Intestinal microbial and metabolite profile in infants with small bowel stomas after bowel resection.

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.

Influence of the bile acid/microbiota axis in ileal surgery: a systematic review.

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.

Impact of hepatocyte growth factor on the colonic morphology and gut microbiome in short bowel syndrome rat model.

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.

Therapeutic potential of an intestinotrophic hormone, glucagon-like peptide 2, for treatment of type 2 short bowel syndrome rats with intestinal bacterial and fungal dysbiosis.

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.

Broad-spectrum antibiotics alter the microbiome, increase intestinal fxr, and decrease hepatic steatosis in zebrafish short bowel syndrome.

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 (tlr4), 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.

The Impact of Lactobacillus Probiotics on the Gut Microbiota in Children With Short Bowel Syndrome.

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.

Severe Intestinal Dysbiosis in Rat Models of Short Bowel Syndrome with Ileocecal Resection.

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.

Is Serum Methylmalonic Acid a Reliable Biomarker of Vitamin B12 Status in Children with Short Bowel Syndrome: A Case Series.

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.

What's new in short bowel syndrome?

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.

Intestinal Microbial and Metabolic Alterations Following Successful Fecal Microbiota Transplant for D-Lactic Acidosis.

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.

Fecal microbiota signatures of adult patients with different types of short bowel syndrome.

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.

Short bowel syndrome (SBS)-associated alterations within the gut-liver axis evolve early and persist long-term in the piglet model of short bowel syndrome.

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.

Altered FXR signalling is associated with bile acid dysmetabolism in short bowel syndrome-associated liver disease.

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.

Enteral supplementation of bovine lactoferrin improves gut barrier function in rats after massive bowel resection.

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.

The gut microbiota in adults with chronic intestinal failure.

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.

Does Microbiome Matter in Chronic Intestinal Failure Due to Type 1 Short Bowel Syndrome in Adults?

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.

Gut microbiota and intestinal rehabilitation: a prospective childhood cohort longitudinal study of short bowel syndrome (the MIRACLS study): study protocol.

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.

Fecal microbiota transplantation in a rodent model of short bowel syndrome: A therapeutic approach?

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 ß-diversity were significantly different from Sham. The FMT altered microbiota composition and α- and ß-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.

Bacterial overgrowth assessment and treatment among pediatric intestinal rehabilitation and nutrition support providers: An international survey of clinical practice patterns.

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.

Potential benefits of pro- and prebiotics on intestinal mucosal immunity and intestinal barrier in short bowel syndrome.

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.