Lactulose Hydrogen Breath Test Research Articles

A change in the gut microbiota composition in patients with chronic heart failure and small bacterial overgrowth syndrome

A change in the gut microbiota composition is a risk factor for the development and progression of a number of socially significant diseases. Thus, the prevalence of small bacterial overgrowth syndrome (SBOS) in patients with chronic heart failure CHF) is 38.2–42.0%, as shown by different data, which greatly exceeds that among the persons without CHF. SBOS in CHF is associated with the higher risk of long-term complications (hospitalization and death). Objective. To study the qualitative changes in the large bowel gut microbiota in patients with CHF and SBOS. Subjects and methods. The investigation enrolled 60 patients with CHF and a left ventricular ejection fraction of <50%, as evidenced by echocardiography (after Simpton), who had undergone lactulose hydrogen breath test for the diagnosis of SBOS. According to the test results, the patients were divided into 2 groups; 1) 25 patients with SBOSs; 2) 25 patients without SBOS. In both groups, sequencing of 165 ribosomal RNA was used to study gut microbiota in the fecal samples. Results. Group 1 displayed a decrease in the Shannon index when calculated by bacterial types as compared with that in Group 2 (0.61 [0.49; 0.72] and 0.75 [0.58; 0.86], respectively; p=0.03). Group 1 also exhibited lower levels of the representatives of the Verrucomicrobia type as compared with Group 2 (0.21 [0.00; 4.03] and 2.61 [0.95; 8.02]%, respectively; p=0.05), in particular the Verrucomicrobiaceae family (0.21 [0.00; 4.03] and 2.61 [0.50; 8.42]%, respectively; p=0.05). The decreased level of the representatives of the Verrucomicrobiaceae family in patients with SBOS (Group 1) was due to the lower levels of the representatives of the Akkermansia genus (p=0.05), the only identified representative of which in this study was Akkermansia muciniphila; there were also decreased levels of the representatives of the Desulfovibrio genus (p=0.01), an increase in the representatives of the Dorea genus (p=0.005), as well as those presented in a small number of patients of Papillibacter (p = 0.02), Coprobacillus (p=0.02), Oribacterium (p=0,02), Clostridium cluster XVIII (p=0.05), Slackia genera (p=0.01). In addition, there were lower levels of the representatives of the the Dorea genus (p=0.005), as well as those presented in a small number of patients of Papillibacter (p = .0.02), Coprobacillus (p=0.02), Oribacterium (p=0,02), Clostridium cluster XVIII (p=0.05), Slackia genera (p=0.01).

Small Intestinal Bacterial Overgrowth Is Associated with Poor Prognosis in Cirrhosis.

Small intestinal bacterial overgrowth (SIBO) is associated with numerous manifestations of cirrhosis. To determine whether the presence of SIBO affects the prognosis in cirrhosis was the aim of the study. This prospective cohort study included 50 patients. All participants underwent a lactulose hydrogen breath test for SIBO. The follow-up period was 4 years. SIBO was detected in 26 (52.0%) patients: in 10 (52.6%) patients with compensated cirrhosis and in 16 (51.6%) ones with decompensated cirrhosis. Twelve (46.2%) patients with SIBO and four (16.7%) patients without SIBO died within 4 years (p = 0.009). Among patients with decompensated cirrhosis, 8 (50.0%) patients with SIBO and 3 (20.0%) patients without SIBO died (p = 0.027). Among patients with compensated cirrhosis, four (40.0%) patients with SIBO and one (11.1%) patient without SIBO died (p = 0.045). Among patients with SIBO, there was no difference in mortality between patients with compensated and decompensated cirrhosis (p = 0.209). It was the same for patients without SIBO (p = 0.215). SIBO affects the prognosis only in the first year of follow-up in decompensated cirrhosis, and only in subsequent years in compensated cirrhosis. Presence of SIBO (p = 0.028; HR = 4.2(1.2-14.9)) and serum albumin level (p = 0.027) were significant independent risk factors for death in cirrhosis. SIBO is associated with poor prognosis in cirrhosis.

