The gut microbiota-constipation connection: Insights from a two sample bidirectional Mendelian randomization study.

OBJECTIVE: The dysbiosis of the gut microbiota has been implicated in various maladies. Research has identified an association between the dysbiosis of the gut microbiota and the risk of constipation, prompting this study to elucidate the potential causal relationship between gut microbiota imbalance with constipation through a two sample bidirectional Mendelian randomization (MR) study, shedding light on the genetic mechanisms underlying the connection between gut microbiota and constipation. METHODS: The forward MR analysis aimed to scrutinize whether alterations in the composition and abundance of gut microbiota impact the risk of constipation, while the reverse MR analysis explored whether the genetic predisposition to constipation influences the abundance of gut microbiota. Genomic correlation data for the gut microbiota were sourced from the comprehensive statistics of the MiBioGen consortium. Genomic correlation data for constipation were obtained from the IEU database, encoded as the dataset ebi-a-GCST90018829. The correlation was assessed using various analytical techniques, including inverse variance weighting (IVW), Mendelian randomization-Egger regression (MR-Egger), and weighted median and mode methodologies. To ensure the robustness of the results, a meticulous sensitivity analysis was conducted, incorporating Cochran's Q test, MR-Egger intercept test, Mendelian Randomization Pleiotropy RESidual Sum and Outlier (MR-PRESSO), and a Leave-one-out analysis. RESULTS: In the forward Mendelian randomization analyses, a negative correlation was discerned between the abundance of Coprococcus in the gut microbiota and the occurrence of constipation (IVW: OR = 0.74, 95 % CI = 0.64-0.86, p = 0.0001), whereas a positive correlation was observed between the abundance of Bacteroidetes in the gut microbiota and constipation (IVW: OR = 1.22, 95 % CI = 1.00-1.50, p = 0.04). In the forward Mendelian randomization analyses, we were unsuccessful in obtaining valid instrumental variables for scrutiny, and we deemed that constipation exerts no influence on the composition of the gut microbiota. CONCLUSION: Genetic predisposition towards increased abundance of Coprococcus and decreased abundance of Bacteroidetes is correlated with a diminished susceptibility to constipation. This investigation showed that alterations in the gut microbiota precipitated the onset of constipation, rather than constipation inducing modifications in the microbial flora.

The causal relationship between gut microbiota and constipation: a two-sample Mendelian randomization study.

BACKGROUND: Constipation is one of the most common gastrointestinal disorders afflicting the population, with recent observational studies implicating dysfunction of the gut microbiota in constipation. Despite observational studies indicating a relationship, a clear causality remains unclear. This study aims to use two-sample Mendelian randomization (MR) to establish a clearer causal relationship between the two. METHODS: A two-sample Mendelian randomization (MR) study was performed using the gut microbiota summary Genome-Wide Association Studies (GWAS) statistics from MiBioGen consortium (n = 13,266) and constipation GWAS summary statistics from the IEU OpenGWAS database. The causality between gut microbiota and constipation is primarily analyzed using the inverse-variance weighted (IVW) method and reinforced by an additional four methods, including MR-Egger, Weighted Median, Simple Mode, and Weighted Mode. Finally, funnel plot, heterogeneity test, horizontal pleiotropy test, and leave-one-out test were used to evaluate the reliability of MR results. RESULTS: IVW estimates suggested that the bacterial species Anaerotruncus, Butyricimonas, and Hungatella were causally associated with constipation. The odds ratio (OR) values of Anaerotruncus, Butyricimonas, and Hungatella were 1.08 (95% CI = 1.02-1.13; P = 0.007), 1.07 (95% CI = 1.01-1.13; P = 0.015), 1.03 (95% CI = 1.00-1.06; P = 0.037) respectively. Meanwhile, Ruminiclostridium 9 and Intestinibacter have been shown to be associated with a reduced risk of constipation. The OR of Ruminiclostridium 9 = 0.75(95% CI = 0.73-0.78, P < 0.001 and Intestinibacter of OR = 0.89 (95% CI = 0.86-0.93, P < 0.001). Furthermore, validation by funnel plot, heterogeneity test, and horizontal pleiotropy test showed that MR results were reliable. CONCLUSION: This is the first Mendelian randomization study to explore the causalities between specific gut microbiota taxa and constipation, and as such may be useful in providing insights into the unclear pathology of constipation which can in turn aid in the search for prevention and treatment.

