Clinical response to fecal microbiota transplantation in patients with diarrhea-predominant irritable bowel syndrome is associated with normalization of fecal microbiota composition and short-chain fatty acid levels

Objectives: Irritable bowel syndrome (IBS) may be associated with disturbances in gut microbiota composition and functions. We recently performed a study of fecal microbiota transplantation (FMT) in diarrhea-predominant IBS (IBS-D) and found that IBS symptoms improved and the gut microbiota profile changed following FMT. We now aimed to explore the effects of FMT on the gut microenvironment in further detail by using 16S rRNA sequencing for more extended microbiota profiling and analyzing bacterial fermentation products (SCFAs: short chain fatty acids).

Materials and methods: The study included 13 patients (four females and nine males) with IBS-D according to Rome III criteria and 13 healthy donors. Freshly donated feces were administered into duodenum via gastroscopy. The patients completed symptom and quality of life (QoL) questionnaires and delivered feces before and 1, 3, 12 and 20/28 weeks after FMT. Microbiota analysis was performed by sequencing 16S rRNA gene with Illumina Miseq technology. Fecal concentrations of SCFAs were analyzed by vacuum distillation followed by gas chromatography.

Results: Several gut microbiota taxa and SCFAs were significantly different in the patients at baseline compared to their donors. These differences normalized by the third week following FMT in parallel with significant improvement in symptoms and QoL. Responders had different gut microbiota profile and SCFAs than nonresponders. Significant correlations were found between the gut microenvironment and IBS symptoms. No adverse effects were reported.

Conclusions: FMT restores alterations of the gut microenvironment in IBS-D patients during the first 3 weeks and improves their symptoms for up to 28 weeks.

ClinicalTrials.gov ID: NCT03333291.     

High-throughput DNA sequence analysis reveals stable engraftment of gut microbiota following transplantation of previously frozen fecal bacteria

Fecal microbiota transplantation (FMT) is becoming a more widely used technology for treatment of recurrent Clostridum difficile infection (CDI). While previous treatments used fresh fecal slurries as a source of microbiota for FMT, we recently reported the successful use of standardized, partially purified and frozen fecal microbiota to treat CDI. Here we report that high-throughput 16S rRNA gene sequencing showed stable engraftment of gut microbiota following FMT using frozen fecal bacteria from a healthy donor. Similar bacterial taxa were found in post-transplantation samples obtained from the recipients and donor samples, but the relative abundance varied considerably between patients and time points. Post FMT samples from patients showed an increase in the abundance of Firmicutes and Bacteroidetes, representing 75–80% of the total sequence reads. Proteobacteria and Actinobacteria were less abundant (< 5%) than that found in patients prior to FMT. Post FMT samples from two patients were very similar to donor samples, with the Bacteroidetes phylum represented by a great abundance of members of the families Bacteroidaceae, Rikenellaceae and Porphyromonadaceae, and were largely comprised of Bacteroides, Alistipes and Parabacteroides genera. Members of the phylum Firmicutes were represented by Ruminococcaceae, Lachnospiraceae, Verrucomicrobiaceae and unclassified Clostridiales and members of the Firmicutes. One patient subsequently received antibiotics for an unrelated infection, resulting in an increase in the number of intestinal Proteobacteria, primarily Enterobacteriaceae. Our results demonstrate that frozen fecal microbiota from a healthy donor can be used to effectively treat recurrent CDI resulting in restoration of the structure of gut microbiota and clearing of Clostridum difficile.     

Clinical results and microbiota changes after faecal microbiota transplantation for chronic pouchitis: a pilot study

Abstract

Objectives: Research evidence suggests that chronic pouchitis is associated with intestinal dysbiosis. Faecal microbiota transplantation (FMT) has been proposed as a possible treatment. We performed a 6-month prospective, open-label, single-centre cohort pilot-study (NCT03538366) to investigate if FMT could improve clinical outcome and alter gut microbiota in patients with chronic pouchitis.

Materials and methods: Nine adult patients with chronic pouchitis were included and allocated to 14?days FMT by enemas from five faecal donors, with a 6-month follow-up. Pouchitis severity was assessed using pouchitis disease activity index (PDAI) before and after FMT. Changes in gut microbiota, and engraftment of donor’s microbiota were assessed in faecal samples.