Impact of Saccharomyces boulardii CNCM I-745 on Bacterial Overgrowth and Composition of Intestinal Microbiota in Diarrhea-Predominant Irritable Bowel Syndrome Patients: Results of a Randomized Pilot Study

Background: Small intestinal bacterial overgrowth (SIBO) is associated with diarrhea-predominant irritable bowel syndrome (IBS-D). Probiotics like Saccharomyces boulardii CNCM I-745 (Sb) may be efficacious in balancing the microbiota. This randomized open label study assessed the effect of Sb in patients with bacterial overgrowth associated with IBS-D and its impact on the intestinal microbiota. Methods: Patients were randomized to receive Sb + dietary advice (Sb + DA) or dietary advice (DA) only for 15 days. SIBO was assessed by the lactulose hydrogen breath test (LHBT). Symptoms were assessed with the IBS Symptom Severity Scale (IBS-SSS) and stool consistency with the Bristol Stool Form Scale. Microbiota and mycobiota were analyzed by 16S rDNA and ITS2. Results: 54 patients were included, among whom 48 (27 Sb + DA, 21 DA) were evaluated. Decrease of hydrogen excretion was slightly higher in Sb + DA group, 41% versus 29% in DA group, and IBS-SSS total score were reduced by −134 and −93, respectively. The proportion of patients with diarrhea was lower in the Sb + DA group than in the DA group (25.9% compared to 47.6%). Bacterial and fungal microbiota showed that Sb treatment was associated with several modifications. Interestingly, F. prausnitzii was more abundant in Sb-treated patients with marked clinical improvement. The safety of S. boulardii CNCM I-745 was excellent. Conclusions: In patients with SIBO, S. boulardii CNCM I-745 associated with dietary advice reduced bacterial overgrowth and improved digestive symptoms while restoring the intestinal microbiota. The increased abundance of F. prausnitzii coupled with symptom improvement merits further research.

Exhaled Hydrogen after Lactulose Hydrogen Breath Test in Patient with Duodenal Ulcer Disease-A Pilot Study for Helicobacter-pylori-Associated Gastroduodenal Disease.

The precipitating mechanism(s) from the inactive to the active stage of duodenal ulcer disease (DU) is unclear. It has been shown that hydrogen gas from colonic fermentation provides an important energy source for Helicobacter pylori (Hp) colonization. The lactulose hydrogen breath test (LHBT) is a useful tool to assess the small intestinal and/or colon fermentation. This study examines the association(s) between the status of gastroduodenal disease and the result of a lactulose hydrogen breath test (LHBT). We enrolled Hp-positive active duodenal ulcer (aDU) patients, inactive DU (iDU) patients and patients with a positive Hp infection without structural gastroduodenal lesion, i.e., simple gastritis (SG Hp+). The patients with simple gastritis without Hp infection (SG Hp-) served as controls. Histological examinations of the gastric mucosa and lactulose hydrogen breath test (LHBT) were performed. SG Hp+ patients tend to have advanced gastritis (pangastritis or corpus-predominant gastritis) compared with SG Hp- patients (7/29 vs. 0/14, p = 0.08). More iDU patients had advanced gastritis than either the SG Hp+ (7/9 vs. 7/29, p = 0.006) or aDU patients (7/9 vs. 6/24, p = 0.013). In comparison with the aDU patients, the iDU patients were also older (52.1 ± 12.6 vs. 42.2 ± 11.9 years, p = 0.02) and had a lower mean area under the curve value of the LHBT(AUC) (209.1 ± 86.0 vs. 421.9 ± 70.9, p = 0.023). aDU patients with a positive Hp infection have a lower grade of gastric mucosa damage than iDU patients and tend to have a higher level of exhaled hydrogen after LHBT.

Association of serotonin transporter promoter polymorphism (5-HTTLPR) with orocecal transit time in irritable bowel syndrome.

Irritable bowel syndrome (IBS) is a multifactorial disorder with altered intestinal motility, secretion, and sensation. Serotonin (5-HT) stimulates gut motility and alters serotonin signaling that may lead to both intestinal and extraintestinal symptoms in IBS. The aim of this study was to examine the association of serotonin transporter gene promoter polymorphism (5-HTTLPR) in IBS with orocecal transit time (OCTT) measured by lactulose hydrogen breath test. This prospective case-control study included 151 IBS patients (mean±SD 37.4±11.6 years, median 36, range 19-68). Ninety-two patients were diarrhea-predominant IBS (D-IBS), 44 constipation-predominant IBS (C-IBS), 15 alternating diarrhea and constipation IBS (M-IBS), and 100 healthy controls (mean±SD 37.2±11.4 years, median 36, range 20-64 years). 5-HTTLPR gene polymorphism was studied by polymerase chain reaction-based method. 5-HT levels were measured by enzyme-linked immunosorbent assay (ELISA). Orocecal transit time (OCTT) was measured by a non-invasive lactulose hydrogen breath test. OCTT was also compared with respect to 5-HTTLPR genotypes in differentIBS phenotypes. Serum serotonin levels were significantly higher in overall IBS patients (152±77 ng/mL, p<0.001), D-IBS (184±76 ng/mL, p<0.001), compared to healthy controls (129±56 ng/mL). There was no difference in 5-HT levels between C-IBS (124±53 ng/mL) and controls. In the case of M-IBS, 5-HT levels were (88±49 ng/mL p<0.05) significantly lower than that of controls. OCTT was significantly shorter in D-IBS patients (95±36 min) as compared to controls (112±41 min). In contrast, C-IBS showed significantly prolonged OCTT (136±54 min). There was a significant difference in OCTT between D-IBS and C-IBS patients (p<0.001). There was no significant association found between OCTT and 5-HTTLPR. Serum serotonin concentrations were increased in D-IBS compared to controls and C-IBS. OCTT was shorter in D-IBS and delayed in C-IBS patients. There was no association of 5-HTLPR polymorphism with OCTT.

