Evaluating the accuracy and reproducibility of ChatGPT-4 in answering patient questions related to small intestinal bacterial overgrowth

BACKGROUND Small intestinal bacterial overgrowth(SIBO)poses diagnostic and treatment challenges due to its complex management and evolving guidelines.Patients often seek online information related to their health,prompting interest in large language models,like GPT-4,as potential sources of patient education.AIM To investigate ChatGPT-4's accuracy and reproducibility in responding to patient questions related to SIBO.METHODS A total of 27 patient questions related to SIBO were curated from professional societies,Facebook groups,and Reddit threads.Each question was entered into GPT-4 twice on separate days to examine reproducibility of accuracy on separate occasions.GPT-4 generated responses were independently evaluated for accuracy and reproducibility by two motility fellowship-trained gastroenterologists.A third senior fellowship-trained gastroenterologist resolved disagreements.Accuracy of responses were graded using the scale:(1)Comprehensive;(2)Correct but inadequate;(3)Some correct and some incorrect;or(4)Completely incorrect.Two responses were generated for every question to evaluate reproducibility in accuracy.RESULTS In evaluating GPT-4's effectiveness at answering SIBO-related questions,it provided responses with correct information to 18/27(66.7%)of questions,with 16/27(59.3%)of responses graded as comprehensive and 2/27(7.4%)responses graded as correct but inadequate.The model provided responses with incorrect information to 9/27(33.3%)of questions,with 4/27(14.8%)of responses graded as completely incorrect and 5/27(18.5%)of responses graded as mixed correct and incorrect data.Accuracy varied by question category,with questions related to“basic knowledge”achieving the highest proportion of comprehensive responses(90%)and no incorrect responses.On the other hand,the“treatment”related questions yielded the lowest proportion of comprehensive responses(33.3%)and highest percent of completely incorrect responses(33.3%).A total of 77.8%of questions yielded reproducible responses.CONCLUSION Though GPT-4 shows promise as a supplementary tool for SIBO-related patient education,the model requires further refinement and validation in subsequent iterations prior to its integration into patient care.

Progress in Diagnosis and Treatment of Small Intestinal Bacterial Overgrowth

Small intestinal bacterial overgrowth has been found to be associated with a variety of gastrointestinal disorders such as irritable bowel syndrome, inflammatory bowel disease, and, in recent years, diabetes mellitus and systemic sclerosis, among other extraintestinal diseases. Several novel diagnostic tools for small intestinal bacterial overgrowth have emerged in recent years, and several therapeutic approaches have been proposed. Therefore, it has become necessary to find an effective, safe, and simple diagnostic method and a safe treatment modality. This article provides a review of current diagnostic and therapeutic approaches to small intestinal bacterial overgrowth.

Small intestinal bacterial overgrowth syndrome

Human intestinal microbiota create a complex polymi-crobial ecology. This is characterised by its high population density, wide diversity and complexity of interaction. Any dysbalance of this complex intestinal microbiome, both qualitative and quantitative, might have serious health consequence for a macro-organism, including small intestinal bacterial overgrowth syndrome (SIBO).SIBO is defined as an increase in the number and/or alteration in the type of bacteria in the upper gastro-intestinal tract. There are several endogenous defence mechanisms for preventing bacterial overgrowth: gastric acid secretion, intestinal motility, intact ileo-caecal valve, immunoglobulins within intestinal secretion and bacte-riostatic properties of pancreatic and biliary secretion. Aetiology of SIBO is usually complex, associated with disorders of protective antibacterial mechanisms (e.g. achlorhydria, pancreatic exocrine insuff iciency, immuno-deficiency syndromes), anatomical abnormalities (e.g. small intestinal obstruction, diverticula, f istulae, surgical blind loop, previous ileo-caecal resections) and/or motility disorders (e.g. scleroderma, autonomic neuropathy in diabetes mellitus, post-radiation enteropathy, small intestinal pseudo-obstruction). In some patients more than one factor may be involved. Symptoms related to SIBO are bloating, diarrhoea, malabsorption, weight loss and malnutrition. The gold standard for diagnosing SIBO is still microbial investigation of jejunal aspirates. Noninvasive hydrogen and methane breath tests are most commonly used for the diagnosis of SIBO using glucose or lactulose. Therapy for SIBO must be com-plex, addressing all causes, symptoms and complica-tions, and fully individualised. It should include treatment of the underlying disease, nutritional support and cyclical gastro-intestinal selective antibiotics. Prognosis is usually serious, determined mostly by the underlying disease that led to SIBO.

