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.

Breath test for differential diagnosis between small intestinal bacterial overgrowth and irritable bowel disease:An observation on non-absorbable antibiotics

AIM： To estimate the prevalence of small intestine bacterial overgrowth （SIBO） among patients with an earlier diagnosis of irritable bowel disease （IBS） in our geographical area, and to collect information on the use of locally acting non-absorbable antibiotics in the management of SIBO. METHODS： A non-interventional study was conducted in 73 consecutive patients with a symptom-based diagnosis.. RESULTS： When the patients underwent a ＂breath test＂, 33 （45.2%） showed the presence of a SIBO. Arcer treatment with rifaximin 1200 mg/d for seven days in 32 patients, 19 （59.4%） showed a negative ＂breath test＂ one week later as well as a significant reduction of symptoms, thus confirming the relationship between SIBO and many of the symptoms claimed by patients. In the other 13 patients, ＂breath test＂ remained positive, and a further cycle of treatment with ciprofloxacin 500 mg/d was given for 7 additional days, resulting in a negative ＂breath test＂ in one patient only. CONCLUSION： （1） about half of the patients with a symptomatic diagnosis of IBS have actually SIBO, which is responsible for most of the symptoms attributed to IBS; （2） only a ＂breath test＂ with lactulose （or with glucose in subjects with an intolerance to lactose） can provide a differential diagnosis between IBS and SIBO, with almost identical symptoms; and （3） the use of non-absorbable antibiotics may be useful to reduce the degree of SIBO and related symptoms; it must be accompanied, however, by the correction of the wrong alimentary habits underlying 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.

Subclinical atherosclerosis is linked to small intestinal bacterial overgrowth via vitamin K2-dependent mechanisms

To assess the rate of matrix Gla-protein carboxylation in patients with small intestinal bacterial overgrowth (SIBO) and to decipher its association with subclinical atherosclerosis.METHODSPatients with suspected SIBO who presented with a low risk for cardiovascular disease and showed no evidence of atherosclerotic plaques were included in the study. A glucose breath test was performed in order to confirm the diagnosis of SIBO and vascular assessment was carried out by ultrasound examination. Plasma levels of the inactive form of MGP (dephosphorylated-uncarboxylated matrix Gla-protein) were quantified by ELISA and vitamin K2 intake was estimated using a food frequency questionnaire.RESULTSThirty-nine patients were included in the study. SIBO was confirmed in 12/39 (30.8%) patients who also presented with a higher concentration of dephosphorylated-uncarboxylated matrix Gla-protein (9.5 μg/L vs 4.2 μg/L; P = 0.004). Arterial stiffness was elevated in the SIBO group (pulse-wave velocity 10.25 m/s vs 7.68 m/s; P = 0.002) and this phenomenon was observed to correlate linearly with the levels of dephosphorylated-uncarboxylated matrix Gla-protein (β = 0.220, R2 = 0.366, P = 0.03). Carotid intima-media thickness and arterial calcifications were not observed to be significantly elevated as compared to controls.CONCLUSIONSIBO is associated with reduced matrix Gla-protein activation as well as arterial stiffening. Both these observations are regarded as important indicators of subclinical atherosclerosis. Hence, screening for SIBO, intestinal decontamination and supplementation with vitamin K2 has the potential to be incorporated into clinical practice as additional preventive measures.

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.

Small intestinal bacterial overgrowth in inactive Crohn's disease:Influence of thiopurine and biological treatment

AIM: To investigate the influence of thiopurines and biological drugs on the presence of small intestinal bacterial overgrowth (SIBO) in patients with inactive Crohn&#x02019;s disease (CD).

Methane production and small intestinal bacterial overgrowth in children living in a slum