Low-FODMAP Diet for the Management of Irritable Bowel Syndrome in Remission of IBD.

Approximately 30% of patients with quiescent inflammatory bowel disease (IBD) meet the diagnostic criteria for irritable bowel syndrome (IBS). The aim of this study was to evaluate the effectiveness of a low-FODMAP diet in patients who meet the diagnostic criteria for IBS whilst in IBD remission. A total of 200 patients in remission of IBD were included in the study. Sixty-five of these patients (32.5%) were diagnosed with IBS according to the R4DQ. On the patients who met the IBS diagnostic criteria, anthropometric measurements, laboratory tests and lactulose hydrogen breath tests were performed. A low-FODMAP diet was introduced for 6 weeks. Of the 59 patients with IBS diagnosed at baseline for whom data were collected at the end of follow-up, after the low-FODMAP intervention IBS-like symptoms were not present in 66.1% (n = 39) (95% CI (53.4%; 76.9%)). The difference between the two groups (with SIBO at baseline (33 of 48 patients) and without SIBO at baseline (6 of 11 patients)) in the low-FODMAP diet's effectiveness was not statistically significant (p = 0.586). The low-FODMAP diet improved the gut symptoms of flatulence and diarrhea. It had no effect on the occurrence of constipation. In IBD patients in remission who meet the IBS criteria, the dietary intervention of a low-FODMAP diet is effective for a reduction in IBS-like symptoms, regardless of the coexistence of bacterial overgrowth.

Antimicrobial treatment improves tryptophan metabolism and mood of patients with small intestinal bacterial overgrowth

BackgroundOptimal composition of intestinal bacteria is an essential condition for good health. Excessive growth of these bacteria can cause various ailments. The aim of this study was to assess the mental state and gastrointestinal complaints of patients with small intestinal bacterial overgrowth (SIBO) in relation to tryptophan metabolism and rifaximin treatment.Methods120 subjects, aged 23–61 years, were enrolled in the study, and divided into 3 groups, 40 individuals each: healthy subjects (Controls), patients with SIBO and chronic diarrhea (SIBO-D), and with chronic constipation (SIBO-C). The lactulose hydrogen breath test (LHBT) was performed to diagnose SIBO. The mental state of patients was assessed using the Hamilton Anxiety Rating Scale (HAM-A), and the Hamilton Depression Rating Scale (HAM-D). L-tryptophan (TRP) and its metabolites: 5-hydroxyindoleacetic acid (5-HIAA), kynurenine (KYN), xanthurenic acid (XA) and quinolinic acid (QA) were measured in urine by liquid-chromatography-tandem mass spectrometry and related to creatinine level. Patients with SIBO were recommended to take rifaximin for 10 days at daily dose 1200 mg, and this cycle was repeated in subsequent two months.ResultsMild and moderate anxiety, as well as mild depression were diagnosed in all SIBO patients. Changes in TRP metabolism were also observed in these patients. Specifically, an increase in the activity of the serotonin pathway of TRP metabolism in the group SIBO-D was observed. The SIBO-C patients showed an increase in the concentration of KYN, XA and QA. 5-HIAA/TRP and KYN/TRP ratios significantly decreased in group SIBO-D, and KYN and QA levels decreased in group SIBO-C after treatment with rifaximin. The levels of anxiety and depression decreased in both groups.ConclusionRifaximin treatment of SIBO patients ameliorated their mood disorders and gastrointestinal aliments underlined by changes in tryptophan metabolism.Trial registration Retrospectively registered (if applicable).