Intestinal bacterial overgrowth in the early stage of severe acute pancreatitis is associated with acute respiratory distress syndrome

BACKGROUND In the early stage of acute pancreatitis(AP),a large number of cytokines induced by local pancreatic inflammation seriously damage the intestinal barrier function,and intestinal bacteria and endotoxins enter the blood,causing inflammatory storm,resulting in multiple organ failure,infectious complications,and other disorders,eventually leading to death.Intestinal failure occurs early in the course of AP,accelerating its development.As an alternative method to detect small intestinal bacterial overgrowth,the hydrogen breath test is safe,noninvasive,and convenient,reflecting the number of intestinal bacteria in AP indirectly.This study aimed to investigate the changes in intestinal bacteria measured using the hydrogen breath test in the early stage of AP to clarify the relationship between intestinal bacteria and acute lung injury(ALI)/acute respiratory distress syndrome(ARDS).Early clinical intervention and maintenance of intestinal barrier function would be highly beneficial in controlling the development of severe acute pancreatitis(SAP).AIM To analyze the relationship between intestinal bacteria change and ALI/ARDS in the early stage of SAP.METHODS A total of 149 patients with AP admitted to the intensive care unit of the Digestive Department,Xuanwu Hospital,Capital Medical University from 2016 to 2019 were finally enrolled,following compliance with the inclusion and exclusion criteria.The results of the hydrogen breath test within 1 wk of admission were collected,and the hydrogen production rates at admission,72 h,and 96 h were calculated.The higher the hydrogen production rates the more bacteria in the small intestine.First,according to the improved Marshall scoring system in the 2012 Atlanta Consensus on New Standards for Classification of Acute Pancreatitis,66 patients with a PaO2/FiO2 score≤1 were included in the mild AP(MAP)group,18 patients with a PaO2/FiO2 score≥2 and duration<48 h were included in the moderately SAP(MSAP)group,and 65 patients with a PaO2/FiO2 score≥2 and duration>48 h were included in the SAP group,to analyze the correlation between intestinal bacterial overgrowth and organ failure in AP.Second,ALI(PaO2/FiO2=2)and ARDS(PaO2/FiO2>2)were defined according to the simplified diagnostic criteria proposed by the 1994 European Union Conference.The MSAP group was divided into two groups according to the PaO2/FiO2 score:15 patients with PaO2/FiO2 score=2 were included in group A,and three patients with score>2 were included in group B.Similarly,the SAP group was divided into two groups:28 patients with score=2 were included in group C,and 37 patients with score>2 were included in group D,to analyze the correlation between intestinal bacterial overgrowth and ALI/ARDS in AP.RESULTS A total of 149 patients were included:66 patients in the MAP group,of whom 53 patients were male(80.3%)and 13 patients were female(19.7%);18 patients in the MSAP group,of whom 13 patients were male(72.2%)and 5 patients were female(27.8%);65 patients in the SAP group,of whom 48 patients were male(73.8%)and 17 patients were female(26.2%).There was no significant difference in interleukin-6 and procalcitonin among the MAP,MSAP,and SAP groups(P=0.445 and P=0.399,respectively).There was no significant difference in the growth of intestinal bacteria among the MAP,MSAP,and SAP groups(P=0.649).There was no significant difference in the growth of small intestinal bacteria between group A and group B(P=0.353).There was a significant difference in the growth of small intestinal bacteria between group C and group D(P=0.038).CONCLUSION Intestinal bacterial overgrowth in the early stage of SAP is correlated with ARDS.

Levothyroxine therapy and impaired clearance are the strongest contributors to small intestinal bacterial overgrowth: Results of a retrospective cohort study