AIM:To analyze small intestinal bacterial overgrowth in school-aged children and the relationship between hydrogen and methane production in breath tests.METHODS:This transversal study included 85 children residing in a slum and 43 children from a private school,all aged between 6 and 10 years,in Osasco,Brazil.For characterization of the groups,data regarding the socioeconomic status and basic housing sanitary conditions were collected.Anthropometric data was obtained in children from both groups.All children completed the hydrogen(H 2) and methane(CH 4) breath test in order to assess small intestinal bacterial overgrowth(SIBO).SIBO was diagnosed when there was an increase in H 2 ≥ 20 ppm or CH 4 ≥ 10 ppm with regard to the fasting value until 60 min after lactulose ingestion.RESULTS:Children from the slum group had worse living conditions and lower nutritional indices than children from the private school.SIBO was found in 30.9%(26/84) of the children from the slum group and in 2.4%(1/41) from the private school group(P = 0.0007).Greater hydrogen production in the small intestine was observed in children from the slum group when compared to children from the private school(P = 0.007).A higher concentration of hydrogen in the small intestine(P < 0.001) and in the colon(P < 0.001) was observed among the children from the slum group with SIBO when compared to children from the slum group without SIBO.Methane production was observed in 63.1%(53/84) of the children from the slum group and in 19.5%(8/41) of the children from the private school group(P < 0.0001).Methane production was observed in 38/58(65.5%) of the children without SIBO and in 15/26(57.7%) of the children with SIBO from the slum.Colonic production of hydrogen was lower in methaneproducing children(P = 0.017).CONCLUSION:Children who live in inadequate environmental conditions are at risk of bacterial overgrowth and methane production.Hydrogen is a substrate for methane production in the colon.

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.

Assessment of small intestinal bacterial overgrowth in uncomplicated acute diverticulitis of the colon

AIM: Small intestinal bacterial overgrowth (SIBO) maycontribute to the appearance of several gastrointestinal nonspecific symptoms. Acute diverticulitis is affected by some similar symptoms and bacterial colonic overgrowth. We assessed the prevalence of SIBO in acute uncomplicated diverticulitis and evaluated its influence on the clinical course of the disease.METHODS: We studied 90 consecutive patients (39 males, 51 females, mean age 67.2 years, range 32-91 years). Sixty-one patients (67.78%) and 29 patients (32.22%) were affected by constipation-or diarrhea-prevalent diverticulitis respectively. All subjects were investigated by lactulose H2-breath test at the entry and at the end of treatment. We also studied a control group of 20 healthy subjects (13 males, 7 females, mean age 53 years, range 22-71 years).RESULTS: Oro-cecal transit time (OCTT) was delayed in67/90 patients (74.44%) (range 115-210 min, mean 120 min). Fifty-three of ninety patients (58.88%) showed SIBO, while OCTT was normal in 23/90 patients (25, 56%). In the control group, the mean OCTT was 88.2 min (range 75-135 min). The difference between diverticulitic patients and healthy subjects was statistically significant (P＜0.01). OCTT was longer in constipation-prevalent disease than in diarrheaprevalent disease [180.7 min (range 150-210 min) vs 121 min (range 75-180 min) (P＜0.001)], but no difference in bacterial overgrowth was found between the two forms of diverticulitis.After treatment with rifaximin plus mesalazine for 10 d, followed by mesalazine alone for 8 wk, 70 patients (81.49%) were completely asymptomatic, while 16 patients (18.60%) showed only slight symptoms. Two patients (2.22%) had recurrence of diverticulitis, and two other patients (2.22%) were withdrawn from the study due to side-effects. Seventy-nine of eighty-six patients (91.86%) showed normal OCTT (range 75-105 min, mean 83 min), while OCTT was longer, but it was shorter in the remaining seven (8.14%) patients (range 105-115 min, mean of 110 min). SIBO was eradicated in all patients, while it persisted in one patient with recurrence of diverticulitis. CONCLUSION: SIBO affects most of the patients with acute diverticulitis. SIBO may worsen the symptoms of patients and prolong the clinical course of the disease, as confirmed in the case of persistence of SIBO and diverticulitis recurrence. In this case, we can hypothesize that bacteria from small bowel may re-colonize in the colon and provoke recurrence of symptoms.

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.

Ileocecal valve dysfunction in small intestinal bacterial overgrowth: A pilot study