Altered Tryptophan Metabolism on the Kynurenine Pathway in Depressive Patients with Small Intestinal Bacterial Overgrowth.

The causes of depression are diverse and are still not fully understood. Recently, an increasing role is attributed to nutritional and inflammatory factors. The aim of this study was to evaluate selected metabolites of the tryptophan kynurenine pathway in depressive patients with small intestinal bacterial overgrowth (SIBO). The study involved 40 healthy people (controls) and 40 patients with predominant small intestinal bacterial overgrowth (SIBO-D). The lactulose hydrogen breath test (LHBT) was performed to diagnose SIBO. The severity of symptoms was assessed using the Gastrointestinal Symptom Rating Scale (GSRS–IBS) and the Hamilton Depression Rating Scale (HAM-D). The concentration of tryptophan (TRP), kynurenine (KYN), kynurenic acid (KYNA), and quinolinic acid (QA) in urine was determined using an LC–MS/MS method, before and after cyclic treatment with an antibiotic drug, rifaximin, for three months. The number of intraepithelial lymphocytes (IELs) in the duodenum and small intestinal mucosa, fecal calprotectin (FC) and serum level of C-reactive protein (CRP) were also determined. In patients with SIBO, a higher level of KYN and QA were found as compared to the control group. These two groups also differed in KYN/TRP (higher in SIBO) and KYNA/KYN ratios (lower in SIBO). A positive correlation was found between HAM-D and the number of IELs and the level of FC. Treatment with rifaximin improves the kynurenic pathway, as well as abdominal and mental complaints. Therefore, small intestinal bacterial overgrowth can be a cause of abdominal symptoms, but also mental disorders.

Probiotic Saccharomyces boulardii in the Treatment of Small Intestinal Bacterial Overgrowth in Decompensated Cirrhosis

ObjectivesSmall intestinal bacterial overgrowth (SIBO) is often detected in cirrhosis and is associated with the development of a number of its complications. Currently, there is no data on the effectiveness of drugs in the treatment of this disorder in this disease. The aim of the study was to evaluate the efficacy of probiotic Saccharomyces boulardii in the treatment of SIBO in cirrhosis.MethodsThis was a study in which 37 patients with decompensated cirrhosis and SIBO were randomized into 2 groups in a ratio of 1.5 to 1. The probiotic group included 24 patients who received probiotic Saccharomyces boulardii at a dose of 250 mg 2 times a day for 3 months in addition to standard therapy. The control group included 13 patients who received placebo for 3 months in addition to standard therapy. The use of antibiotics was prohibited. The patients were blinded. The presence of SIBO was assessed on the basis of a lactulose hydrogen breath test.ResultsThe mean age of the included patients was 50.5 ± 9.9 years. There were 14 men and 23 women. Cirrhosis was alcoholic in 19 cases, viral in 5 cases, metabolic in 2 cases, mixed etiology in 7 cases, cryptogenic in 4 cases. After 3 months of probiotic or placebo use, SIBO was detected in 4 (16.7%) patients in the probiotic group and in 10 (76.9%) patients in the control group (P = 0.001). Moreover, the incidence of ascites in the probiotic group decreased from 83.3% to 45.8% (P = 0.007) and did not change significantly in the placebo group (69.2% vs. 84.6%; P = 0.007). No adverse effects of probiotics or placebo use were reported.ConclusionsProbiotic Saccharomyces boulardii is effective and safe in the treatment of SIBO in decompensated cirrhosis.Funding SourcesSupported by BIOCODEX MICROBIOTA FOUNDATION: National Research Grant Russia 2019.

Gastric Fermentation in Functional Dyspepsia

Background: The role of the gastric fermentation in functional dyspepsia has been investigated. Methods: Lactulose Hydrogen Breath test, H. pylori 13C Urea Breath Test. 47 patients with functional dyspepsia (FD) has been investigated. Results: Positives for lactulose hydrogen breath test 23, negatives 24. H. pylori and hydrogen breath test positives 12.

Efficacy of Pro-Kinetic Agents in Type 2 Diabetes Mellitus Patients With Gastroparesis Using Lactulose Hydrogen Breath Testing: A Randomized Trial.