AIM To identify a set of contributors, and weight and rank them on a pathophysiological basis.METHODS Patients who have undergone a lactulose or glucose hydrogen breath test to rule out small intestinal bacterial overgrowth(SIBO) for various clinical symptoms, including diarrhoea, weight loss, abdominal pain, cramping or bloating, were seen as eligible for inclusion in a retrospective single-centre study. Clinical data such as co-morbidities, medication, laboratory parameters and other possible risk factors have been identified from the electronic data system. Cases lacking or with substantially incomplete clinical data were excluded from the analysis. Suspected contributors were summarised under four different pathophysiological pathways(impaired gastric acid barrier, impaired intestinal clearance, immunosuppression and miscellaneous factors including thyroid gland variables) and investigated using the χ2 test, Student's t-test and logistic regression models.RESULTS A total of 1809 patients who had undergone hydrogen breath testing were analysed. Impairment of the gastric acid barrier(gastrectomy, odds ratio: OR = 3.5, PPI therapy OR = 1.4), impairment of intestinal clearance(any resecting gastric surgery OR = 2.6, any colonicresection OR = 1.9, stenosis OR = 3.4, gastroparesis OR = 3.4, neuropathy 2.2), immunological factors(any drug-induced immunosuppression OR = 1.8), altered thyroid gland metabolism(hypothyroidism OR = 2.6, levothyroxine therapy OR = 3.0) and diabetes mellitus(OR = 1.9) were associated significantly to SIBO. Any abdominal surgery, ileocecal resection, vagotomy or Ig A-deficiency did not have any influence, and a history of appendectomy decreased the risk of SIBO. Multivariate analysis revealed gastric surgery, stenoses, medical immunosuppression and levothyroxine to be the strongest predictors. Levothyroxine therapy was the strongest contributor in a simplified model(OR = 3.0).CONCLUSION The most important contributors for the development of SIBO in ascending order are immunosuppression, impairment of intestinal clearance and levothyroxine use, but they do not sufficiently explain its emergence.

Gut dysbiosis and small intestinal bacterial overgrowth as independent forms of gut microbiota disorders in cirrhosis

BACKGROUND Gut dysbiosis and small intestinal bacterial overgrowth(SIBO)are commonly observed in patients with cirrhosis.Despite the substantial number of articles describing the relations between disorders of gut microbiota and various manifestations of cirrhosis,dysbiosis and SIBO were always studied separately.AIM To study the relationship of gut dysbiosis and SIBO in cirrhosis.METHODS This observational study included 47 in-patients with cirrhosis.Stool microbiome was assessed using 16 S r RNA gene sequencing.SIBO was assessed using the lactulose hydrogen breath test.RESULTS SIBO was found in 24/47(51.1%)patients.Patients with SIBO had a higher abundance of Firmicutes(P=0.017)and Fusobacteria(P=0.011),and a lower abundance of Bacteroidetes(P=0.013)than patients without SIBO.This increase in the abundance of Firmicutes occurred mainly due to an increase in the abundance of bacteria from the genus Blautia(P=0.020)of the Lachnospiraceae family(P=0.047),while the abundance of other major families of this phylum[Ruminococcaceae(P=0.856),Peptostreptococcaceae(P=0.066),Clostridiaceae(P=0.463),Eubacteriaceae(P=0.463),Lactobacillaceae(P=0.413),and Veillonellaceae(P=0.632)]did not differ significantly between the patients with and without SIBO.Reduced level of Bacteroidetes in samples from patients with SIBO was a result of the decrease in bacterial numbers from all the major families of this phylum[Bacteroidaceae(P=0.014),Porphyromonadaceae(P=0.002),and Rikenellaceae(P=0.047)],with the exception of Prevotellaceae(P=0.941).There were no significant differences in the abundance of taxa that were the main biomarkers of cirrhosis-associated gut dysbiosis[Proteobacteria(P=0.790),Bacilli(P=0.573),Enterobacteriaceae(P=0.632),Streptococcaceae(P=0.170),Staphylococcaceae(P=0.450),and Enterococcaceae(P=0.873)]between patients with and without SIBO.CONCLUSION Despite the differences observed in the gut microbiome between patients with and without SIBO,gut dysbiosis and SIBO are most likely independent disorders of gut microbiota in cirrhosis.

