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.

Effects of Heat-Treated Lactobacillus helveticus CP790-Fermented Milk on Gastrointestinal Health in Healthy Adults: A Randomized Double-Blind Placebo-Controlled Trial.

Probiotic-fermented milk is commonly used to maintain intestinal health. However, the effects of heat-treated fermented milk, which does not contain live microorganisms, on intestinal function are not yet fully understood. This study aimed to investigate whether heat-treated Lactobacillus helveticus CP790-fermented milk affects fecal microbiota and gut health as a "postbiotic". A randomized, double-blind, placebo-controlled trial was conducted in healthy Japanese individuals aged 20-59 years with a tendency toward constipation. Participants consumed 100 mL of either the test beverage (n = 60) or placebo beverage (n = 60) for four weeks. The test beverages were prepared with heat-treated CP790-fermented milk, while the placebo beverages were prepared with nonfermented milk flavored with lactic acid. Fecal samples were analyzed using 16S rRNA gene sequencing. Constipation symptoms were assessed using defecation logs and the Patient Assessment of Constipation Symptoms (PAC-SYM) questionnaire. Mood state was also assessed using the Profile of Mood States 2 (POMS2) questionnaire to explore its potential as a "psychobiotic". Desulfobacterota were significantly decreased by CP790-fermented milk intake. PICRUSt2 analysis predicted a decrease in the proportion of genes involved in the sulfate reduction pathway following the consumption of CP790-fermented milk. The CP790-fermented milk intervention significantly improved stool consistency and straining during defecation. These improvements were correlated with a decrease in Desulfobacterota. After the intervention, overall mood, expressed as total mood disturbance, and depression-dejection were significantly better in the CP790 group than in the placebo group. These results suggest that the intake of CP790-fermented milk could be effective in modulating gut microbiota and improving constipation symptoms and mood states.

Probiotics combination effectively improves constipation in pregnancy by modifying the gut microbiota composition.

Constipation during pregnancy can induce serious complications, including miscarriage and preterm labour, while the evidence of probiotics in improving constipation during pregnancy was little. In this study, 29 healthy pregnant women and 65 constipated pregnant women were enrolled to assess the effectiveness of probiotics on constipation during pregnancy. Our results showed that the probiotics were effective in improving the Constipation Severity Scale (CSS) and Bristol Stool Scale (BSS) scores, including increasing defecation frequency, decreasing defecation time, and improving fecal characteristics. 16S rRNA sequencing revealed that the probiotics effectively restored the diversity of intestinal microbiota. At the phylum level, Firmicutes (13.27% vs 57.20%) and Actinobacteria (3.77% vs 12.80%) were increased, while Bacteroidetes (77.82% vs 20.24%) was decreased. At the level of the genus, Faecalibacterium (2.03% vs 10.33%), Bifidobacterium (1.21% vs 8.56%), and Phascolarctobacterium (0.05% vs 2.88%), the beneficial bacteria were increased, while the Bacteroides (29.23% vs 12.28%) and Prevotella (24.32% vs 4.92%) were decreased. In conclusion, these results indicated that probiotics can effectively relieve the constipation symptoms by improving the diversity of intestinal microbiota, regulating the disturbance of microflorae, and restoring the balance of microflorae to exert a stronger moderating effect than diet and lifestyle modification. Our results provided clinical data and a theoretical basis for the exploitation of probiotics in treating constipation during pregnancy. Chinese Clinical Trial Registry: ChiCTR2100052069.

Aberrant bowel movement frequencies coincide with increased microbe-derived blood metabolites associated with reduced organ function.

Bowel movement frequency (BMF) directly impacts the gut microbiota and is linked to diseases like chronic kidney disease or dementia. In particular, prior work has shown that constipation is associated with an ecosystem-wide switch from fiber fermentation and short-chain fatty acid production to more detrimental protein fermentation and toxin production. Here, we analyze multi-omic data from generally healthy adults to see how BMF affects their molecular phenotypes, in a pre-disease context. Results show differential abundances of gut microbial genera, blood metabolites, and variation in lifestyle factors across BMF categories. These differences relate to inflammation, heart health, liver function, and kidney function. Causal mediation analysis indicates that the association between lower BMF and reduced kidney function is partially mediated by the microbially derived toxin 3-indoxyl sulfate (3-IS). This result, in a generally healthy context, suggests that the accumulation of microbiota-derived toxins associated with abnormal BMF precede organ damage and may be drivers of chronic, aging-related diseases.

