota following SBR and to assess the impact of SBR on mucosal inflammation in the colon., Results: Analysis of the colonic microbiota demonstrated that there was a significant level of dysbiosis both two and six weeks post-SBR, particularly in the phylum Firmicutes, coupled with a decrease in overall bacterial diversity in the colon. This decrease in diversity was associated with an increase in colonic inflammation six weeks post-surgery., Methods: Female (4-week old) piglets (5-6/group) received a 75% SBR, a transection (sham) or no surgery. Compositional analysis of the colonic microbiota was performed by high-throughput sequencing, two- and six-weeks post-surgery. The gene expression of the pro-inflammatory cytokines interleukin (IL)-1β, IL-6, IL-8, IL-18 and tumor necrosis factor (TNF)-α in the colonic mucosa was assessed by qRT-PCR and the number of macrophages and percentage inducible nitric oxide synthase (iNOS) staining in the colonic epithelium were quantified by immunohistochemistry., Conclusions: SBR significantly decreased the diversity of the colonic microbiota and this was associated with an increase in colonic mucosal inflammation. This study supports the hypothesis that SBR has a significant impact on the colon and that this may play an important role in defining clinical outcome.

Our objective was to understand the functional link between the composition of faecal microbiota and the clinical characteristics of adults with short bowel syndrome (SBS). Sixteen patients suffering from type II SBS were included in the study. They displayed a total oral intake of 2661±1005 Kcal/day with superior sugar absorption (83±12%) than protein (42±13%) or fat (39±26%). These patients displayed a marked dysbiosis in faecal microbiota, with a predominance of Lactobacillus/Leuconostoc group, while Clostridium and Bacteroides were under-represented. Each patient exhibited a diverse lactic acid bacteria composition (L. delbrueckii subsp. bulgaricus, L. crispatus, L. gasseri, L. johnsonii, L. reuteri, L. mucosae), displaying specific D and L-lactate production profiles in vitro. Of 16 patients, 9/16 (56%) accumulated lactates in their faecal samples, from 2 to 110 mM of D-lactate and from 2 to 80 mM of L-lactate. The presence of lactates in faeces (56% patients) was used to define the Lactate-accumulator group (LA), while absence of faecal lactates (44% patients) defines the Non lactate-accumulator group (NLA). The LA group had a lower plasma HCO3(-) concentration (17.1±2.8 mM) than the NLA group (22.8±4.6 mM), indicating that LA and NLA groups are clinically relevant sub-types. Two patients, belonging to the LA group and who particularly accumulated faecal D-lactate, were at risk of D-encephalopathic reactions. Furthermore, all patients of the NLA group and those accumulating preferentially L isoform in the LA group had never developed D-acidosis. The D/L faecal lactate ratio seems to be the most relevant index for a higher D-encephalopathy risk, rather than D- and L-lactate faecal concentrations per se. Testing criteria that take into account HCO3(-) value, total faecal lactate and the faecal D/L lactate ratio may become useful tools for identifying SBS patients at risk for D-encephalopathy.

Purpose: To characterize of the intestinal microbiota of patients with short bowel syndrome (SBS) admitted to the Metabolic Unit of a University Hospital., Methods: Fecal samples were evaluated, and biochemical tests were conducted only in the case of SBS patients. The nutritional status was assessed via anthropometric measurements and evaluation of food intake by means of a food questionnaire. The pathogenic strains were detected with the aid of cultures and specific biochemical tests in aerobic medium, for determination of species belonging to the Family enterobacteriaceae. Anti-sera were applied to each isolated E. coli strain, for determination of their possible pathogenicity. Molecular methodology was employed for establishment of the intestinal bacterial microbiota profile, Results: A lower amount of microorganisms of the family enterobacteriaceae per gram of stool was observed in the case of patients with SBS. However, molecular analysis showed maintenance of the bacterial species ratio, which is equivalent to a healthy intestinal microbiota., Conclusion: Despite the massive removal of the small bowel, frequent use of antibiotics, immune system depression, presence of non-digested food in the gastrointestinal tract, and accelerated intestinal transit, the ratio between intestinal bacterial species remain similar to normality.