Results: All patients were treated with FMT for 14 continuous days. Overall, four of nine patients receiving FMT were in clinical remission at 30-day follow-up, and three patients remained in remission until 6-month follow-up. Clinical symptoms of pouchitis improved significantly between inclusion and 14-day follow-up (p?=?.02), but there was no improvement in PDAI between inclusion (mean 8.6) and 30-day follow-up (mean 5.2). Treatment with FMT caused a substantial shift in microbiota and increased microbial diversity in six patients, resembling that of the donors, with a high engraftment of specific donor microbiota.

Conclusions: Symptomatic benefit in FMT treatment was found for four of nine patients with chronic pouchitis with increased microbial diversity and high engraftment of donor’s microbiota. A larger, randomised controlled study is required to fully evaluate the potential role of FMT in treating chronic pouchitis.     

Limited engraftment of donor microbiome via one-time fecal microbial transplantation in treated HIV-infected individuals

Many HIV-infected individuals on antiretroviral therapy (ART) exhibit persistent systemic inflammation, which predicts morbidity and mortality. ART-treated subjects concurrently exhibit marked compositional alterations in the gut bacterial microbiota and the degree of dysbiosis correlates with systemic inflammation. Whether interventions to modulate the microbiome can affect systemic inflammation is unknown. An open-label fecal microbial transplantation (FMT) was delivered by colonoscopy to asymptomatic HIV-infected ART-suppressed individuals without antibiotic pre-treatment. Stool was assessed before and after FMT for engraftment of donor microbes, and peripheral blood was assayed for immune activation biomarkers. Six participants received FMT and 2 participants served as controls. No serious adverse effects occurred during 24 weeks of follow-up. At baseline, HIV-infected individuals exhibited microbiota profiles distinct from uninfected donors. During the 8 weeks post-FMT, recipients demonstrated partial engraftment of the donor microbiome (P < 0.05). Recipient microbiota remained significantly distant from donors, unlike that observed following FMT for treatment of C. difficile infection. Systemic inflammatory markers showed no significant change post-FMT. FMT was well-tolerated in ART-treated, HIV-infected individuals. Engraftment was detectable but modest, and appeared to be limited to specific bacterial taxa. Whether antibiotic conditioning can enhance engraftment and the capacity of microbiota to modulate inflammation remains to be investigated.     

粪菌移植对肠易激综合征临床疗效和肠道菌群影响的非对照初步研究

目的:探讨粪菌移植治疗IBS的有效性、安全性及其对IBS患者肠道菌群的影响。方法:选择2016年9月至2017年8月在广州市第一人民医院行粪菌移植的IBS住院患者28例。所有IBS患者于粪菌移植前、粪菌移植后4和12周完成肠易激综合征生活质量量表(IBS-QOL)、肠易激综合征严重程度系统评分(IBS-SSS)和胃肠道...     

Microbial composition analysis of Clostridium difficile infections in an ulcerative colitis patient treated with multiple fecal microbiota transplantations

Fecal microbiota transplantation (FMT) is a promising therapy for Clostridium difficile infection (CDI). However, questions remain regarding efficacy and safety in inflammatory bowel disease (IBD) patients, as well as longitudinal stability of donor stool composition. This report describes an IBD patient with two CDIs 18 months apart, each successfully treated with FMT with no IBD flares or complications. Microbiome composition analysis of patient samples during each infection revealed low-diversity microbiota patterns similar to those previously described in non-IBD patients with CDI and active IBD alone. Samples taken after each transplant demonstrated quick remodeling towards the donor's sample composition coinciding with symptom resolution. Of note, samples taken from the same donor 18 months apart reflected marked differences in microbiota abundances, suggesting that the use of single donors in FMT programs offers little benefit in ensuring predictability of donor stool composition over time. This report describes similar microbial composition patterns during CDI in IBD patients to those described previously in non-IBD patients, and supports FMT as safe and effective treatment for recurring CDI in this patient population.     

Responses to faecal microbiota transplantation in female and male patients with irritable bowel syndrome