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.

The relationship between small intestinal bacterial overgrowth and constipation in children - a comprehensive review.

Small intestinal bacterial overgrowth (SIBO) is characterized by an increase in the bacterial population of the small intestine due to an imbalance between the amount of bacteria and the intestinal barrier. Pediatric SIBO presents with a wide spectrum of symptoms, ranging from mild gastrointestinal complaints to malabsorption or malnutrition. Breath tests are commonly used as noninvasive diagnostic tools for SIBO, but a standardized methodology is currently unavailable. Intestinal flora produces methane which slows intestinal transit and increases the contractile activity of small intestine. Emerging literature suggests a correlation between overgrowth of methanogenic bacteria in the intestines and constipation. Treatment of SIBO involves administration of antibacterial therapy in addition to management of underlying conditions and optimal dietary adjustments. However, research on antibiotic treatment for pediatric patients with constipation and SIBO is limited and has yielded conflicting results. In the current review, we summarize the state-of-the-art of the field and discuss previous treatment attempts and currently used regimens for SIBO patients with constipation, with a focus on pediatric populations.

Microbial imbalance in Chinese children with diarrhea or constipation.

Diarrhea and constipation are common health concerns in children. Numerous studies have identified strong association between gut microbiota and digestive-related diseases. But little is known about the gut microbiota that simultaneously affects both diarrhea and constipation or their potential regulatory mechanisms. Stool samples from 618 children (66 diarrhea, 138 constipation, 414 healthy controls) aged 0-3 years were collected to investigate gut microbiota changes using 16S rRNA sequencing. Compared with healthy, children with diarrhea exhibited a significant decrease in microbial diversity, while those with constipation showed a marked increase (p < 0.05). Significantly, our results firstly Ruminococcus increased in constipation (p = 0.03) and decreased in diarrhea (p < 0.01) compared to healthy controls. Pathway analysis revealed that Ruminococcus highly involved in the regulation of five common pathways (membrane transport, nervous system, energy metabolism, signal transduction and endocrine system pathways) between diarrhea and constipation, suggesting a potential shared regulatory mechanism. Our finding firstly reveals one core microorganisms that may affect the steady balance of the gut in children with diarrhea or constipation, providing an important reference for potential diagnosis and treatment of constipation and diarrhea.

Clinical effects of chemical drugs, fecal microbiota transplantation, probiotics, dietary fiber, and acupuncture in the treatment of chronic functional constipation: a systematic review and network meta-analysis.

Currently, there are increasingly diverse treatment modalities for chronic functional constipation (CFC). This study aims to compare the relative efficacy and safety of chemical drugs, fecal microbiota transplantation (FMT), probiotics, dietary fiber, and acupuncture in the treatment of patients with CFC. We searched relevant randomized controlled trials (RCTs) published in five databases up to November 2023. Network meta-analysis (NMA) was carried out using R Studio 4.2.1. Cumulative ranking probability plots, assessed through the surface under the cumulative ranking (SUCRA), were employed to rank the included drugs for various outcome measures. We included a total of 45 RCT studies with 17 118 patients with CFC. From the SUCRA values and NMA results FMT showed the best utility in terms of clinical efficacy, Bristol stool form scale scores, patient assessment of constipation quality of life scores, and the treatment modality with the lowest ranked incidence of adverse effects was electroacupuncture. Subgroup analysis of the chemotherapy group showed that sodium A subgroup analysis of the chemical group showed that sodium picosulfate 10 mg had the highest clinical efficacy. FMT is more promising in the treatment of CFC and may be more effective in combination with the relatively safe treatment of acupuncture.

Colorectal Disease and the Gut Microbiome: What a Surgeon Needs to Know.