ICC density predicts bacterial overgrowth in a rat model of post-infectious IBS

AIM:To investigate the interstitial cells of Cajal(ICC) number using a new rat model.METHODS:Sprague-Dawley rats were assigned to two groups.The first group received gavage with Campylobacter jejuni(C.jejuni) 81-176.The second group was gavaged with placebo.Three months after clearance of Campylobacter from the stool,precise segments of duodenum,jejunum,and ileum were ligated in self-contained loops of bowel that were preserved in anaerobic bags.Deep muscular plexus ICC(DMP-ICC) were quantified by two blinded readers assessing the tissue in a random,coded order.The number of ICC per villus was compared among controls,Campylobacter recovered rats without small intestinal bacterial overgrowth(SIBO),and Campylobacter recovered rats with SIBO.RESULTS:Three months after recovery,27% of rats gavaged with C.jejuni had SIBO.The rats with SIBO had a lower number of DMP-ICC than controls in the jejunum and ileum.Additionally there appeared to be a density threshold of 0.12 DMP-ICC/villus that was associated with SIBO.If ileal density of DMP-ICC was < 0.12 ICC/villus,54% of rats had SIBO compared to 9% among ileal sections with > 0.12(P<0.05).If the density of ICC was < 0.12 DMP-ICC/villus in more than one location of the bowel,88% of these had SIBO compared to 6% in those who did not(P<0.001).CONCLUSION:In this post-infectious rat model,the development of SIBO appears to be associated with a reduction in DMP-ICC.Further study of this rat model might help understand the pathophysiology of postinfectious irritable bowel syndrome.

Helicobacter pylori infection and small intestinal bacterial overgrowth–more than what meets the eye

Helicobacter pylori(H.pylori)infection is very common and affects a significant proportion of the world population.In contrast,the prevalence of small intestinal bacterial overgrowth(SIBO)in the general population is not well understood.There can be coexistence of both disease states in a given patient and their clinical symptoms may also overlap with one and another.There is no clear clinical guidelines for testing for and treating SIBO in patients with H.pylori infection.This review article explores the available evidence on the relationship between H.pylori infection and SIBO,diagnosis and treatment of these entities and also comments on associated non-gastrointestinal conditions.

Diet and intestinal bacterial overgrowth: Is there evidence?

The intestinal microbiota and its role in health and disease processes have been the subject of several studies.It is known that changes in the intestinal microbiota occur due to several factors,such as the use of medication,age,lifestyle and diseases,which can modify intestinal homeostasis and lead to excessive growth of bacteria in the small intestine,triggering a clinical condition called small bowel bacterial overgrowth(SIBO).Individuals with SIBO may present gastrointestinal symptoms ranging from nausea,diarrhea and/or constipation,and flatulence to distension and abdominal pain,resulting from poor absorption of nutrients or changes in intestinal permeability.The gold-standard treatment is based on the use of antibiotics to eradicate bacterial overgrowth.Some studies have evaluated diets in the treatment of SIBO;however,the studies are of low methodological quality,making extrapolation of the results to clinical practice unfeasible.Thus,there is still not enough scientific evidence to support a specific type of diet for the treatment of SIBO.

Probiotics and gut health:A special focus on liver diseases

Probiotic bacteria have well-established beneficial ef-fects in the management of diarrhoeal diseases.Newer evidence suggests that probiotics have the potential to reduce the risk of developing inflammatory bowel diseases and intestinal bacterial overgrowth after gut surgery.In liver health,the main benefits of probiotics might occur through preventing the production and/or uptake of lipopolysaccharides in the gut,and therefore reducing levels of low-grade inflammation.Specific immune stimulation by probiotics through processes involving dendritic cells might also be beneficial to the host immunological status and help prevent pathogen translocation.Hepatic fat metabolism also seems to be influenced by the presence of commensal bacteria,and potentially by probiotics;although the mechanisms by which probiotic might act on the liver are still unclear.However,this might be of major importance in the fu-ture because low-grade inflammation,hepatic fat infil-tration,and hepatitis might become more prevalent as a result of high fat intake and the increased prevalence of obesity.

Progress in elucidating the relationship between Helicobacter pylori infection and intestinal diseases

Helicobacter pylori(H.pylori)infection causes changes to the intestinal flora,such as small intestinal bacterial overgrowth,and increases gastric acid secretionstimulating gastrointestinal hormones,mainly gastrin,due to a decrease in gastric acid caused by atrophic gastritis.In addition,the cellular components of H.pylori travel through the intestinal tract,so the bacterial infection affects the immune system.Therefore,the effects of H.pylori infection are observed not only in the stomach and the proximal duodenum but also in the small and large intestines.In particular,meta-analyses reported that H.pylori-infected individuals had an increased risk of colorectal adenoma and colorectal cancer.Moreover,a recent study reported that the risk of developing colorectal cancer was increased in subjects carrying H.pylori vacuolating cytotoxin A antibody.In addition,it has been reported that H.pylori infection exacerbates the symptoms of Fabry’s disease and familial Mediterranean fever attack and is involved in irritable bowel syndrome and small intestinal ulcers.On the other hand,some studies have reported that the frequency of ulcerative colitis,Crohn’s disease,and celiac disease is low in H.pylori-infected individuals.Thus,H.pylori infection is considered to have various effects on the small and large intestines.However,few studies have reported on these issues,and the details of their effects have not been well elucidated.Therefore,additional studies are needed.