Hydrogen Sulfide Producers Drive a Diarrhea-Like Phenotype and a Methane Producer Drives a Constipation-Like Phenotype in Animal Models.

BACKGROUND: We recently demonstrated that diarrhea-predominant irritable bowel syndrome (IBS-D) subjects have higher relative abundance (RA) of hydrogen sulfide (H2S)-producing Fusobacterium and Desulfovibrio species, and constipation-predominant IBS (IBS-C) subjects have higher RA of methanogen Methanobrevibacter smithii. AIMS: In this study, we investigate the effects of increased methanogens or H2S producers on stool phenotypes in rat models. METHODS: Adult Sprague-Dawley rats were fed high-fat diet (HFD) for 60 days to increase M. smithii levels, then gavaged for 10 days with water (controls) or methanogenesis inhibitors. To increase H2S producers, rats were gavaged with F. varium or D. piger. Stool consistency (stool wet weight (SWW)) and gas production were measured. 16S rRNA gene sequencing was performed on stool samples. RESULTS: In HFD diet-fed rats (N = 30), stool M. smithii levels were increased (P < 0.001) after 52 days, correlating with significantly decreased SWW (P < 0.0001) at 59 days (R = - 0.38, P = 0.037). Small bowel M. smithii levels decreased significantly in lovastatin lactone-treated rats (P < 0.0006), and SWW increased (normalized) in lovastatin hydroxyacid-treated rats (P = 0.0246), vs. controls (N = 10/group). SWW increased significantly in D. piger-gavaged rats (N = 16) on day 10 (P < 0.0001), and in F. varium-gavaged rats (N = 16) at all timepoints, vs. controls, with increased stool H2S production. 16S sequencing revealed stool microbiota alterations in rats gavaged with H2S producers, with higher relative abundance (RA) of other H2S producers, particularly Lachnospiraceae and Bilophila in F. varium-gavaged rats, and Sutterella in D. piger-gavaged rats. CONCLUSIONS: These findings suggest that increased M. smithii levels result in a constipation-like phenotype in a rat model that is partly reversible with methanogenesis inhibitors, whereas gavage with H2S producers D. piger or F. varium results in increased colonization with other H2S producers and diarrhea-like phenotypes. This supports roles for the increased RA of methanogens and H2S producers identified in IBS-C and IBS-D subjects, respectively, in contributing to stool phenotypes.

Effect of Lactobacillus reuteri NCIMB 30351 drops on symptoms of infantile functional gastrointestinal disorders and gut microbiota in early infants: Results from a randomized, placebo-controlled clinical trial.