The gut microbiome is defined as the microorganisms that reside within the gastrointestinal tract and produce a variety of metabolites that impact human health. These microbes play an intricate role in human health, and an imbalance in the gut microbiome, termed gut dysbiosis, has been implicated in the development of varying diseases. The purpose of this review is to highlight what is known about the microbiome and its impact on colorectal cancer, inflammatory bowel disease, constipation, Clostridioides difficile infection, the impact of bowel prep, and anastomotic leaks.

Different microbial ecological agents change the composition of intestinal microbiota and the levels of SCFAs in mice to alleviate loperamide-induced constipation.

Probiotics exert beneficial effects by regulating the intestinal microbiota, metabolism, immune function and other ways of their host. Patients with constipation, a common gastrointestinal disorder, experience disturbances in their intestinal microbiota. In the present study, we investigated the effectiveness of two microbial ecological agents (postbiotic extract PE0401 and a combination of postbiotic extract PE0401 and Lacticaseibacillus paracasei CCFM 2711) in regulating the makeup of the intestinal microbiota and alleviating loperamide hydrochloride-induced constipation in mice. We also preliminarily explored the mechanism underlying their effects. Both microbial ecological agents increased the abundance of the beneficial bacteria Lactobacilli and Bifidobacterium after administration and were able to relieve constipation. However, the degree of improvement in constipation symptoms varied depending on the makeup of the supplement. The postbiotic extract PE0401 increased peristalsis time and improved faecal properties throughout the intestinal tract of the host. PE0401 relieved constipation, possibly by modulating the levels of the constipation-related gastrointestinal regulatory transmitters mouse motilin, mouse vasoactive intestinal peptide, and 5-hydoxytryptamine in the intestinal tract of the host and by increasing the levels of the short-chain fatty acids (SCFAs) acetic acid, propionic acid, and isovaleric acid. It also increased the relative abundance of Lactobacillus and Bifidobacterium and reduced that of Faecalibaculum, Mucispirillum, Staphylococcus, and Lachnoclostridium, which are among the beneficial microbiota in the host intestine. Furthermore, PE0401 decreased the levels of constipation-induced host inflammatory factors. Therefore, the two microbial ecological agents can regulate the intestinal microbiota of constipation mice, and PE0401 has a stronger ability to relieve constipation.

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.

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.

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.

Gastrointestinal Dysmotility Predisposes to Colitis through Regulation of Gut Microbial Composition and Linoleic Acid Metabolism.

Disrupted gastrointestinal (GI) motility is highly prevalent in patients with inflammatory bowel disease (IBD), but its potential causative role remains unknown. Herein, the role and the mechanism of impaired GI motility in colitis pathogenesis are investigated. Increased colonic mucosal inflammation is found in patients with chronic constipation (CC). Mice with GI dysmotility induced by genetic mutation or chemical insult exhibit increased susceptibility to colitis, dependent on the gut microbiota. GI dysmotility markedly decreases the abundance of Lactobacillus animlalis and increases the abundance of Akkermansia muciniphila. The reduction in L. animlalis, leads to the accumulation of linoleic acid due to compromised conversion to conjugated linoleic acid. The accumulation of linoleic acid inhibits Treg cell differentiation and increases colitis susceptibility via inducing macrophage infiltration and proinflammatory cytokine expression in macrophage. Lactobacillus and A. muciniphila abnormalities are also observed in CC and IBD patients, and mice receiving fecal microbiota from CC patients displayed an increased susceptibility to colitis. These findings suggest that GI dysmotility predisposes host to colitis development by modulating the composition of microbiota and facilitating linoleic acid accumulation. Targeted modulation of microbiota and linoleic acid metabolism may be promising to protect patients with motility disorder from intestinal inflammation.

Adjunctive efficacy of Bifidobacterium animalis subsp. lactis XLTG11 for functional constipation in children.