BACKGROUNDFaecal microbiota transplantation (FMT) seems to be a promising treatment for irritable bowel syndrome (IBS) patients. In Western countries (United States and Europe), there is a female predominance in IBS. A sex difference in the response to FMT has been reported recently in IBS patients.AIMTo investigate whether there was a sex difference in the response to FMT in the IBS patients who were included in our previous randomized controlled trial of the efficacy of FMT.METHODSThe study included 164 IBS patients who participated in our previous randomized controlled trial. These patients had moderate-to-severe IBS symptoms belonging to the IBS-D (diarrhoea-predominant), IBS-C (constipation-predominant) and IBS-M (mixed) subtypes, and had not responded to the National Institute for Health and Care Excellence (NICE)-modified diet. They belonged in three groups: placebo (own faeces), and active treated group (30-g or 60-g superdonor faeces). The patients completed the IBS severity scoring system (IBS-SSS), Fatigue Assessment Scale (FAS) and the IBS quality of life scale (IBS-QoL) questionnaires at the baseline and 2 wk, 1 mo and 3 mo after FMT. They also provided faecal samples at the baseline and 1 mo after FMT. The faecal bacteria profile and dysbiosis were determined using the 16S rRNA gene polymerase chain reaction DNA amplification covering V3-V9; probe labelling by single nucleotide extension and signal detection. The levels of short-chain fatty acids (SCFAs) were determined by gas chromatography and flame ionization.RESULTSThere was no sex difference in the response to FMT either in the placebo group or active treated group. There was no difference between females and males in either the placebo group or actively treated groups in the total score on the IBS-SSS, FAS or IBS-QoL, in dysbiosis, or in the faecal bacteria or SCFA level. However, the response rate was significantly higher in females with diarrhoea-predominant (IBS-D) than that of males at 1 mo, and 3 mo after FMT. Moreover, IBS-SSS total score was significantly lower in female patients with IBS-D than that of male patients both 1 mo and 3 mo after FMT.CONCLUSIONThere was no sex difference in the response to FMT among IBS patients with moderate-to-severe symptoms who had previously not responded to NICE-modified diet. However, female patients with IBS-D respond better and have higher reduction of symptoms than males after FMT.     

Changes in gut microbial metagenomic pathways associated with clinical outcomes after the elimination of malabsorbed sugars in an IBS cohort

ABSTRACT

Specific diets to manage sugar malabsorption are reported to reduce clinical symptoms of irritable bowel syndrome (IBS). However, the effects of diets for malabsorbed sugars on gut microbiota signatures have not been studied, and associations with clinical outcomes in IBS have not been characterized. 22 IBS patients positively tested for either lactose-, fructose-, sorbitol- or combined malabsorptions were subjected to 2-weeks sugar elimination and subsequent 4-weeks re-introduction. 7 IBS patients tested negative for sugar malabsorption were used as controls. Nutrition and clinical symptoms were recorded throughout the study. Fecal samples were serially collected for 16S rRNA amplicon and shotgun-metagenome sequencing.

Dietary intervention supervised by nutrition counseling reduced IBS symptoms during the elimination and tolerance phases. Varying clinical response rates were observed between subjects, and used to dichotomize our cohort into visual analogue scale (VAS) responders and non-responders. Alpha -and beta-diversity analyzes revealed only minor differences regarding 16S rRNA-based fecal microbiota compositions between responder and non-responder patients during baseline or tolerance phase. In shotgun-metagenome analyzes, however, we analyzed microbial metabolic pathways and found significant differences in pathways encoding starch degradation and complex amino acid biosynthesis at baseline between IBS controls and malabsorbers, and notably, between diet responder and non-responders. Faecalibacterium prausnitzii, Ruminococcus spp. and Bifidobacterium longum largely informed these metabolic pathways.

Our study demonstrates that diet interventions for specific, malabsorbed carbohydrates reshaped the metagenomic composition of the gut microbiota, with a small community of bacterial taxa contributing to these changes rather than a single species.     

Effective fecal microbiota transplantation for recurrent Clostridioides difficile infection in humans is associated with increased signalling in the bile acid-farnesoid X receptor-fibroblast growth factor pathway

The mechanisms of efficacy for fecal microbiota transplantation (FMT) in treating recurrent Clostridioides difficile infection (rCDI) remain poorly defined, with restored gut microbiota-bile acid interactions representing one possible explanation. Furthermore, the potential implications for host physiology of these FMT-related changes in gut bile acid metabolism are also not well explored. In this study, we investigated the impact of FMT for rCDI upon signalling through the farnesoid X receptor (FXR)-fibroblast growth factor (FGF) pathway. Herein, we identify that in addition to restoration of gut microbiota and bile acid profiles, FMT for rCDI is accompanied by a significant, sustained increase in circulating levels of FGF19 and reduction in FGF21. These FGF changes were associated with weight gain post-FMT, to a level not exceeding the pre-rCDI baseline. Collectively, these data support the hypothesis that the restoration of gut microbial communities by FMT for rCDI is associated with an upregulated FXR-FGF pathway, and highlight the potential systemic effect of FMT.     

