RESUMO
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.
Assuntos
Fezes , Microbioma Gastrointestinal , Síndrome do Intestino Curto , Humanos , Síndrome do Intestino Curto/microbiologia , Masculino , Feminino , Pessoa de Meia-Idade , Fezes/microbiologia , Adulto , Compostos Orgânicos Voláteis/análise , Doença Crônica , Idoso , Ácidos Graxos Voláteis/análise , Ácidos Graxos Voláteis/metabolismo , Hiperfagia , Lactobacillus/isolamento & purificação , Enteropatias/microbiologiaRESUMO
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.
Assuntos
Colo , Modelos Animais de Doenças , Microbioma Gastrointestinal , Fator de Crescimento de Hepatócito , Ratos Sprague-Dawley , Síndrome do Intestino Curto , Animais , Ratos , Fator de Crescimento de Hepatócito/metabolismo , Fator de Crescimento de Hepatócito/genética , Microbioma Gastrointestinal/efeitos dos fármacos , Colo/microbiologia , Colo/patologia , Síndrome do Intestino Curto/metabolismo , Síndrome do Intestino Curto/microbiologia , Masculino , Receptor 4 Toll-Like/metabolismo , Receptor 4 Toll-Like/genética , Junções Íntimas/efeitos dos fármacos , Junções Íntimas/metabolismo , Claudina-1/metabolismo , Claudina-1/genéticaRESUMO
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.
Assuntos
Fezes , Microbioma Gastrointestinal , Síndrome do Intestino Curto , Humanos , Masculino , Feminino , Estudos Transversais , Pessoa de Meia-Idade , Fezes/microbiologia , Adulto , Síndrome do Intestino Curto/microbiologia , Síndrome do Intestino Curto/fisiopatologia , Doença Crônica , Idoso , Insuficiência Intestinal/microbiologia , RNA Ribossômico 16S/genéticaRESUMO
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.
Assuntos
Ácidos e Sais Biliares , Fezes , Microbioma Gastrointestinal , Íleo , Doenças Inflamatórias Intestinais , Humanos , Ácidos e Sais Biliares/metabolismo , Microbioma Gastrointestinal/fisiologia , Íleo/cirurgia , Íleo/microbiologia , Fezes/microbiologia , Doenças Inflamatórias Intestinais/cirurgia , Doenças Inflamatórias Intestinais/microbiologia , Síndrome do Intestino Curto/cirurgia , Síndrome do Intestino Curto/microbiologia , Síndrome do Intestino Curto/metabolismo , Feminino , Masculino , Adulto , Pessoa de Meia-IdadeRESUMO
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.
Assuntos
Síndrome do Intestino Curto , Ratos , Animais , Síndrome do Intestino Curto/terapia , Síndrome do Intestino Curto/microbiologia , Síndrome do Intestino Curto/patologia , Roedores , Transplante de Microbiota Fecal , Mucosa Intestinal/patologia , JejunoRESUMO
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.
Assuntos
Infecções Bacterianas , Síndrome do Intestino Curto , Humanos , Criança , Intestino Delgado/microbiologia , Padrões de Prática Médica , Síndrome do Intestino Curto/microbiologia , Antibacterianos/uso terapêutico , Inquéritos e QuestionáriosRESUMO
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.
Assuntos
Antibacterianos/uso terapêutico , Disbiose/tratamento farmacológico , Disbiose/etiologia , Microbioma Gastrointestinal/efeitos dos fármacos , Sepse/tratamento farmacológico , Sepse/etiologia , Síndrome do Intestino Curto/complicações , Adolescente , Criança , Pré-Escolar , Estudos de Coortes , Disbiose/microbiologia , Feminino , Humanos , Masculino , Missouri , Síndrome do Intestino Curto/microbiologiaRESUMO
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.
Assuntos
Microbioma Gastrointestinal/efeitos dos fármacos , Peptídeo 2 Semelhante ao Glucagon/farmacologia , Intestinos/microbiologia , Síndrome do Intestino Curto/patologia , Actinobacteria/genética , Actinobacteria/isolamento & purificação , Animais , Colo/cirurgia , Colostomia , Análise Discriminante , Modelos Animais de Doenças , Disbiose , Fungos/genética , Fungos/isolamento & purificação , Peptídeo 2 Semelhante ao Glucagon/uso terapêutico , Análise dos Mínimos Quadrados , Masculino , Análise de Componente Principal , RNA Ribossômico 16S/análise , RNA Ribossômico 16S/metabolismo , Ratos , Ratos Sprague-Dawley , Síndrome do Intestino Curto/tratamento farmacológico , Síndrome do Intestino Curto/microbiologiaRESUMO
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.