Functional constipation (FC) can seriously affect the physical and mental health of children. The goal of this study is to assess the efficacy and safety of Bifidobacterium animalis subsp. lactis XLTG11 in treating FC in children through a randomized, double-blinded, placebo-controlled approach. Eligible children were randomized into either the intervention group (IG, n = 65, receiving conventional treatment with probiotics) or the control group (CG, n = 66, receiving conventional treatment without probiotics). The primary outcome measure was fecal frequency. Fecal gut microbiota analysis and PICRUSt (Phylogenetic Investigation of Communities by Reconstruction of Unobserved States) were used to predict gene family abundances based on 16S information. Over the course of treatment, the weekly frequency of feces within each group increased significantly (F = 41.97, p < 0.001). The frequency of feces (times/week (t/w)) in the IG was significantly higher than that in the CG (3.69 ± 2.62 t/w vs.3.18 ± 1.43 t/w, 4.03 ± 2.54 t/w vs. 2.89 ± 1.39 t/w and 3.74 ± 2.36 t/w vs. 2.94 ± 1.18 t/w and 3.45 ± 1.98 vs. 3.17 ± 1.41 t/w for the 1st, 2nd, 3rd, and 4th week after intervention, respectively) (F = 7.60, p = 0.0067). After the intervention, dominate species shifted to Bifidobacterium longum, Bifidobacterium breve, and Escherichia coli in the IG. Additionally, genes related to short-chain fatty acid (SCF) metabolism were upregulated, while methane metabolism was downregulated. Administration of XLTG11 at a dose of 1 × 1010 CFU/day to children increased fecal frequency, induced beneficial changes in gut microbiota, and regulated SCFs and methane metabolism-related genes.

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.

A key genetic factor governing arabinan utilization in the gut microbiome alleviates constipation.

Impaired gastrointestinal motility is associated with gut dysbiosis. Probiotics, such as Bifidobacteria, can improve this bowel disorder; however, efficacy is strain-dependent. We determine that a genetic factor, the abfA cluster governing arabinan utilization, in Bifidobacterium longum impacts treatment efficacy against functional constipation (FC). In mice with FC, B. longum, but not an abfA mutant, improved gastrointestinal transit time, an affect that was dependent upon dietary arabinan. abfA genes were identified in other commensal bacteria, whose effects in ameliorating murine FC were similarly abfA-dependent. In a double-blind, randomized, placebo-controlled clinical trial, supplementation with abfA-cluster-carrying B. longum, but not an abfA-deficient strain, enriched arabinan-utilization residents, increased beneficial metabolites, and improved FC symptoms. Across human cohorts, abfA-cluster abundance can predict FC, and transplantation of abfA cluster-enriched human microbiota to FC-induced germ-free mice improved gut motility. Collectively, these findings demonstrate a role for microbial abfA cluster in ameliorating FC, establishing principles for genomics-directed probiotic therapies.

The Different Ways Multi-Strain Probiotics with Different Ratios of Bifidobacterium and Lactobacillus Relieve Constipation Induced by Loperamide in Mice.

Constipation is currently one of the most common gastrointestinal disorders, and its causes are diverse. Multi-strain probiotics are often considered a more effective treatment than single-strain probiotics. In this study, a constipation model was constructed using loperamide hydrochloride to evaluate the ability of a multi-strain probiotic combination of four different ratios of Bifidobacterium and Lactobacillus to regulate intestinal flora, relieve constipation, and explore the initial mechanism in mice. After four weeks of probiotic intervention, BM1, BM2, and PB2 effectively relieved constipation; however, the pathways involved were different. The Bifidobacteria-dominated formulations BM1 and BM2 mainly changed the composition and structure of the intestinal flora and significantly decreased the relative abundance of Tyzzerella, Enterorhabdus, Faecalibaculum, Gordonibacter, and Mucispirillum in stool; increased the relative abundance of Parabacteroides and the content of short-chain fatty acids (SCFAs) in stool; restored motilin (MTL) and vasoactive intestinal peptide (VIP) levels; and downregulated interleukin 6 (IL-6) and IL-8 levels in serum. This repaired the inflammatory response caused by constipation. Finally, it promoted peristalsis of the gastrointestinal tract, increasing stool water content, and relieving constipation. While Lactobacillus-dominated formula PB2 mainly restored the levels of serum neurotransmitters (MTL, SP (substance P), VIP and PYY (Peptide YY)) and inflammatory factors (IL-1, IL-6 and IL-8), it significantly decreased the relative abundance of Tyzzerella, Enterorhabdus, Faecalibaculum, Gordonibacter and Mucispirillum in stool; it then increased acetic acid content, thereby reducing the level of inflammation and changing stool properties and gastrointestinal motility.

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.

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.