AimThe aim of the study was to determine the efficacy of prokinetic agents in diabetic gastroparesis patients.MethodThis was a randomized open-label trial conducted on 50 patients with type 2 diabetes experiencing diabetic gastroparesis, which was diagnosed with the lactulose hydrogen breath test. After randomization, all 50 patients were divided into four arms (cinitapride, metoclopramide, levosulpiride, and domperidone) of different prokinetics and followed up for four weeks; after which, repeat gastroparesis cardinal symptom index score and orocecal transit time were recorded in order to assess the response to the treatment.ResultThere was no statistically significant difference among the four groups in terms of all the baseline characteristics except for gender (p=0.032). The follow-up gastroparesis cardinal symptom index was collected for 50 patients but repeat orocecal transit time could be performed only in 37 patients. In all four groups, there was a statistically significant (p<0.05) improvement in terms of orocecal transit time and gastroparesis cardinal symptom index scores. But there was no statistically significant difference in relative efficacy amongst these study groups.ConclusionOur study showed statistically significant improvement with four prokinetics drugs in terms of gastroparesis cardinal symptom index score and orocecal transit time, but there was no statistically significant benefit of one prokinetic drug over the other. Our study showed promising results with regard to prokinetic use in diabetic gastroparesis.

Особенности течения синдрома раздраженного кишечника при присоединении синдрома избыточного бактериального роста

Aim: to assess the rate and pattern of the clinical course of small intestinal bacterial overgrowth (SIBO) in irritable bowel syndrome (IBS). Patients and Methods: this study enrolled 100 patients aged 18–68 (mean age 33.5 [26; 46.25] years) with established IBS. The patients were divided into two groups. The IBS with diarrhea (IBS+D) group included 54 patients (mean age 36 [23.0; 49.5] years). The IBS without diarrhea (IBS–D) group included 46 patients (mean 37 [24.5; 49.5] years). All patients underwent lactulose hydrogen breath test using Gastroplus+ monitor to establish SIBO. A positive lactulose hydrogen breath test (a rise of ≥ 20 ppm by 90 min with dual-peak profile or a steady growth of ≥ 12 ppm from baseline in hydrogen) suggested SIBO. Medical history, clinical and lab tests, and the parameters of the quality of life (QoL) using SF-36 and QOL questionnaires were evaluated. Results: the occurrence of SIBO in patients with IBS was 32%, i.e., 37% in the IBS+D group and 28% in the IBS–D group. Multivariate analysis has demonstrated that flatulence in IBS increases the chances of having SIBO by 110.9 times. Univariate analysis revealed universal clinical associations of SIBO with bloating, flatulence, nausea, weakness, tearfulness, and irritability in IBS. Hepatic steatosis is typical for IBS with SIBO (OR=1.75, 95% CI 1.01–3.99, p=0.037). The use of loperamide in IBS+D is associated with a 2.2-fold increase in SIBO risk. SIBO in IBS is associated with a reduction in QoL, as demonstrated by most SF-36 scales (physical and emotional health) and QOL. Conclusions: SIMO in IBS mimics exacerbation, thereby resulting in the prescription of inadequate treatment. KEYWORDS: irritable bowel syndrome, small intestinal bacterial overgrowth, hydrogen respiratory test, quality of life. FOR CITATION: Kulygina Yu.A., Osipenko M.F. Course of irritable bowel syndrome associated with small intestinal bacterial overgrowth. Russian Medical Inquiry. 2022;6(5):232–236 (in Russ.). DOI: 10.32364/2587-6821-2022-6-5-232-236.

Особенности микробиоты у пациентов с болезнью Крона в зависимости от наличия синдрома избыточного бактериального роста

Aim: to evaluate microbiota in Crohn’s disease depending on the presence/absence of small intestinal bacterial overgrowth (SIBO). Patients and Methods: thirteen patients with Crohn’s disease affecting the small intestine were enrolled. Gut microbiota composition was analyzed using the 16S rRNA gene sequencing. 16S rDNA clone libraries were generated similarly. All patients underwent lactulose hydrogen breath test using Gastroplus+ monitor to establish SIBO. A positive lactulose hydrogen breath test indicated SIBO. Results: hydrogen breath test revealed SIBO in 8 patients with Crohn’s disease affecting the small intestine (61.5%). All these patients were women (mean age 40.5 [34.5; 51.2] years). In 5 patients (mean age 32.4 [28.7; 36.5] years), SIBO was not detected. The metagenome analysis of intestinal bacteria identified certain significant differences in microbiota composition in patients with Crohn’s disease depending on the presence/absence of SIBO. In Crohn’s disease affecting the small intestine, SIBO was associated with greater occurrence of Chryseobacterium spp. (р=0.045), Klebsiella spp. (р=0.045), Phocaecola operational taxonomic unit (OTU) (р=0.045), Enterobacteriaceae OTU (р=0.045), Pasteurellales. (р=0.031), Peptoniphilaceae (р=0,023), Solobacterium spp. (р=0.002), Haemophilus spp. (р=0.031), Lachnospiracea OTU (р=0.045), and Bifidobacterium spp. (р=0.019). Conclusions: a taxonomic shift with the reduction of Firmicutes and Bifidobacterium and increase of Proteobacteria (i.e., Klebsiella spp. and Enterobacteriaceae OTU) was revealed in patients with Crohn’s disease and SIBO. KEYWORDS: inflammatory bowel disease, Crohn’s disease, microbiota, small intestinal bacterial overgrowth, hydrogen respiratory test. FOR CITATION: Kulygina Yu.A., Osipenko M.F., Alikina T.Yu. Microbiota pattern in Crohn’s disease depending on the presence ofsmall intestinal bacterial overgrowth. Russian Medical Inquiry. 2022;6(5):221–226 (in Russ.). DOI: 10.32364/2587-6821-2022-6-5-221-226.