Background: Children with intestinal failure (IF) are at risk for small bowel bacterial overgrowth (SBBO) because of anatomical and other factors. We sought to identify risk factors for SBBO confirmed by quantitative duodenal culture., Methods: A single-center retrospective record review of children who had undergone endoscopic evaluation for SBBO (defined as bacterial growth in duodenal fluid of >10(5) colony-forming unit per mL) was performed., Results: We reviewed 57 children with median (25th-75th percentile) age 5.0 (2.0-9.2) years. Diagnoses included motility disorders (28%), necrotizing enterocolitis (16%), atresias (16%), gastroschisis (14%), and Hirschsprung disease (10.5%). Forty patients (70%) had confirmed SBBO. Univariate analysis showed no significant differences between patients with and without SBBO for the following variables: age, sex, diagnosis, presence of ileocecal valve, and antacid use. Patients receiving parenteral nutrition (PN) were more likely to have SBBO (70% vs 35%, P = .02). Multiple logistic regression analysis confirmed that PN administration was independently associated with SBBO (adjusted odds ratio, 5.1; adjusted 95% confidence interval, 1.4-18.3; P = .01). SBBO was not related to subsequent risk of catheter-related bloodstream infection (CRBSI)., Conclusion: SBBO is strongly and independently associated with PN use. Larger prospective cohorts and more systematic sampling techniques are needed to better determine the relationship between SBBO and gastrointestinal function., (Copyright © 2012 Elsevier Inc. All rights reserved.)

Background: After massive bowel resection, bacterial overgrowth is frequent and favors the occurrence of Gram-negative intestinal bacterial translocation (BT). Probiotics have been recommended in several diseases and may also have beneficial effects on BT. Conversely, polymerase chain reaction (PCR) technique has shown better sensitivity than conventional methods in bacterial detection and has not been investigated in experimental models of short bowel syndrome and BT., Objective: To test the hypothesis that Bifidobacterium lactis (BL) administration decreases Escherichia coli bacterial translocation (ECBT) in experimental short bowel syndrome and to confirm the better sensitivity of PCR technique to detect ECBT., Methods: Forty-eight adult Wistar rats, orally fed with standard rat chow and tap water ad libitum, were maintained in individual metabolic cages for 10 days and divided into three groups: Control group (n = 15): non-manipulated animals. RES group (n = 15): 80% gut resection. 1 ml of sterile water was administered daily after orogastric intubation. RES-PRO group (n = 18): same resection as RES group and daily administration of 7.8 × 10(9) BL (CFU). At the end of the study, portal blood, peripheral blood and mesenteric lymph node (MLN) samples were recovered and cultured. Also, genomic DNA from E. coli was detected by PCR technique., Results: In conventional culture there was no ECBT in control animals whereas 73% of RES and 33% of RES-PRO animals showed it. PCR detected ECBT in 47, 87 and 33%, respectively, showing higher sensitivity.

Background: Home parenteral nutrition (HPN) is lifesaving for children with intestinal failure. Catheter-associated bloodstream infections (CA-BSI) are common in hospitalized patients receiving parenteral nutrition (PN), but data evaluating CA-BSI in children receiving HPN are limited., Objective: To determine the incidence and characteristics of CA-BSI in children receiving HPN., Methods: Medical records of 44 children receiving HPN during a 3-year period were reviewed. End points were CA-BSI during the initial 6 months after discharge. CA-BSI was defined as isolation of pathogens from blood requiring antimicrobial therapy., Results: The primary indication for HPN was short bowel syndrome (46%), and 59 BSI were documented during the initial 6 months of HPN in 29 (66%) children. Of CA-BSI, polymicrobial infections accounted for 52%; gram-positive, 29%; gram-negative, 17%; and fungal, 2%. CA-BSI incidence per 1000 catheter-days was highest during the first month posthospital discharge (72 episodes; 95% confidence interval [CI], 45.4-109.6). CA-BSI incidence density ratio for children receiving HPN for >90 days compared with those receiving HPN for <30 days was 2.2 (P < .05). Logistic regression revealed that Medicaid insurance and age <1 year were associated with increased risk for CA-BSI (odds ratio [OR], 4.4 [95% CI, 1.13-16.99] and 6.6 [1.50-28.49], respectively; P < .05)., Conclusions: The incidence of CA-BSI in children receiving HPN is highest during the first month posthospital discharge. Strategies to address care in the immediate posthospital discharge period may reduce the burden of infectious complications of HPN.