Infantile functional gastrointestinal disorders, such as colic, constipation, diarrhea, and gastroesophageal reflux (regurgitation), often occur in early infancy and, representing one of the causes of significant parental anxiety, lead to a significant strain on the healthcare resources. In this study, we aimed to evaluate the effects of Lactobacillus reuteri drops (L. reuteri NCIMB 30351) on the symptoms of infantile colic, constipation, diarrhea, and gastroesophageal reflux, as well as on the levels of intestinal microbiota in full-term newborns during the first months of life. A randomized, placebo-controlled, single-masked (blinded), post-marketing clinical study was conducted in two clinical units-Children's City Clinical Hospital of Moscow and Medical Center "St. Andrew's Hospitals-NEBOLIT" from March 2020 to May 2022 in 90 infants aged from 1 to 4 months (mean age (± SD) 12.3 ± 5.09 weeks; 53.3% females, 46.7% males). Patients with colic, regurgitation (single symptom or combination of several symptoms), and constipation or diarrhea were randomly allocated in two parallel arms to receive either 5 drops (2 × 108 colony forming unit) of L. reuteri NCIMB 30351 (n = 60) or masked placebo (n = 30) for 25 consecutive days. Two treatment arms had equal numbers of patients with constipation and diarrhea (n = 30 each). Daily crying times and their duration, evacuations, and regurgitations were recorded in a structured diary. The levels of gut microbiota were analyzed by deep sequencing of bacterial 16S rRNA gene. Infants with colic receiving supplementary L. reuteri NCIMB 30351 for 25 days had significant reduction in the numbers of colic (change from baseline - 6.3 (7.34) vs - 3.0 (7.29) in placebo, P < 0.05) and numbers of crying cases and mean duration of crying (decrease from baseline - 144 (70.7) minutes, lower in the diarrhea subgroup than in constipation infants, compared with - 80 (58.9) in placebo, P < 0.0001), as well as regurgitation numbers (decreased by - 4.8 (2.49) with L. reuteri vs - 3 (7.74) with placebo). We also observed increased numbers of evacuations in infants with constipation (L. reuteri 2.2 (2.4) vs 0.9 (1.06) in placebo, P < 0.05). There was a remarkable reduction of evacuations in infants with diarrhea, while not statistically significant. The analysis of bacterial 16S rRNA gene in the collected samples showed that L. reuteri positively influences the proportions of prevalent species, while it negatively affects both conditionally pathogenic and commensal microbes. Additional in vitro test for formation of Clostridium colonies in the presence of the probiotic demonstrated that L. reuteri effectively inhibits the growth of pathogenic Clostridium species. No adverse events were reported in this study.   Conclusion: The uptake of L. reuteri NCIMB 30351 leads to a significant reduction in the number of regurgitations, feeding-induced constipations, and diarrhea as well as mean daily numbers of crying and crying duration in infants during the first months of life. Our results suggest that L. reuteri NCIMB 30351 represents a safe and effective treatment for colic in newborns.  Trial registration: ClinicalTrials.gov : NCT04262648. What is Known: • Infantile functional gastrointestinal disorders, such as colic, constipation, diarrhea, and gastroesophageal reflux (regurgitation), often occur in early infancy and, represent one of the causes of significant parental anxiety. • A number of studies have shown that both the composition and diversity of the intestinal microbiota play important roles in the development and function of the gastrointestinal tract. What is New: • The uptake of L. reuteri NCIMB 30351 leads to a significant reduction in the number of regurgitations, feeding-induced constipations, and diarrhea as well as mean daily numbers of crying and crying duration in infants during the first months of life. • L. reuteri positively influences the proportions of prevalent species, while it negatively affects both conditionally pathogenic and commensal microbes in gut microbiota.

Sexual activity, vaginal symptoms, maternal perineal hygiene behavior, and constipation on ano-vaginal colonization of group B streptococcus in near term pregnancy.

BACKGROUND: Maternal Group B Streptococcus (GBS) colonization is influenced by many factors but results are inconsistent. Consideration of antenatal risk factors may help inform decision making on GBS microbiological culture screening where universal screening is not standard of care. We sought to identify independent predictors of GBS colonization at 34-37 weeks gestation incorporating vaginal symptoms, perineal hygiene measures, sexual activity, and a potential novel factor, constipation. METHODS: In this prospective cross-sectional study, 573 women at 34-37 weeks gestation had an ano-vaginal swab taken and sent for selective culture for GBS. Women were asked about vaginal bleeding, discharge, irritation and candidiasis, antibiotic use during pregnancy, ano-vaginal hygiene practices such as douching and perineal cleansing after toileting, sexual intercourse related activities, and a potential novel factor for GBS carriage, constipation. Maternal basic demographics and obstetric-related characteristics were also collected. Bivariate analyses were performed to identify associates of GBS colonization. All variables with p < 0.05 found on bivariate analysis were then included into a model for multivariable binary logistic regression analysis to identify independent risk factors for GBS colonization. RESULTS: GBS colonization was found in 235/573 (41.0%) of participants. Twenty six independent variables were considered for bivariate analysis. Eight were found to have p < 0.05. Following adjusted analysis, six independent predictors of GBS colonization were identified: ethnicity, previous neonatal GBS prophylaxis, antenatal vaginal irritation, antibiotic use, recent panty liner use, and frequency of sexual intercourse. Vaginal discharge and perineal cleansing were not associated after adjustment. Recent douching and constipation were not associated on bivariate analysis. CONCLUSION: The identification of independent predictors of GBS colonization in late pregnancy may inform the woman and care provider in their shared decision making for microbiological screening at 35-38 weeks gestation in locations where universal GBS screening is not standard of care. ETHICS OVERSIGHT: This study was approved by the Medical Ethics Committee of University Malaya Medical Centre (UMMC) on August 9, 2022, reference number 2022328-11120.

Relationship Between the Frequency of Bowel Movements and Fecal Bacteroides in Japanese Women.