Microbiota in health and irritable bowel syndrome: current knowledge,perspectives and therapeutic options

Abstract

The gastrointestinal tract is a natural reservoir of microbiota. The gut is germ-free at birth, but rapidly becomes host to various bacteria establishing a progressively mutual relationship. The composition of gut microbiota is individual-specific and depends on the genotype of the host and environmental factors. Novel techniques have been used to characterize gastrointestinal microbiota, including genomic approaches. The bacterial profile shows that dominant and minor phyla are present in the gastrointestinal tract. From the proximal to the distal segments of the gut the bacterial density gradually increases, reaching an estimated 10¹¹ to 10¹² bacteria per gram of colonic content. Dynamic interactions between gut and microbiota play a physiological role in metabolic, protective and structural functions, while dysbiosis contributes to several diseases. Microbiota appear to play a role in IBS, where qualitative and quantitative changes of bacteriaoccur in IBS subtypes. Initial therapeutic approaches in IBS have focused on microbiota. The relationship between perturbations of the microbiota, mucosal inflammation and IBS remains to be further investigated.     

Fecal microbiota transplantation for management of Clostridium difficile infection

The widespread use of antibiotics has led Clostridium difficile infection (CDI) to become a common problem with pronounced medical and economic effects. The recurrence of CDI after treatment with standard antibiotics is becoming more common with the emergence of more resistant strains of C. difficile. As CDI is an antibiotic-associated disease, further treatment with antibiotic is best avoided. As the gut flora is severely disturbed in CDI, approaches that restore the gut microbiota may become good alternative modes of CDI therapies. Fecal microbiota transplantation (FMT) is the procedure of transplantation of fecal bacteria from a healthy donor individual into a patient for restoration of the normal colonic flora. Thus, FMT helps in the eradication of C. difficile and resolution of clinical symptoms such as diarrhea, cramping, and urgency. Though this approach to treatment is not new, presently, it has become an alternative and promising way of combating infections. The procedure is not in regular use because of the time required to identify a suitable donor, the risk of introducing opportunistic pathogens, and a general patient aversion to the transplant. However, FMT is gaining popularity because of its success rate as a panacea for recurrent attacks of CDI and is being increasingly used in clinical practice. This review describes the rationale, the indications, the results, the techniques, the potential donors, the benefits as well as the complications of fecal microbiota instillation to CDI patients in order to restore the normal gut flora.     

Beneficial effects of LRP6-CRISPR on prevention of alcohol-related liver injury surpassed fecal microbiota transplant in a rat model

ABSTRACT

Alcohol intake can modify gut microbiota composition, increase gut permeability, and promote liver fibrogenesis. LRP6 is a signal transmembrane protein and a co-receptor for the canonical Wnt signaling pathway. This study compared the curative effect of LRP6-CRISPR on alcohol-related liver injury with that of traditional fecal microbiota transplant (FMT) and investigated the alteration of the gut microbiome following the treatment. A rat model of alcohol-related liver injury was established and injected with lentiviral vectors expressing LRP6-CRISPR or administered with fecal filtrate from healthy rats, with healthy rat served as the control. Liver tissues of rats were examined by HE staining, Sirius staining, and Oil red O staining, respectively. The expression of LRP6 and fibrosis biomarkers were tested by PCR. The fecal sample of rats was collected and examined by 16S rRNA sequencing. Our data indicated that LRP6-CRISPR was more efficient in the prevention of alcohol-related liver injury than FMT. Microbiome analysis showed that alcohol-related liver injury related to gut microbiota dysbiosis, while treatment with LRP6-CRISPR or FMT increased gut microflora diversity and improved gut symbiosis. Further, bacteria specific to the disease stages were identified. Genera Romboutsia, Escherichia-Shigella, Pseudomonas, Turicibacter, and Helicobacter were prevalent in the intestine of rats with alcohol-related liver injury, while the domination of Lactobacillus was found in rats treated with LRP6-CRISPR or FMT. Besides, Lactobacillus and genera belonging to family Lachnospiraceae, Bacteroidales S24-7 group, and Ruminococcaceae were enriched in healthy rats. LRP6-CRISPR and FMT have beneficial effects on the prevention of alcohol-related liver injury, and correspondently, both treatments altered the disrupted gut microflora to a healthy one.     