The mechanism of impaired gut barrier function in patients with short bowel syndrome (SBS) is poorly understood and includes decreased intestinal motility leading to bacterial overgrowth, a reduction in gut-associated lymphoid tissue following the loss of intestinal length, inhibition of mucosal immunity of the small intestine by intravenous total parental nutrition, and changes in intestinal permeability to macromolecules. Novel therapeutic strategies (i.e. nutritive and surgical) have been introduced in order to prevent the establishment or improve the outcome of this prevalent disease. Pre- and probiotics as a nutritive supplement are already known to be very active in the intestinal tract (mainly in the colon) by maintaining a healthy gut microflora and influencing metabolic, trophic and protective mechanisms, such as the production of SCFA which influence epithelial cell metabolism, turnover and apoptosis. Probiotics have been recommended for patients suffering from SBS in order to decrease bacterial overgrowth and prevent bacterial translocation, two major mechanisms in the pathogenesis of SBS. The present review discusses the research available in the international literature, clinical and experimental, regarding probiotic supplementation for this complicated group of patients based on the clinical spectrum and pathophysiological aspects of the syndrome. The clinical data that were collected for the purposes of the present review suggest that it is difficult to correctly characterise probiotics as a preventive or therapeutic measure. It is very challenging after all to examine the relationship of the bacterial flora, the intestinal barrier and the probiotics as, according to the latest knowledge, demonstrate an interesting interaction.

Short bowel syndrome (SBS) is the main cause of intestinal failure especially in children. The colon is a crucial partner for small intestine adaptation and function in patients who have undergone extensive small bowel resection. However, SBS predisposes the patient to small intestine bacterial overgrowth (SIBO), explaining its high prevalence in patients with this disorder. SIBO may significantly compromise digestive and absorptive functions and may delay or prevent weaning from total parenteral nutrition (TPN). Moreover, SIBO may be one of the causes of intestinal failure-associated liver disease, requiring liver transplantation in some cases. Traditional tests for assessing SIBO may be unreliable in SBS patients. Management of SIBO with antibiotic therapy as a first-line approach remains a matter of debate, while other approaches, including probiotics, offer potential based on experimental evidence, though only few data from human studies are available., (Copyright © 2010 Elsevier Masson SAS. All rights reserved.)

Short bowel syndrome (SBS) is observed in Humans after a large resection of gut. Since the remnant colon and its associated microbiota play a major role in the outcome of patients with SBS, we studied the overall qualitative and quantitative microbiota composition of SBS adult patients compared to controls. The population was composed of 11 SBS type II patients (with a jejuno-colonic anastomosis) and 8 controls without intestinal pathology. SBS patients had 38 +/- 30 cm remnant small bowel length and 66 +/- 19% of residual colon. The repartition of proteins, lipids, carbohydrates and fibres was expressed as % of total oral intake in patients and controls. The microbiota was profiled from stool and biopsy samples with temporal temperature gradient gel electrophoresis and quantitative PCR. We show here that microbiota of SBS patients is unbalanced with a high prevalence of Lactobacillus along with a sub-dominant presence and poor diversity of Clostridium leptum, Clostridium coccoides and Bacteroidetes. In addition, Lactobacillus mucosae was detected within the fecal and mucosa-associated microbiota of SBS patients, whereas it remained undetectable in controls. Thus, in SBS the microbial composition was deeply altered in fecal and mucosal samples, with a shift between dominant and sub-dominant microbial groups and the prevalence of L. mucosae., (Copyright 2010 Elsevier Masson SAS. All rights reserved.)

Background: The intestinal wall integrity is central to the barrier function and depends on the balance of proliferation/apoptosis. Short bowel (SB) or Parenteral Nutrition (PN) induce high bacterial translocation (BT) probably by the intestinal barrier bug. Probiotics or minimal enteral nutrition (MEN) have reduced BT in animal models., Objective: Determine in two BT animal models (SB or PN) the effect of MEN or probiotics on proliferation and apoptosis rates of the intestinal wall., Methods: Seventy-one Wistar rats, divided into 4 groups: 1) PN (N = 23): parenteral nutrition; 2) PNMEN (N = 16): PN + MEN (2.9 g/100 g/day standard diet); 3) RES (N = 15): 80% bowel resection and standard oral diet; 4) RESPROB (N = 17): RES + probiotics (7 X 10(9) CFU Bifidobacterium lactis). After 10 days in metabolic cages, mesenteryc lymph nodes, portal blood and peripheral blood were cultured. By immunohistochemistry, proliferation and apoptosis index were calculated as well as the proliferation-apoptosis rate., Results: BT: decreased in PNMEN (45%) and RESPROB groups (35%) versus PN (65%) and RES (67%) groups (p<0.05). Proliferation index: was better in PNMEN (12,07) and RESPROB (13,93) groups than PN (7,45) and RES (5,54) groups. (p