The intestinal microbiota is involved in many diseases, such as constipation, obesity, and inflammatory bowel disease. To determine the associations between the gut microbiome and the frequency of bowel movements, we performed cross-sectional correlation analysis at the baseline and longitudinal correlation analysis after the intervention. Forty-three women were enrolled in this study. All participants ingested soymilk-okara powder (15 g) daily for 12 weeks. They recorded the ingested okara powder amounts and their frequency of bowel movements during the entire 12 weeks of the intervention. The fecal microbiota percentages were measured at baseline and after 12 weeks of intervention. Two women who did not completely record the frequency of bowel movements were excluded. In the cross-sectional correlation analysis at the baseline, there was a significant positive correlation between the relative abundance of the Bacteroides genus in the feces and the frequency of bowel movements per week (R = 0.429, p = 0.005) and a significant negative correlation between the relative abundance of Clostridium cluster XI in the feces and the frequency of bowel movements per week (R = -0.315, p = 0.045). Moreover, in the longitudinal correlation analysis, the difference in the relative abundance of Bacteroides genus in feces between the baseline and after the intervention significantly correlated with the changes in the frequency of bowel movements per week (R = 0.492, p = 0.001). Therefore, it was suggested that there was a relationship between the gut relative abundance of the Bacteroides genus and the frequency of bowel movements.

Changes in the fecal gut microbiome of home healthcare patients with disabilities through consumption of malted rice amazake.

The aim of the present study was to investigate changes in the gut microbiome both during and after consumption of malted rice amazake (MR-Amazake), a fermented food from Japan, in-home healthcare patients with disabilities, including patients with severe motor and intellectual disabilities. We monitored 12 patients who consumed MR-Amazake for 6 wk and investigated them before and after the intervention as well as 6 wk after the end of intake to compare their physical condition, diet, type of their medication, constipation assessment scale, and analysis of their comprehensive fecal microbiome using 16S rRNA sequencing. Their constipation symptoms were significantly alleviated, and principal coordinate analysis revealed that 30% of patients showed significant changes in the gut microbiome after MR-Amazake ingestion. Furthermore, Bifidobacterium was strongly associated with these changes. These changes were observed only during MR-Amazake intake; the original gut microbiome was restored when MR-Amazake intake was discontinued. These results suggest that 6 wk is a reasonable period of time for MR-Amazake to change the human gut microbiome and that continuous consumption of MR-Amazake is required to sustain such changes.NEW & NOTEWORTHY The consumption of malted rice amazake (MR-Amazake) showed significant changes in the gut microbiome according to principal coordinate analysis in some home healthcare patients with disabilities, including those with severe motor and intellectual disabilities. After discontinuation of intake, the gut microbiome returned to its original state. This is the first pilot study to examine both the changes in the gut microbiome and their sustainability after MR-Amazake intake.

Effect of the probiotic strain, Lactiplantibacillus plantarum P9, on chronic constipation: A randomized, double-blind, placebo-controlled study.

Chronic constipation (CC) is a common gastrointestinal condition associated with intestinal inflammation, and the condition considerably impairs patients' quality of life. We conducted a large-scale 42-day randomized, double-blind, placebo-controlled trial to investigate the effect of probiotics in alleviating CC. 163 patients diagnosed with CC (following Rome IV criteria) were randomly divided into probiotic (n = 78; received Lactiplantibacillus plantarum P9 [P9]; 1 ×1011 CFU/day) and placebo (n = 85; received placebo material) groups. Ingesting P9 significantly improved the weekly mean frequency of complete spontaneous bowel movements (CSBMs) and spontaneous bowel movements (SBMs), while significantly reducing the level of worries and concerns (WO; P < 0.05). Comparing with the placebo group, P9 group was significantly enriched in potentially beneficial bacteria (Lactiplantibacillus plantarum and Ruminococcus_B gnavus), while depriving of several bacterial and phage taxa (Oscillospiraceae sp., Lachnospiraceae sp., and Herelleviridae; P < 0.05). Interesting significant correlations were also observed between some clinical parameters and subjects' gut microbiome, including: negative correlation between Oscillospiraceae sp. and SBMs; positive correlation between WO and Oscillospiraceae sp., Lachnospiraceae sp. Additionally, P9 group had significantly (P < 0.05) more predicted gut microbial bioactive potential involved in the metabolism of amino acids (L-asparagine, L-pipecolinic acid), short-/medium-chain fatty acids (valeric acid and caprylic acid). Furthermore, several metabolites (p-cresol, methylamine, trimethylamine) related to the intestinal barrier and transit decreased significantly after P9 administration (P < 0.05). In short, the constipation relief effect of P9 intervention was accompanied by desirable changes in the fecal metagenome and metabolome. Our findings support the notion of applying probiotics in managing CC.