Selección del donante para la transferencia de microbiota fecal. Documento de posicionamiento de la Societat Catalana de Digestologia y de la Societat Catalana de Malalties Infeccioses i Microbiologia Clínica

Faecal microbiota transplantation (FMT) is an effective and safe treatment of recurrent Clostridioides difficile infection. It is essential to make every effort to perform FMT rigorously and based on scientific knowledge. Selection of the faecal microbiota donor is a key part of the process to ensure recipient safety. Protocols of action must be implemented that allow clinicians to act with the maximum guarantees and to minimise the risks of the procedure. In this regard, a multidisciplinary working group has been set up with the aim of establishing recommendations for selecting the faecal microbiota donor.     

Recomendaciones para la selección del donante para la transferencia de microbiota fecal. Documento de posicionamiento avalado por la Societat Catalana de Digestologia,la Societat Catalana de Malalties Infeccioses i Microbiologia Clínica y el grupo GEMBIOTA de la Sociedad Española de Enfermedades Infecciosas y Microbiología Clínica

Fecal microbiota transplantation (FMT) is an effective and safe treatment to treat recurrent Clostridioides difficile infection. It is essential to make every effort to perform FMT rigorously and based on scientific knowledge. Selection of the fecal microbiota donor is a key point of the process to ensure recipient safety. It is necessary to have protocols of action that allow clinicians to act with the maximum guarantees and to minimize the risks of the procedure. For this reason, a multidisciplinary working group has been set up in Cataluña with the aim of establishing recommendations for the selection of the fecal microbiota donor.     

Fecal microbiota transplantation for irritable bowel syndrome: An intervention for the 21st century

Irritable bowel syndrome (IBS) affects about 12% of the global population. Although IBS does not develop into a serious disease or increase mortality, it results in a considerable reduction in the quality of life. The etiology of IBS is not known, but the intestinal microbiota appears to play a pivotal role in its pathophysiology. There is no effective treatment for IBS, and so the applied treatments clinically focus on symptom relief. Fecal microbiota transplantation (FMT), an old Chinese treatment, has been applied to IBS patients in seven randomized controlled trials (RCTs). Positive effects on IBS symptoms in various degrees were obtained in four of these RCTs, while there was no effect in the remaining three. Across the seven RCTs there were marked differences in the selection processes for the donor and treated patients, the transplant dose, the route of administration, and the methods used to measure how the patients responded to FMT. The present frontier discusses these differences and proposes: (1) criteria for selecting an effective donor (superdonor); (2) selection criteria for patients that are suitable for FMT; (3) the optimal FMT dose; and (4) the route of transplant administration. FMT appears to be safe, with only mild, self-limiting side effects of abdominal pain, cramping, tenderness, diarrhea, and constipation. Although it is early to speculate about the mechanisms underlying the effects of FMT, the available data suggest that changes in the intestinal bacteria accompanied by changes in fermentation patterns and fermentation products (specifically short-chain fatty acids) play an important role in improving the IBS symptoms seen after FMT. FMT appears to be a promising treatment for IBS, but further studies are needed before it can be applied in everyday clinical practice.     

Gut Microbiota Characteristics in Children After the Use of Proton Pump Inhibitors

Background/Aims: Prolonged acid suppression from proton pump inhibitor (PPI) has been shown to cause gut microbiota alteration, which may increase the risk of various infections in adults. We aimed to characterize gut microbiota profiles in children after a short-term use of PPI.Materials and Methods: Children aged 1-18 years who underwent PPI therapy were included during April-December 2017. We excluded children who previously used antibiotics or acid suppressants and who had a history of acute gastroenteritis or specific food avoidance one month prior to the enrolment. The stool samples before and after the PPI use were collected for gut microbiota composition. The 16S ribosomal RNA gene sequencing was performed by using Illumina MiSeq. The differences in the gut microbiota profile after the use of PPI were compared to pre-PPI period.Results: We completed stool collection in 20 children (median age of 5.8 years and 60% were female). No significant changes in the overall number of species-level taxonomy categories or predominant bacteria belonging to the phylum (Bacteroidetes) were noted. We found a trend increase in the proportion of the phylum Firmicutes among children living in the designated metropolitan/suburban area (P = .07) and among males (P = .11). In four children with infection-related adverse effects, we noted a nonsignificant increase in the proportion of the phylum Firmicutes after the PPI use (from 35% to 52%, P = .14).Conclusions: Even the total number of and predominant gut microbiota did not significantly change after a four- to eight-week course of PPI therapy; we found a trend of increase in the proportion of the phylum Firmicutes in certain groups of children.     