Small intestinal bacterial overgrowth in Alzheimer\u2019s disease

The results of animal studies and clinical data support the gut microbiota contribution to the pathogenesis of Alzheimer’s disease (AD). The aim of this pilot study was to evaluate the prevalence of small intestinal bacterial overgrowth (SIBO) and fecal markers of intestinal inflammation and permeability in AD patients. The study was conducted in 45 AD patients and 27 controls. Data on comorbidities, pharmacotherapy, and gastrointestinal symptoms were acquired from medical records and a questionnaire. SIBO was evaluated using lactulose hydrogen breath test. Fecal calprotectin and zonulin levels were assessed by ELISA assays. The positive result of SIBO breath test was found in 49% of the AD patients and 22% of the controls (p = 0.025). The comparative analysis between SIBO-positive and SIBO-negative AD patients with respect to the degree of cognitive impairment, comorbidities and used medications did not reveal any statistically significant difference, except for less common heartburn in SIBO-positive AD patients than in SIBO-negative ones (9 vs 35%, p = 0.038). The median fecal calprotectin and zonulin levels in the AD group compared to the control group amounted to 43.1 vs 64.2 µg/g (p = 0.846) and 73.5 vs 49.0 ng/ml (p = 0.177), respectively. In the AD patients there was no association between the presence of SIBO and fecal calprotectin level. Patients with AD are characterized by higher prevalence of SIBO not associated with increased fecal calprotectin level that may be related to anti-inflammatory effect of cholinergic drugs used in the treatment of AD.

Serotonin Pathway of Tryptophan Metabolism in Small Intestinal Bacterial Overgrowth-A Pilot Study with Patients Diagnosed with Lactulose Hydrogen Breath Test and Treated with Rifaximin.

Small intestinal bacterial overgrowth (SIBO) is a condition associated with diverse clinical conditions and there is no gold standard in its diagnosis and treatment. Tryptophan (Trp) metabolism may be involved in etiology of gastrointestinal diseases and is regulated by intestinal microbiota. In our study we investigated aspects of the serotonin (5-HT) pathway of Trp metabolism in three groups of individuals based on the hydrogen concentration in the lactulose hydrogen breath test (LHBT): controls (<20 ppm) and SIBO patients (≥20 ppm), with diarrhea (SIBO-D) or constipation (SIBO-C). The SIBO-D patients showed an increased serum concentration of 5-HT and small intestinal mucosa mRNA expression of tryptophan hydroxylase 1 (TPH-1), a rate-limiting enzyme in 5-HT biosynthesis. Urinary 5-hydroxyindoleacetic acid (5-HIAA), the main metabolite of 5-HT, was higher in both group of SIBO patients than controls. A positive correlation between 5-HIAA and LHBT was observed. A two-week treatment with rifaximin decreased hydrogen in LHBT and 5-HIAA concentration in SIBO patients. In conclusion, the serotonin pathway of Trp metabolism may play a role in the pathogenesis of hydrogen-positive SIBO and it may influence the diversification of SIBO into variants with diarrhea or constipation. As urinary 5-HIAA concentration correlates with LHBT, TPH-1 expression in colonic mucosa and TH-5 in serum of SIBO patients, it can be considered as a non-invasive marker of this condition.