Short bowel syndrome (SBS) is associated with gut barrier dysfunction. We examined effects of dietary glutamine (GLN) or oral antibiotics (ABX) on indexes of gut barrier function in a rat model of SBS. Adult rats underwent a 60% distal small bowel + proximal colonic resection (RX) or bowel transection (TX; control). Rats were pair fed diets with or without l-GLN for 20 days after operation. Oral ABX (neomycin, metronidazole, and polymyxin B) were given in some RX rats fed control diet. Stool secretory immunoglobulin A (sIgA) was measured serially. On day 21, mesenteric lymph nodes (MLN) were cultured for gram-negative bacteria. IgA-positive plasma cells in jejunum, stool levels of flagellin- and lipopolysaccharide (LPS)-specific sIgA, and serum total, anti-flagellin- and anti-LPS IgG levels were determined. RX caused gram-negative bacterial translocation to MLN, increased serum total and anti-LPS IgG and increased stool total sIgA. After RX, dietary GLN tended to blunt bacterial translocation to MLN (-29%, P = NS) and significantly decreased anti-LPS IgG levels in serum, increased both stool and jejunal mucosal sIgA and increased stool anti-LPS-specific IgA. Oral ABX eliminated RX-induced bacterial translocation, significantly decreased total and anti-LPS IgG levels in serum, significantly decreased stool total IgA and increased stool LPS-specific IgA. Partial small bowel-colonic resection in rats is associated with gram-negative bacterial translocation from the gut and a concomitant adaptive immune response to LPS. These indexes of gut barrier dysfunction are ameliorated or blunted by administration of dietary GLN or oral ABX, respectively. Dietary GLN upregulates small bowel sIgA in this model.

The gastrointestinal tract possesses a huge epithelial surface area and performs many different tasks. Amongst them are the digestive and absorptive functions. Disorders of intestinal absorption and secretion comprise a variety of different diseases, e.g. coeliac disease, lactase deficiency or Whipple's disease. In principle, impaired small intestinal function can occur with or without morphological alterations of the intestinal mucosa. Therefore, in the work up of a malabsorptive syndrome an early small intestinal biopsy is encouraged in conjunction with breath tests and stool analysis to guide further management. In addition, there is an array of functional tests, the clinical availability of which becomes more and more limited. In any case, early diagnosis of the underlying pathophysiology is most important, in order to initiate proper therapy. In this chapter, diagnostic procedure of malabsorption is discussed with special attention to specific disease like coeliac disease, Whipple's disease, giardiasis and short bowel syndrome. Furthermore, bacterial overgrowth, carbohydrate malabsorption and specific nutrient malabsorption (e.g. for iron or vitamins) and protein-losing enteropathy are presented with obligatory and optional tests as used in the clinical setting.

Background: Bacterial overgrowth occuring after massive bowel resection, facilitates Gram-negative intestinal Bacterial Translocation (TB). Probiotic agents might have beneficial effects on TB. On the other hand, polymerase chain-reaction (PCR) has better sensitivity than conventional methods for bacterial detection and has not been investigated in experimental models of short bowel syndrome and TB., Objective: To test the hypothesis that the administration of Bifidobacterium lactis (BL) decreases Escherichia coli Bacterial Translocation (ECTB) in experimental short bowel syndrome and to confirm the better sensitivity of PCR technique to detect ECTB., Methods: Adult Wistar rats, orally fed with standard rat chow and tap water "ad libitum", were maintained in individual metabolic cages for ten days and divided into three groups: Control (n = 15): non-manipulated animals. RES (n = 15): 80% gut resection. Daily administration 1 ml of sterile water, after orogastric intubation. RES-PRO (n = 18): same resection and daily administration of 7.8 x10(9) Bifidobacterium lactis Colony Forming Units (CFU). At the end of the experiment, mesenteric lymph nodes (MLN), and both peripheral and portal blood samples were recovered and cultured by standard procedures. Also, genomic DNA from E. coli was detected by PCR technique., Results: By conventional cultures ECTB was detected in 0% in the control group, 73% in the RES group and 33% in the RES-PRO group. PCR technique detected ECTB in 47% of the control group, 87% of the RES group and 33% of RES-PRO group, showing higher sensitivity. By both methods, animals receiving BL (RES-PRO group) showed less ECTB. By conventional culture, the relative risk (RR) was 0.45 (95% CI 0,22-0,79) and the number needed to treat (NNT) was 3 (95% CI 0-11). By PCR technique, the RR was 0.38 (95% CI 0.19-0.76), and the NNT 2 (95% CI 0-4)., Conclusions: 1) Administration of Bifidobacterium lactis reduces the incidence of ECTB. 2) PCR technique is a more sensitive method for ECTB detection.