The interplay between the gut microbiota and NLRP3 activation affects the severity of acute pancreatitis in mice

ABSTRACT

Early dysbiosis of the gut microbiota is associated with the severity of acute pancreatitis (AP), although the underlying mechanism is unclear. Here, we investigated the role of crosstalk between NLRP3 and the gut microbiota in the development of AP utilizing gut microbiota deficient mice, as well as NLRP3 knockout (KO) mouse models. Pancreatic damage and systemic inflammation were improved in antibiotic-treated (Abx) and germ-free (GF) mice, accompanied by weakened activity of the intestinal NLRP3 inflammasome. Interestingly, fecal microbiota transplantation (FMT) reactivated the intestinal NLRP3 inflammasome and exacerbated the disease in Abx and GF mice. Although the gut barrier in GF and Abx mice was disrupted, gut microbiota deficiency ameliorated the severity of AP, probably due to the reduction in bacterial translocation from the gut to the pancreas. The composition of the gut microbiota was significantly different between NLRP3 KO mice and wild-type (WT) mice at baseline, and there were alterations in response to the induction of AP. While a dramatic shift in the gut microbiota with overgrowth of Escherichia-Shigella was observed in WT mice suffering from AP, there was no significant change in NLRP3 KO mice with or without AP, suggesting that NLRP3 deficiency counteracts AP-induced microbial disturbance. With a strengthened gut barrier and decreased systemic inflammation, NLRP3 KO mice showed less severe AP, as revealed by reduced pancreatic neutrophilic infiltration and necrosis. Taken together, these results identified the bidirectional modulation between the gut microbiota and NLRP3 in the progression of AP, which suggests the interplay of the host and microbiome during AP.     

Fecal microbiota transplantation broadening its application beyond intestinal disorders

Intestinal dysbiosis is now known to be a complication in a myriad of diseases.Fecal microbiota transplantation(FMT),as a microbiota-target therapy,is arguably very effective for curing Clostridium difficile infection and has good outcomes in other intestinal diseases.New insights have raised an interest in FMT for the management of extra-intestinal disorders associated with gut microbiota.This review shows that it is an exciting time in the burgeoning science of FMT application in previously unexpected areas,including metabolic diseases,neuropsychiatric disorders,autoimmune diseases,allergic disorders,and tumors.A randomized controlled trial was conducted on FMT in metabolic syndrome by infusing microbiota from lean donors or from self-collected feces,with the resultant findings showing that the lean donor feces group displayed increased insulin sensitivity,along with increased levels of butyrate-producing intestinal microbiota.Case reports of FMT have also shown favorable outcomes in Parkinson's disease,multiple sclerosis,myoclonus dystonia,chronic fatigue syndrome,and idiopathic thrombocytopenic purpura.FMT is a promising approach in the manipulation of the intestinal microbiota and has potential applications in a variety of extra-intestinal conditions associated with intestinal dysbiosis.     

Comparison of gut microbiota profile in celiac disease,non-celiac gluten sensitivity and irritable bowel syndrome: A systematic review

Gut microbiota is vital for human health. Shifts in the microbial diversity can affect bacterial function, and dysbiosis is associated with a variety of gastrointestinal disorders, including celiac disease (CD) and irritable bowel syndrome (IBS). The distinction between IBS and non-celiac gluten sensitivity (NCGS) is unclear, and it is conceivable that the gut microbiota profile of these patients may overlap. To our knowledge, no existing literature has evaluated the microbial characteristics in CD, IBS, and NCGS. Hence, this systematic review aims to compare the gut microbiota profile in these three diagnoses. A literature search was conducted in PubMed (Medline) until April 2019. Studies investigating bacterial diversity in the gut of patients with CD, IBS, and NCGS were eligible. Inclusion criteria were observational studies and randomized controlled trials reporting bacterial profile at baseline. Ninety-one articles were identified, of which 13 trials were eligible for inclusion. Overall, the bacterial composition of the gut microbiota of patients with CD and those with IBS shared the many similarities. The microbial richness was correspondingly reduced in these patient-groups compared with healthy controls, but this was not reported for NCGS. Our findings suggest that the bacterial profiles of patients with IBS and CD share certain disease-specific trends. Fewer similarities were observed between the bacterial profiles of patients with IBS and NCGS. Notably, the data are limited; thus, no solid conclusions can be made on the basis of these findings alone. The suggested trends can be a valuable basis for further research.