Assuntos
Antibacterianos/farmacologia , Fígado Gorduroso/prevenção & controle , Receptores Citoplasmáticos e Nucleares/metabolismo , Síndrome do Intestino Curto/microbiologia , Animais , Peixe-ZebraRESUMO
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.
Assuntos
Microbioma Gastrointestinal , Lacticaseibacillus rhamnosus , Lactobacillus johnsonii , Probióticos , Síndrome do Intestino Curto/terapia , Criança , Desenvolvimento Infantil , Pré-Escolar , Feminino , Humanos , Lactente , Masculino , Estudos Prospectivos , Síndrome do Intestino Curto/microbiologiaRESUMO
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 (nâ¯=â¯41) were collected from 15 SBS infants (<2â¯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.
Assuntos
Fezes/microbiologia , Intestino Delgado/microbiologia , Síndrome do Intestino Curto/microbiologia , Pré-Escolar , Estudos de Coortes , Colo/microbiologia , Feminino , Microbioma Gastrointestinal , Humanos , Lactente , Masculino , Estudos Prospectivos , RNA Ribossômico 16SRESUMO
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.
Assuntos
Disbiose/microbiologia , Comportamento Alimentar/fisiologia , Microbioma Gastrointestinal/fisiologia , Mucosa Intestinal/microbiologia , Intestino Delgado/microbiologia , Animais , Síndrome da Alça Cega/microbiologia , Síndrome da Alça Cega/fisiopatologia , Carboidratos da Dieta/administração & dosagem , Gorduras na Dieta/administração & dosagem , Modelos Animais de Doenças , Disbiose/complicações , Disbiose/fisiopatologia , Humanos , Síndrome do Intestino Irritável/microbiologia , Síndrome do Intestino Irritável/fisiopatologia , Pouchite/microbiologia , Pouchite/fisiopatologia , Síndrome do Intestino Curto/microbiologia , Síndrome do Intestino Curto/fisiopatologiaRESUMO
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.
Assuntos
Bactérias/classificação , Microbioma Gastrointestinal , Metaboloma , Síndrome do Intestino Curto/microbiologia , Ácidos e Sais Biliares/análise , Disbiose , Fezes/microbiologia , Humanos , Nutrição Parenteral , Compostos Orgânicos Voláteis/análiseRESUMO
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.
Assuntos
Disbiose/microbiologia , Microbioma Gastrointestinal/genética , Síndrome do Intestino Curto/microbiologia , Anastomose Cirúrgica , Animais , Ceco/cirurgia , Clostridiales , Colo/microbiologia , Colo/cirurgia , Disbiose/etiologia , Disbiose/metabolismo , Microbioma Gastrointestinal/fisiologia , Íleo/cirurgia , Jejuno/cirurgia , Lactobacillus , Masculino , Proteobactérias , RNA Ribossômico 16S , Ratos , Índice de Gravidade de Doença , Síndrome do Intestino Curto/complicações , Síndrome do Intestino Curto/metabolismoRESUMO
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 (Pâ¯=â¯0.004), Klebsiella (Pâ¯=â¯0.015), Citrobacter (Pâ¯=â¯0.019), and Lactobacillus (Pâ¯=â¯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.
Assuntos
Bactérias , Microbioma Gastrointestinal/genética , Síndrome do Intestino Curto/microbiologia , Bactérias/classificação , Bactérias/genética , Bactérias/isolamento & purificação , Estudos de Casos e Controles , Colo/microbiologia , Fezes/microbiologia , Humanos , Lactente , Intestino Delgado/microbiologia , Estomas CirúrgicosRESUMO
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.
Assuntos
Bactérias/classificação , Fezes/microbiologia , Sequenciamento de Nucleotídeos em Larga Escala/métodos , Intestino Delgado/microbiologia , Síndrome do Intestino Curto/microbiologia , Bactérias/genética , Estudos de Casos e Controles , Criança , Pré-Escolar , Feminino , Humanos , Masculino , Estudos Prospectivos , RNA Ribossômico 16S/genética , Análise de Sequência de DNA/métodosRESUMO
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.
Assuntos
Microbioma Gastrointestinal , Intestinos/microbiologia , Síndrome do Intestino Curto/microbiologia , Humanos , Prebióticos , Probióticos/uso terapêutico , Síndrome do Intestino Curto/terapiaRESUMO
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.
Assuntos
Acidose Láctica/terapia , Transplante de Microbiota Fecal/métodos , Microbioma Gastrointestinal , Ácido Láctico/sangue , Síndrome do Intestino Curto/complicações , Acidose Láctica/sangue , Acidose Láctica/microbiologia , Criança , Feminino , Humanos , Síndrome do Intestino Curto/sangue , Síndrome do Intestino Curto/microbiologia , Resultado do TratamentoRESUMO
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.