Effects of intake of Lactococcus cremoris subsp. cremoris FC on constipation symptoms and immune system in healthy participants with mild constipation: a double-blind, placebo-controlled study.

This study evaluated the effect of Lactococcus cremoris subsp. cremoris FC (FC) on constipation symptoms and the immune system in healthy participants with mild constipation. Eighty-three participants were randomised into four groups with different doses: 50, 75, and 100 mg of freeze-dried FC (test) or corn starch (placebo). Defaecation frequency significantly increased in all test groups compared to the placebo group. Stool appearance and volume were improved considerably within the groups administered 50 mg and 75 mg of FC. The abundances of total bacteria, Bifidobacterium spp., and Lactobacillus group in the faeces showed increasing trends in the test groups. Regarding immunological parameters, the naive T cell counts in the blood were significantly higher at a dose of 75 mg of FC in the test group than in the placebo group. These results suggest that FC intake improves defaecation and some immunological parameters, especially naive T cell counts, in healthy adults.

Gut Microbial Ecosystem in Parkinson Disease: New Clinicobiological Insights from Multi-Omics.

OBJECTIVE: Gut microbiome alterations in Parkinson disease (PD) have been reported repeatedly, but their functional relevance remains unclear. Fecal metabolomics, which provide a functional readout of microbial activity, have scarcely been investigated. We investigated fecal microbiome and metabolome alterations in PD, and their clinical relevance. METHODS: Two hundred subjects (104 patients, 96 controls) underwent extensive clinical phenotyping. Stool samples were analyzed using 16S rRNA gene sequencing. Fecal metabolomics were performed using two platforms, nuclear magnetic resonance (NMR) spectroscopy and liquid chromatography-mass spectrometry. RESULTS: Fecal microbiome and metabolome composition in PD was significantly different from controls, with the largest effect size seen in NMR-based metabolome. Microbiome and NMR-based metabolome compositional differences remained significant after comprehensive confounder analyses. Differentially abundant fecal metabolite features and predicted functional changes in PD versus controls included bioactive molecules with putative neuroprotective effects (eg, short chain fatty acids [SCFAs], ubiquinones, and salicylate) and other compounds increasingly implicated in neurodegeneration (eg, ceramides, sphingosine, and trimethylamine N-oxide). In the PD group, cognitive impairment, low body mass index (BMI), frailty, constipation, and low physical activity were associated with fecal metabolome compositional differences. Notably, low SCFAs in PD were significantly associated with poorer cognition and low BMI. Lower butyrate levels correlated with worse postural instability-gait disorder scores. INTERPRETATION: Gut microbial function is altered in PD, characterized by differentially abundant metabolic features that provide important biological insights into gut-brain pathophysiology. Their clinical relevance further supports a role for microbial metabolites as potential targets for the development of new biomarkers and therapies in PD. ANN NEUROL 2021;89:546-559.

Constipation Mitigation by Rhubarb Extract in Middle-Aged Adults Is Linked to Gut Microbiome Modulation: A Double-Blind Randomized Placebo-Controlled Trial.

Gut microbiota alterations are intimately linked to chronic constipation upon aging. We investigated the role of targeted changes in the gut microbiota composition in the relief of constipation symptoms after rhubarb extract (RE) supplementation in middle-aged volunteers. Subjects (95% women, average 58 years old) were randomized to three groups treated with RE at two different doses determined by its content of rhein (supplementation of 12.5 mg and 25 mg per day) vs. placebo (maltodextrin) for 30 days. We demonstrated that daily oral supplementation of RE for 30 days was safe even at the higher dose. Stool frequency and consistency, and perceived change in transit problem, transit speed and difficulty in evacuating, investigated by validated questionnaires, were improved in both groups of RE-treated volunteers compared to placebo. Higher abundance of Lachnospiraceae (mainly Roseburia and Agathobacter) only occurred after RE treatment when present at low levels at baseline, whereas an opposite shift in short-chain fatty acid (SCFA) levels was observed in both RE-treated groups (increase) and placebo (decrease). Fecal Lachnospiraceae and SCFA were positively correlated with stool consistency. This study demonstrates that RE supplementation promotes butyrate-producing bacteria and SCFA, an effect that could contribute to relieving chronic constipation in middle-aged persons.