AIM: To explore whether patients with a defective ileocecal valve (ICV)/cecal distension reflex have small intestinal bacterial overgrowth. METHODS: Using a colonoscope, under conscious sedation, the ICV was intubated and the colonoscope was placed within the terminal ileum (TI). A manometry catheter with 4 pressure channels, spaced 1 cm apart, was passed through the biopsy channel of the colonoscope into the TI. The colonoscope was slowly withdrawn from the TI while the manometry catheter was advanced. The catheter was placed across the ICV so that at least one pressure port was within the TI, ICV and the cecum respectively. Pressures were continuously measured during air insufflation into the cecum, under direct endoscopic visualization, in 19 volunteers. Air was insufflated to a maximum of 40 mmHg to prevent barotrauma. All subjects underwent lactulose breath testing one month after the colonoscopy. The results of the breath tests were compared with the results of the pressures within the ICV during air insufflation. RESULTS: Nineteen subjects underwent colonoscopy with measurements of the ICV pressures after intubation of the ICV with a colonoscope. Initial baseline readings showed no statistical difference in the pressures of the TI and ICV, between subjects with positive lactulose breath tests and normal lactulose breath tests. The average peak ICV pressure during air insufflation into the cecum in subjects with normal lactu-lose breath tests was significantly higher than cecal pressures during air insufflation (49.33 ± 7.99 mmHg vs 16.40 ± 2.14 mmHg, P = 0.0011). The average percentage difference of the area under the pressure curve of the ICV from the cecum during air insufflations in subjects with normal lactulose breath tests was significantly higher (280.72% ± 43.29% vs 100% ± 0%, P = 0.0006). The average peak ICV pressure during air insufflation into the cecum in subjects with positive lactulose breath tests was not significantly different than cecal pressures during air insufflation 21.23 ± 3.52 mmHg vs 16.10 ± 3.39 mmHg. The average percentage difference of the area under the pressure curve of the ICV from the cecum during air insufflation was not significantly different 101.08% ± 7.96% vs 100% ± 0%. The total symptom score for subjects with normal lactulose breath tests and subjects with positive lactu-lose breath tests was not statistically different (13.30 ± 4.09 vs 24.14 ± 6.58). The ICV peak pressures during air insufflations were significantly higher in subjects with normal lactulose breath tests than in subjects with positive lactulose breath tests (P = 0.005). The average percent difference of the area under the pressure curve in the ICV from cecum was significantly higher in subjects with normal lactulose breath tests than in subjects with positive lactulose breath tests (P = 0.0012). Individuals with positive lactulose breath tests demonstrated symptom scores which were significantly higher for the following symptoms: not able to finish normal sized meal, feeling excessively full after meals, loss of appetite and bloating. CONCLUSION: Compared to normal, subjects with a positive lactulose breath test have a defective ICV cecal distension reflex. These subjects also more commonly have higher symptom scores.

Seventy-five gram glucose tolerance test to assess carbohydrate malabsorption and small bowel bacterial overgrowth

AIM： To investigate non-invasively the incidence of absorption of carbohydrates in diabetic patients during an oral glucose tolerance test （OGTT） and to determine whether malabsorption may be associated with insulin secretion and insulin resistance. METHODS： A standard 75-g OGTT was performed in 82 diabetic patients. The patients received 75 g of anhydrous glucose in 225 mL of water after an overnight fasting and breath samples were collected at baseline and up to 120 rain after ingestion. Breath hydrogen and methane concentrations were measured. Blood glucose and serum insulin concentrations were measured before ingestion and at 30, 60, 90, 120 rain post-ingestion. RESULTS： When carbohydrate malabsorption was defined as subjects with an increase of at least 10 ppm （parts per million） in hydrogen or methane excretion within a 2-h period, 28 （34%） had carbohydrate malabsorption. According to the result of increased breath test, 21 （75%） patients were classified as small bowel bacterial overgrowth and 7 （25%） as glucose malabsorption. Patients with carbohydrate malabsorption were older and had poor glycemic control as compared with those without carbohydrate malabsorption. The HOMA value, the sum of serum insulin during the test and the AinsulinlAglucose ratio were greater in patients with carbohydrate malabsorption. CONCLUSION： Insulin resistance may be overestimated by using these markers if the patient has carbohydrate malabsorption, or that carbohydrate malabsorption may be present prior to the development of insulin resistance. Hence carbohydrate malabsorption should be taken into account for estimating insulin resistance and β-cell function.