Washed microbiota transplantation reduces proton pump inhibitor dependency in nonerosive reflux disease

BACKGROUND The pathogenesis of gastroesophageal reflux disease(GERD)is closely associated with the intestinal bacteria composition and their metabolites.AIM To investigate whether washed microbiota transplantation(WMT)improves symptoms of nonerosive reflux disease(NERD)with proton pump inhibitor(PPI)dependency.METHODS Patients with recurrent NERD and PPI dependency at the First Affiliated Hospital of Guangdong Pharmaceutical University from 2017 to 2018 were included and divided into a WMT or PPI group treated with PPI with/without WMT.The endpoint was NERD symptom frequency evaluated 1 mo after WMT using reflux disease questionnaire(RDQ)and GERD questionnaire(GERDQ)scores,remission time,PPI dose,and the examination of intestinal mucosal barrier function.RESULTS In the WMT(n=15)and PPI(n=12)groups,the total remission rate at 1 mo after treatment was 93.3%vs 41.7%.Compared with the PPI group,the WMT group showed better results in GERDQ(P=0.004)and RDQ(P=0.003)and in remission months(8 vs 2,P=0.002).The PPI dose was reduced to some extent for 80%of patients in the WMT group and 33.3%in the PPI group.In 24 patients,intestinal mucosal barrier function was examined before treatment,and changes in the degree of damage were observed in 13 of these patients after treatment.Only one of the 15 patients had minor side effects,including a mushy stool two or three times a day,which resolved on their own after 1 wk.CONCLUSION This study is the first to demonstrate that WMT may be safe and effective for relieving NERD symptoms and reducing PPI dependency and recurrence.

Cisapride decreasing orocecal transit time in patients with nonalcoholic steatohepatitis

BACKGROUND : Altered small-intestine motility, lengthening of orocecal transit time (OCTT), and small-intestinal bacterial overgrowth (SIBO) have been detected in patients with nonalcoholic steatohepatitis (NASH). These changes might be related to the progressive course and poor prognosis of the disease. This study was undertaken to investigate the effect of 4-week treatment with cisapride on OCTT. METHODS: Ten NASH patients without diabetes were included. Ten healthy individuals served as controls. OCTT was measured by lactulose breath test (LBT). Anti- endotoxin core antibodies (EndoCAb) IgG were also examined. The effect of cisapride (10 mg TID during 4 weeks) on LBT and serum EndoCAb IgG levels in NASH patients was investigated. RESULTS: The NASH patients had more significantly prolonged OCTT (95±17 min) than the controls (59±18 min, P=0.00032). Cisapride administration decreased OCTT (from 95±17 min to 83±19 min, P=0.037), basal breathed H2 (from 9.87±1.60 ppm to 8.61±1.63 ppm, P=0.046) and EndoCAb IgG titers (from 5.24±0.68 GMU/ ml to 4.20±0.72 GMU/ml, P=0.013) in NASH patients. CONCLUSIONS: The present data suggest the existence of deranged intestinal motility and endotoxemia in NASH patients. Cisapride administration during 4 weeks possibly restore intestinal motility and ameliorate endotoxemia in NASH patients.

Quantitative analysis of intestinal gas in patients with acute pancreatitis

BACKGROUND: Disturbance of gastrointestinal function is a common complication in the early phase of acute pancreatitis (AP). Intestinal gas may reflect the function of the gut. Using plain abdominal radiographs, we investigated whether intestinal gas volume is related to AP. METHODS: Plain abdominal radiographs of 68 patients with AP within 24 hours after admission and 21 normal controls were digitized and transmitted to a computer. The region of intestinal gas was identified by an image manipulation software and the gas volume score (GVS) was calculated. The relationships between the GVS values and various clinical factors of AP were analyzed. RESULTS: The GVS in the AP group was 0.084±0.016, in the mild AP (MAP) group 0.070±0.005, and in the severe AP (SAP) group 0.094±0.013; all values were higher than that in the control group (P<0.01). The GVS in the SAP group was higher than that in the MAP group. The GVSs were correlated to the Ranson’s scores (r=0.762, P<0.01) and the acute physiology and chronic health evaluation II (APACHE II) scores (r=0.801, P<0.01). In addition, the GVS in patients with secondary pancreatic and/or peripancreatic infection was 0.107±0.014, higher than that in patients without secondary infection (P<0.01). GVS was not related to gender, age, etiology or clinical outcome of AP. CONCLUSIONS: Intestinal gas volume is significantly elevated in patients with AP. It is closely related to Ranson’s and APACHE II score and secondary pancreatic and/or peripancreatic infection. GVS may be a new prognostic tool for assessing the severity of AP in the early course of the disease.