Efficacy of Probiotic Compounds in Relieving Constipation and Their Colonization in Gut Microbiota.

A number of studies have confirmed the relationship between constipation and gut microbiota. Additionally, many human and animal experiments have identified probiotics as effectors for the relief of constipation symptoms. In this study, probiotic compounds, including Lactobacillus acidophilus LA11-Onlly, Lacticaseibacillus rhamnosus LR22, Limosilactobacillus reuteri LE16, Lactiplantibacillus plantarum LP-Onlly, and Bifidobacterium animalis subsp. lactis BI516, were administered to mice with loperamide-induced constipation, and the impacts of these strains on constipation-related indicators and gut microbiota were evaluated. The effects of probiotic compounds on constipation relief were associated with various aspects, including gastrointestinal transit rate, number and weight of stools, serum and intestinal gastrointestinal regulatory hormones, and serum cytokines. Some of the probiotic compounds, including Limosilactobacillus reuteri, Lactiplantibacillus plantarum, and Lacticaseibacillus rhamnosus, were found to colonize the intestinal tract. Furthermore, higher dosages promoted the colonization of specific strains. This study yields a new perspective for the clinical use of probiotics to improve constipation symptoms by combining strains with different mechanisms for the alleviation of constipation.

Gut Microbiome Signatures of Risk and Prodromal Markers of Parkinson Disease.

OBJECTIVE: Alterations of the gut microbiome in Parkinson disease (PD) have been repeatedly demonstrated. However, little is known about whether such alterations precede disease onset and how they relate to risk and prodromal markers of PD. We investigated associations of these features with gut microbiome composition. METHODS: Established risk and prodromal markers of PD as well as factors related to diet/lifestyle, bowel function, and medication were studied in relation to bacterial α-/ß-diversity, enterotypes, and differential abundance in stool samples of 666 elderly TREND (Tübingen Evaluation of Risk Factors for Early Detection of Neurodegeneration) study participants. RESULTS: Among risk and prodromal markers, physical activity, occupational solvent exposure, and constipation showed associations with α-diversity. Physical activity, sex, constipation, possible rapid eye movement sleep behavior disorder (RBD), and smoking were associated with ß-diversity. Subthreshold parkinsonism and physical activity showed an interaction effect. Among other factors, age and urate-lowering medication were associated with α- and ß-diversity. Physical inactivity and constipation were highest in individuals with the Firmicutes-enriched enterotype. Constipation was lowest and subthreshold parkinsonism least frequent in individuals with the Prevotella-enriched enterotype. Differentially abundant taxa were linked to constipation, physical activity, possible RBD, smoking, and subthreshold parkinsonism. Substantia nigra hyperechogenicity, olfactory loss, depression, orthostatic hypotension, urinary/erectile dysfunction, PD family history, and the prodromal PD probability showed no significant microbiome associations. INTERPRETATION: Several risk and prodromal markers of PD are associated with gut microbiome composition. However, the impact of the gut microbiome on PD risk and potential microbiome-dependent subtypes in the prodrome of PD need further investigation based on prospective clinical and (multi)omics data in incident PD cases. ANN NEUROL 2020;88:320-331.

Gut microbiota profiles and the role of anti-CdtB and anti-vinculin antibodies in patients with functional gastrointestinal disorders (FGID).

BACKGROUND: Distinct faecal microbiota profiles are reported to be associated with various subtypes of IBS. Circulating antibodies to cytolethal distending toxin B (CdtB) and vinculin are proposed as biomarkers to identify post-infectious IBS. The aim of our study was to analyse serum levels of anti-CdtB and anti-vinculin antibodies in patients with different functional gastrointestinal disorders (FGID) and their correlation with the composition of faecal microbiome. METHODS: The study cohort comprised 65 prospectively recruited individuals: 15 with diarrhoea-type-IBS (IBS-D), 13 with constipation-type-IBS (IBS-C), 15 with functional dyspepsia (FD) and 22 healthy controls. FGID subgroups were defined according to Rome III criteria. Serum levels of anti-CdtB and anti-vinculin antibodies were measured by ELISA. Faecal microbiome composition analysis and assessment of dysbiosis were performed by GA-map® Dysbiosis Test. RESULTS: Positivity rate either for anti-CdtB or anti-vinculin antibodies was higher in the IBS-C group (76.9%) compared to IBS-D (40.0%), FD (60%) and healthy (63.6%) groups. Dysbiosis was more frequent in subjects positive for anti-CdtB antibodies and in IBS-C patients, who showed an increased amount of opportunistic/pro-inflammatory bacteria and reduced gut protective bacteria. IBS-C patients showed a high inter-individual variation of bacterial communities compared to other FGID subgroups and healthy individuals, whereas microbial profiles of patients with IBS-D and FD were overlapping with those of healthy controls. No bacteria markers showed significant differences between FGID subgroups and healthy controls. CONCLUSION: Neither anti-CdtB/anti-vinculin antibodies nor faecal microbial profiles allowed to discriminate between specific FGID subgroups. Dysbiosis was more frequent in patients presenting with anti-CdtB antibodies and in IBS-C patients.