Application of methane and hydrogen-based breath test in the study of gestational diabetes mellitus and intestinal microbes

ObjectiveGestational diabetes mellitus (GDM) is a common complication of pregnancy. The purpose of this study was to compare the incidence of small intestinal bacterial overgrowth (SIBO) in patients with GDM and the control group by methane and hydrogen lactulose breath test (LBT), and to explore its relationship with inflammation, vitamins, and the outcomes of maternal and child. MethodsLBT was detected in 220 GDM patients, 160 pregnancy control patients and 160 pre-pregnancy control patients. The fasting blood glucose, white blood cells, vitamin A, D, E, neonatal weight, neonatal blood glucose and so on were compared and analyzed. ResultsThere was no statistical significance in the general data of the three groups. The proportion of abdominal distension in the GDM group was higher than that in the other two groups (P < 0.001). The positive rates of SIBO + in GDM group, gestational control group and pre-pregnancy control group were 54.55%, 27.50% and 14.38%, respectively. The average abundance of hydrogen and methane in GDM group was significantly higher than that in control group at each time point. In the GDM group, SIBO + subjects had higher levels of fasting blood glucose, glycoglycated hemoglobin, C-reactive protein, neonatal weight, and lower levels of vitamin D and neonatal blood glucose (P < 0.001). ConclusionPatients with GDM have a high incidence of SIBO, and SIBO may further increase their blood glucose by affecting inflammatory response and vitamin level, and even affect the outcome of mother and child.

Small intestinal bacterial overgrowth and orocecal transit time in patients of nonalcoholic fatty liver disease.

The aim of the present study is to explore the frequency of small intestinal bacterial overgrowth (SIBO) and orocecal transit time (OCTT) in patients with nonalcoholic fatty liver disease (NAFLD). 103 patients with NAFLD and 49 healthy controls were enrolled. Clinical indicators such as BMI, liver function, blood lipids, homeostasis model assessment-insulin resistance (HOMA-IR), serum endotoxin of NAFLD patients were collected and examined. FibroTouch was used to detect the controlled attenuation parameter (CAP) and liver stiffness measurement (LSM). SIBO and OCTT were measured by the lactulose hydrogen breath test. The incidence of SIBO in NAFLD patients (58.3%) was significantly higher than that in healthy controls (26.5%). The level of serum endotoxin in NAFLD patients was higher than that in healthy controls. The levels of CAP, LSM, serum endotoxin, alanine transaminase, asperate aminotransferase and HOMA-IR in SBIO-positive NAFLD patients were higher than those in SIBO-negative patients. There was no significant difference in glutamyl transpeptidase triglyceride, low density lipoprotein and BMI between the two groups. OCTT in NAFLD patients was longer than that in healthy controls. It was also observed that OCTT in SIBO-positive NAFLD patients was significantly delayed compared with SIBO-negative NAFLD patients. Patients with NAFLD exhibit the increased incidence rate of SIBO and prolonged OCTT; SIBO in NAFLD patients maybe a contributing factor to the elevated transaminase, hepatic steatosis, progression of liver fibrosis and prolonged OCTT.

Clinical efficacy of fecal microbiota transplantation for patients with small intestinal bacterial overgrowth: a randomized, placebo-controlled clinic study

BackgroundSmall intestinal bacterial overgrowth (SIBO) is characterized by the condition that bacteria overgrowth in the small intestine. Fecal microbiota transplantation (FMT) has been applied as an effective tool for reestablishing the structure of gut microbiota. However, whether FMT could be applied as a routine SIBO treatment has not been investigated.MethodsIn this trial, 55 SIBO patients were enrolled. All participants were randomized in two groups, and were given FMT capsule or placebo capsules once a week for 4 consecutive weeks. Measurements including the lactulose hydrogen breath test gastrointestinal symptoms, as well as fecal microbiota diversity were assessed before and after FMT therapy.ResultsGastrointestinal symptoms significantly improved in SIBO patients after treatment with FMT compared to participants in placebo group. The gut microbiota diversity of FMT group had a significant increase, while placebo group showed none.ConclusionsThis study suggests that applying FMT for patients with SIBO can alleviate gastrointestinal symptoms, indicating that FMT may be a promising and novel therapeutic regimen for SIBO.Trial registryThis study was retrospectively registered with the Chinese Clinical Trial registry on 2019.7.10 (ID: ChiCTR1900024409, http://www.chictr.org.cn).

Adding a liquid test meal to a standardized lactulose hydrogen breath test significantly influences abdominal symptom generation and hydrogen values.