Association between small intestinal bacterial overgrowth and deep vein thrombosis

Objective:Small intestinal bacterial overgrowth(SIBO)has been associated with several diseases.The association between SIBO and deep vein thrombosis(DVT)has not been investigated.This study was aimed to investigate the frequency and risk factors for the development of DVT in patients tested for SIBO.Methods:All 321 eligible patients were included from the Cleveland Clinic Gastrointestinal Motility Lab databank from January 2008 to January 2014.Patients who were evaluated with glucose hydrogen/methane breath test as well as Doppler ultrasonography for suspected DVT were included.Patients with catheter-related DVT were excluded.The primary outcomes were the frequency and risk factors(including SIBO)for DVT in this patient population.Results:Of the 321-case cohort,144 patients(44.9%)tested positive for SIBO,and 53(16.5%)had ultrasonographic findings of DVT.SIBO evaluation before the evaluation of DVT occurred in 201 patients(median time from the breath test to ultrasonography:27 months;interquartile range[IQR]:11.0–45.0 months),and SIBO evaluation after evaluation for DVT occurred in 120 patients(median time from ultrasonography to the breath test:30 months;IQR:11.8–54.3 months).In the univariate analysis,DVT was associated with family history of thromboembolic events(35.8%vs 16.0%,P=0.001),chronic kidney diseases(CKD;26.4%vs 13.4%,P=0.019)and the presence of SIBO(69.8%vs 39.9%,P50.001).In themultivariate analysis,family history of thromboembolic events(odds ratio[OR]:3.39;95%confidence interval[CI]:1.67–6.87;P50.001),CKD(OR:2.23;95%CI:1.04–4.74;P=0.037),and the presence of SIBO(OR:3.27;95% CI:1.70–6.32;P50.001)remained independently associated with DVT.Conclusion:SIBO was found to be associated with DVT.The nature of this association warrants further investigation.

Microbiota and the gut-liver axis:Bacterial translocation,inflammation and infection in cirrhosis

Liver disease is associated with qualitative and quantitative changes in the intestinal microbiota. In cirrhotic patients the alteration in gut microbiota is characterized by an overgrowth of potentially pathogenic bacteria (i.e., gram negative species) and a decrease in autochthonous familiae. Here we summarize the available literature on the risk of gut dysbiosis in liver cirrhosis and its clinical consequences. We therefore described the features of the complex interaction between gut microbiota and cirrhotic host, the so called &#x0201c;gut-liver axis&#x0201d;, with a particular attention to the acquired risk of bacterial translocation, systemic inflammation and the relationship with systemic infections in the cirrhotic patient. Such knowledge might help to develop novel and innovative strategies for the prevention and therapy of gut dysbiosis and its complication in liver cirrhosis.

Overgrowth of the indigenous gut microbiome and irritable bowel syndrome

Culture-independent molecular techniques have demonstrated that the majority of the gut microbiota is uncultivable.Application of these molecular techniques to more accurately identify the indigenous gut microbiome has moved with great pace over recent years,leading to a substantial increase in understanding of gut microbial communities in both health and a number of disorders,including irritable bowel syndrome(IBS).Use of culture-independent molecular techniques already employed to characterise faecal and,to a lesser extent,colonic mucosal microbial populations in IBS,without reliance on insensitive,traditional microbiological culture techniques,has the potential to more accurately determine microbial composition in the small intestine of patients with this disorder,at least that occurring proximally and within reach of sampling.Current data concerning culture-based and culture-independent analyses of the small intestinal microbiome in IBS are considered here.

Gut-liver axis and probiotics: Their role in non-alcoholic fatty liver disease

The incidence of obesity and its related conditions, including non-alcoholic fatty liver disease (NAFLD), has dramatically increased in all age groups worldwide. Given the health consequences of these conditions, and the subsequent economic burden on healthcare systems, their prevention and treatment have become major priorities. Because standard dietary and lifestyle changes and pathogenically-oriented therapies (e.g., antioxidants, oral hypoglycemic agents, and lipid-lowering agents) often fail due to poor compliance and/or lack of efficacy, novel approaches directed toward other pathomechanisms are needed. Here we present several lines of evidence indicating that, by increasing energy extraction in some dysbiosis conditions or small intestinal bacterial overgrowth, specific gut microbiota and/or a &#x0201c;low bacterial richness&#x0201d; may play a role in obesity, metabolic syndrome, and fatty liver. Under conditions involving a damaged intestinal barrier (&#x0201c;leaky gut&#x0201d;), the gut-liver axis may enhance the natural interactions between intestinal bacteria/bacterial products and hepatic receptors (e.g., toll-like receptors), thus promoting the following cascade of events: oxidative stress, insulin-resistance, hepatic inflammation, and fibrosis. We also discuss the possible modulation of gut microbiota by probiotics, as attempted in NAFLD animal model studies and in several pilot pediatric and adult human studies. Globally, this approach appears to be a promising and innovative add-on therapeutic tool for NAFLD in the context of multi-target therapy.