Analysis of Gut Microbiome and Metabolite Characteristics in Patients with Slow Transit Constipation.

BACKGROUND: Slow transit constipation (STC) is a type of functional constipation in which colon transit time is extended as a result of a reduction in the high amplitude of colon contraction activity. The utility of gut microbiome and metabolite characteristics in patients with STC is rarely studied. Short-chain fatty acids (SCFAs) enhance colonic fluid and sodium absorption and thus may aggravate the symptoms of STC. However, the content and role of SCFAs in constipation patients are not clear. We speculate that gut microbiome and SCFAs in the colon of STC patients may be abnormal and linked to the underlying mechanism of STC. METHODS: This observational study is registered at ClinicalTrials.gov (NCT02984969). The high-throughput sequencing was used to analyze the diversity and composition of fecal microbial communities. Gas chromatography-mass spectrometry (GC-MS) was used to determine the properties and concentrations of the SCFAs in the two groups. RESULTS: The Shannon diversity and Simpson diversity of the gut microbiome were significantly greater in the STC group than the control group. The two groups also showed significant differences in the species composition of the gut microbiome at different classification levels. The results of GC-MS showed that the acetate concentrations in the STC group were significantly reduced compared with the control group, but the other five types of SCFAs and total SCFAs showed no significant difference between groups. ROC curve analyses revealed that the AUC of Acetate (AUC = 0.758) was higher than Propionate (AUC = 0.660). The largest AUC of gut microbiome for predicting STC was Prevotella (AUC = 0.807). Correlation analysis showed a positive correlation between the concentration of Ruminococcus and Disease history (rs = 0.519). Meanwhile, a positive correlation between the concentration of Roseburia and Acetate (rs = 0.606) or Butyrate (rs = 0.543) was found. CONCLUSION: We found significant differences between the STC and control groups in the main components of the gut microbiome, with greater diversity in the STC group and differences between the groups in species composition at different classification levels. These different microbiome and metabolite may be valuable biomarkers for STC.

Formulation of traditional Chinese medicine and its application on intestinal flora of constipated rats.

In this study, the self-extracted constipation treatment of traditional Chinese medicine extracts was applied to constipated rats. To explore the mechanism and role of the Chinese medicine for the treatment of constipation, the 16S rRNA sequencing and qRT-PCR technology were used to analyze the intestinal flora. We found that the relative abundance of Firmicutes with constipation was significantly higher accounted for 86.7%, while the gut microbiota was significantly changed after taking a certain dose of Chinese medicine, greatly increased the relative abundance of Lactobacillus accounted for 23.1%, enhanced the symbiotic relationships of Lactobacillus with other intestinal flora. The total copies of intestinal bacteria in the constipated rats decreased after taking the traditional Chinese medicine. Finally, this study results provides a theoretical basis for the treatment and understand the mechanism and effect of traditional Chinese medicine on rate constipation.

Microbiome and Its Role in Irritable Bowel Syndrome.