While single sugar tests are controversially discussed, combination tests with meals are gaining more attention. The aim of this study was to analyze the impact of adding a test meal to lactulose hydrogen breath tests (LHBT) on hydrogen values and abdominal symptoms in patients with functional gastrointestinal disorders (FGIDs). Data of 81 FGID patients between 2014-2018 were analyzed. Patients underwent LHBT with 30 g lactulose + 300 mL water and a nutrient challenge test (NCT) including 400 mL liquid test meal + 30 g lactulose. To statistically assess the effect of a test meal on abdominal symptoms and H2, mixed-effect models were used. Adding a test meal to LHBT showed a significant increase in nausea [odds ratio (OR) 1.4; 95% confidence interval (CI), 1.1-1.7], decrease in abdominal pain (OR 0.7; 95% CI, 0.6-0.9), borborygmi (OR 0.5; 95% CI, 0.4-0.6), diarrhea (OR 0.4; 95% CI, 0.3-0.6), and H2 production (estimate -5.3, SE 0.7, P < 0.001). The effect on bloating was only significant in functional dyspepsia, irritable bowel syndrome-functional dyspepsia mixed type and functional abdominal pain/bloating (OR 0.1; 95% CI, 0.0-0.2; OR 1.7; 95% CI, 1.2-2.3 resp OR 4.4; 95% CI, 1.8-10.6). Significant effects on abdominal symptoms and H2 production by adding a test meal to LHBT in FGID patients are shown. Increased occurrence of nausea may be caused by gastric/duodenal hypersensitivity; decreased H2, diarrhea and borborygmi by slower and more physiologic gastric emptying resulting in later arrival of the test substance in the bowel. We recommend NCTs instead of LHBT to more physiologically represent FGID patients' meal-induced burden.

Prevalence and predictors of small intestinal bacterial overgrowth in systemic sclerosis: a systematic review and meta-analysis.

The reported prevalence of small intestinal bacterial overgrowth (SIBO) among patients with systemic sclerosis (SSc) is highly variable. We conducted this systematic review and meta-analysis to estimate the prevalence and identify predictors of SIBO in SSc by summarizing all of the available data. A comprehensive literature search of the PubMed, Cochrane Library, and EMBASE databases from inception to July 2020 was conducted for studies correlating SIBO with SSc. Studies were screened, and relevant data were extracted and analyzed. The pooled prevalence of SIBO among SSc patients and the odds ratio (OR) of SIBO among SSc patients compared with healthy controls were calculated. Furthermore, predictors of SIBO in SSc were evaluated. Fourteen studies containing 700 SSc patients and 217 healthy controls met the inclusion criteria. The pooled prevalence of SIBO in SSc was 34% (95% CI 27-42%). The OR of SIBO in SSc patients was 12.51 (95% CI 6.51-24.03) compared with the healthy controls. Subgroup analyses showed that the prevalence of SIBO in SSc was higher in studies using the lactulose hydrogen breath test (LHBT) for diagnosis (56%, 95% CI 46-67%) compared with those that used the glucose hydrogen breath test (GHBT) (27%, 95%CI 20-35%) and a jejunal aspirated culture (JAC) (35%, 95%CI 25-51%). The prevalence of SIBO in SSc was higher in studies conducted in Western countries (38%, 95% CI 31-47%) than those conducted in Asian countries (15%, 95%CI 10-23%), and the prevalence of SIBO in the SSc population defined by ACR-EULAR 2013 (50%, 95% CI 0.21-0.79) was higher than the prevalence defined by ACR 1980 (30%, 95% CI 0.17-0.42) or other criteria (32%, 95% CI 0.16-0.48) Moreover, the risk of diarrhea was higher in SSc patients with SIBO than those without SIBO (OR 8.82, 95% CI 4.09-19, P < 0.00001); gender, SSc subset, digital ulcer, and pulmonary fibrosis do not seem to be associated with SIBO in SSc. Antibiotic therapy seems to be effective with SIBO in SSc patients. Approximately one-third of SSc patients tested positive for SIBO with a significantly increased risk over the controls. The prevalence of SIBO in SSc varied according to the SIBO diagnostic test performed, geographic area, and SSc diagnostic criteria. The presence of diarrhea may be a predictor of SIBO in SSc. Antibiotic treatment can lead to eradication of SIBO and gastrointestinal symptomatic improvement in SSc patients. Key Points • The pooled prevalence of SIBO in SSc patients was 34%, which varied according to the SIBO diagnostic test performed, geographic area and SSc diagnostic criteria. • The risk of SIBO in SSc was increased by nearly thirteenfold compared to the healthy controls. • Diarrhoea, but not gender, SSc subset, digital ulcer and pulmonary fibrosis, was associated with SIBO in SSc patients. • For SSc patients with SIBO, antibiotic treatment can lead to eradication of SIBO and gastrointestinal symptomatic improvement.