Gut-liver axis in cirrhosis:Are hemodynamic changes a missing link?

Recent evidence suggests that the condition of the gut and its microbiota greatly influence the course of liver disease,especially cirrhosis.This introduces the concept of the gut-liver axis,which can be imagined as a chain connected by several links.Gut dysbiosis,small intestinal bacterial overgrowth,and intestinal barrier alteration lead to bacterial translocation,resulting in systemic inflammation.Systemic inflammation further causes vasodilation,arterial hypotension,and hyperdynamic circulation,leading to the aggravation of portal hypertension,which contributes to the development of complications of cirrhosis,resulting in a poorer prognosis.The majority of the data underlying this model were obtained initially from animal experiments,and most of these correlations were further reproduced in studies including patients with cirrhosis.However,despite the published data on the relationship of the disorders of the gut microbiota with the complications of cirrhosis and the proposed pathogenetic role of hemodynamic disorders in their development,the direct relations between gut dysbiosis and hemodynamic changes in this disease are poorly studied.They remain a missing link in the gut-liver axis and a challenge for future research.

Glucose substrate in the hydrogen breath test for gut microbiota determination:A recommended noninvasive test

Intestinal dysbiosis and small intestinal bacterial overgrowth(SIBO)are common in patients with liver cirrhosis.Existing studies have not explored the association between gut dysbiosis and SIBO.We propose some suggestions for the authors’experimental methods and concepts,and we hope these suggestions can be adopted.The hydrogen breath test is worthy of recommendation due to its high accuracy and convenient operation.We suggest changing the substrate of the hydrogen breath test from lactulose to glucose to improve the accuracy of each parameter.SIBO is a small subset of gut dysbiosis,and we propose clarifying the concept of both.SIBO may be caused by liver cirrhosis or one of the pathogeneses of gastrointestinal diseases.Therefore,interference from other gastrointestinal diseases should be excluded from this study.

Patients with breath test positive are necessary to be identified from irritable bowel syndrome:a clinical trial based on microbiomics and rifaximin sensitivity

Background:As a non-invasive and effective diagnostic method for small intestinal bacterial overgrowth(SIBO),wild-use of breath test(BT)has demonstrated a high comorbidity rate in patients with diarrhea-predominant irritable bowel syndrome(IBS-D)and SIBO.Patients overlapping with SIBO respond better to rifaximin therapy than those with IBS-D only.Gut microbiota plays a critical role in both of these two diseases.We aimed to determine the microbial difference between IBS-D overlapping with/without SIBO,and to study the underlying mechanism of its sensitivity to rifaximin.Methods:Patients with IBS-D were categorized as BT-negative(IBSN)and BT-positive(IBSP).Healthy volunteers(BT-negative)were enrolled as healthy control.The patients were clinically evaluated before and after rifaximin treatment(0.4 g bid,4 weeks).Blood,intestine,and stool samples were collected for cytokine assessment and gut microbial analyses.Results:Clinical complaints and microbial abundance were significantly higher in IBSP than in IBSN.In contrast,severe systemic inflammation and more active bacterial invasion function that were associated with enrichment of opportunistic pathogens were seen in IBSN.The symptoms of IBSP patients were relieved in different degrees after therapy,but the symptoms of IBSN rarely changed.We also found that the presence of IBSN-enriched genera(Enterobacter and Enterococcus)are unaffected by rifaximin therapy.Conclusions:IBS-D patients overlapping with SIBO showed noticeably different fecal microbial composition and function compared with IBS-D only.The better response to rifaximin in those comorbid patients might associate with their different gut microbiota,which suggests that BT is necessary before IBS-D diagnosis and use of rifaximin.Registration:Chinese Clinical Trial Registry,ChiCTR1800017911.