Irritable bowel syndrome (IBS) is an extremely common and often very debilitating chronic functional gastrointestinal disorder. Despite its prevalence, significant associated healthcare costs, and quality-of-life issues for affected individuals, our understanding of its etiology remained limited. However, it is now evident that microbial factors play key roles in IBS pathophysiology. Acute gastroenteritis following exposure to pathogens can precipitate the development of IBS, and studies have demonstrated changes in the gut microbiome in IBS patients. These changes may explain some of the symptoms of IBS, including visceral hypersensitivity, as gut microbes exert effects on the host immune system and gut barrier function, as well as the brain-gut axis. Microbial differences also appear to underlie the two main functional categories of IBS: diarrhea-predominant IBS (IBS-D) is associated with small intestinal bacterial overgrowth, which can be diagnosed by a positive hydrogen breath test, and constipation-predominant IBS (IBS-C) is associated with increased levels of methanogenic archaea, which can be diagnosed by a positive methane breath test. Mechanistically, the pathogens that cause gastroenteritis and trigger subsequent IBS development produce a common toxin, cytolethal distending toxin B (CdtB), and antibodies raised against CdtB cross-react with the cytoskeletal protein vinculin and impair gut motility, facilitating bacterial overgrowth. In contrast, methane gas slows intestinal contractility, which may facilitate the development of constipation. While antibiotics and dietary manipulations have been used to relieve IBS symptoms, with varying success, elucidating the specific mechanisms by which gut microbes exert their effects on the host may allow the development of targeted treatments that may successfully treat the underlying causes of IBS.

What's in the pipeline for lower functional gastrointestinal disorders in the next 5 years?

The overall objectives of this review are to summarize actionable biomarkers for organic etiology of lower functional gastrointestinal disorders (FGIDs) that lead to individualized treatment for their FGIDs and to assess the pipeline for novel approaches to the management of constipation, diarrhea, and chronic abdominal pain in lower FGIDs. The new approaches to therapy include ion exchangers/transporters for functional constipation (sodium-glucose cotransporter 1, Na+/H+ exchanger 3, and solute carrier family 26 member 3 inhibitors), bile acid modulators for constipation such as ileal bile acid transporter inhibitors and fibroblast growth factor 19 analog for functional constipation, and bile acid sequestrants or farnesoid X receptor agonists for functional diarrhea. Treatment for chronic abdominal pain remains an unmet need in patients with lower FGIDs, and promising novel approaches include delayed-release linaclotide, nonclassical opioid visceral analgesics, and selective cannabinoid receptor agonists. The role of probiotics, fecal microbial transplantation, and possible future microbiome therapies is discussed.

Obesity, Motility, Diet, and Intestinal Microbiota-Connecting the Dots.

PURPOSE OF REVIEW: The goal of the present review is to explore the relationship between dietary changes and alterations in gut microbiota that contribute to disorders of gut motility and obesity. RECENT FINDINGS: We review the microbiota changes that are seen in obesity, diarrhea, and constipation and look at potential mechanisms of how dysbiosis can predispose to these. We find that microbial metabolites, particularly short chain fatty acids, can lead to signaling changes in the host enterocytes. Microbial alteration leading to both motility disorders and obesity may be mediated by the release of hormones including glucagon-like peptides 1 and 2 (GLP-1, GLP-2) and polypeptide YY (PYY). These pathways provide avenues for microbiota-targeted interventions that can treat both disorders of motility and obesity. In summary, multiple mechanisms contribute to the interplay between the microbial dysbiosis, obesity, and dysmotility.

The Effect of Psyllium Husk on Intestinal Microbiota in Constipated Patients and Healthy Controls.

Psyllium is a widely used treatment for constipation. It traps water in the intestine increasing stool water, easing defaecation and altering the colonic environment. We aimed to assess the impact of psyllium on faecal microbiota, whose key role in gut physiology is being increasingly recognised. We performed two randomised, placebo-controlled, double-blinded trials comparing 7 days of psyllium with a placebo (maltodextrin) in 8 healthy volunteers and 16 constipated patients respectively. We measured the patients' gastrointestnal (GI) transit, faecal water content, short-chain fatty acid (SCFA) and the stool microbiota composition. While psyllium supplement had a small but significant effect on the microbial composition of healthy adults (increasing Veillonella and decreasing Subdoligranulum), in constipated subjects there were greater effects on the microbial composition (increased Lachnospira, Faecalibacterium, Phascolarctobacterium, Veillonella and Sutterella and decreased uncultured Coriobacteria and Christensenella) and alterations in the levels of acetate and propionate. We found several taxa to be associated with altered GI transit, SCFAs and faecal water content in these patients. Significant increases in three genera known to produce butyrate, Lachnospira, Roseburia and Faecalibacterium, correlated with increased faecal water. In summary, psyllium supplementation increased stool water and this was associated with significant changes in microbiota, most marked in constipated patients.