Probiotic Properties of Bifidobacterium longum KABP042 and Pediococcus pentosaceus KABP041 Show Potential to Counteract Functional Gastrointestinal Disorders in an Observational Pilot Trial in Infants

Functional gastrointestinal disorders (FGIDs) are a common concern during the first year of life. Recognized as gut-brain axis disorders by Rome IV criteria, FGIDs etiology is linked to altered gut-brain interaction, intestinal physiology, and microbiota. In this regard, probiotics have emerged as a promising therapy for infant FGIDs. In this study, we have investigated the probiotic potential of the strains Bifidobacterium longum KABP042 and Pediococcus pentosaceus KABP041—isolated from healthy children’s feces—in the treatment of FGIDs. To this scope, genome sequences of both strains were obtained and subjected to in silico analyses. No virulence factors were detected for any strain and only the non-transferable erm(49) gene, which confers resistance to erythromycin and clindamycin, was identified in the genome of B. longum KABP042. Safety of both strains was confirmed by acute oral toxicity in rats. In vitro characterization revealed that the strains tolerate gastric and bile challenges and display a great adhesion capacity to human intestinal cells. The two strains mediate adhesion by different mechanisms and, when combined, synergically induce the expression of Caco-2 tight junction proteins. Moreover, growth inhibition experiments demonstrated the ability of the two strains alone and in combination to antagonize diverse Gram-negative and Gram-positive bacterial pathogens during sessile and planktonic growth. Pathogens’ inhibition was mostly mediated by the production of organic acids, but neutralization experiments strongly suggested the presence of additional antimicrobial compounds in probiotic culture supernatants such as the bacteriocin Lantibiotic B, whose gene was detected in the genome of B. longum KABP042. Finally, an exploratory, observational, pilot study involving 36 infants diagnosed with at least one FGID (infant colic and/or functional constipation) showed the probiotic formula was well tolerated and FGID severity was significantly reduced after 14 days of treatment with the 2 strains. Overall, this work provides evidence of the probiotic and synergic properties of strains B. longum KABP042 and P. pentosaceus KABP041, and of their potential to treat pediatric FGIDs.Clinical Trial Registration: [www.ClinicalTrials.gov], [identifier NCT04944628].

The Effect of An Aloe-Based Polyherbal Formulation in Adults with Functional Constipation: A Randomized, Double-Blind, Placebo-Controlled, Six-Months Clinical Follow-up Trial

The most common functional gastrointestinal problem in the world is functional constipation. "Ayarij-e-Faiqra (AF)" is a polyherbal formula that has been recommended by Persian Medicine as an efficent purgative agent . The purpose of this study was to evaluate the effect of AF on functional constipation using a double-blind, placebo-controlled clinical trial. According to the Rome III classification, 79 adults with functional constipation were included in this trial. The diagnostic criteria were according to the Rome III classification. Patients with constipation symptoms who referred to the traditional medicine clinic of Shahid Beheshti University of Medical Sciences from April 2014 to September 2016 were randomly allocated to the AF and placebo groups. The AF and placebo groups received AF and placebo for three months, respectively and followed up for another three months. During the study, the treatment efficacy was assessed by a questionnaire. AF treatment significantly decreased most of the symptoms by 84% at the end of the first month (p < 0.05) and by 90% at the end of the third month in comparison to placbo group (p < 0.001). However, three months after the end of the intervention, the frequency of constipation symptoms in both groups was not statistically significant. Based on the satisfaction questionnaire, the treatment satisfaction score during the intervention was increased to 9 in the AF group, but no significant difference was found between the two groups three months after the intervention (p > 0.005). Although AF could be beneficial for treating functional constipation without significant side effects, changing patients’ lifestyles has great importance in this process.

Transcriptomic Signatures Associated With Gray Matter Volume Changes in Patients With Functional Constipation

Functional constipation, which belongs to the functional gastrointestinal disorder (FGID), is a common disease and significantly impacts daily life. FGID patients have been progressively proven with functional and structural alterations in various brain regions, but whether and how functional constipation affects the brain gray matter volume (GMV) remains unclear; besides, which genes are associated with the GMV changes in functional constipation is largely unknown. On account of the structural MRI image from the 30 functional constipation patients and 30 healthy controls (HCs), GMV analysis showed that functional constipation patients had significantly decreased GMV in the right orbital prefrontal cortex (OFC), left precentral gyrus (PreG), and bilateral thalamus (THA). Correlation analysis showed that the self-rating depressive scale, patient assessment of constipation quality of life (PAC-QOL), and Wexner constipation scores were negatively correlated with GMV of the OFC and negative correlations between PAC-QOL score and GMV of the bilateral THA. Based on the Allen Human Brain Atlas, a cross-sample spatial correlation was conducted and found that 18 genes’ expression values showed robust correlations with GMV changes in functional constipation patients. These outcomes highlight our recognition of the transcriptional features related to GMV changes in functional constipation and could be regarded as candidates to detect biological mechanisms of abnormality in functional constipation patients.

Clinical and metabolic effects of metaprebiotic therapy for some functional bowel diseases

Aim of investigation: to assess the effectiveness and tolerance of dietary supplements (BAA) STIM and STIM LaxMaterials and methods: The analysis of the treatment of 73 patients who were divided into 2 groups. Group 1-32 patients with functional constipation (8 men and 24 women; mean age — 45.7 ± 12.4 years), Group 2-41 patients with functional diarrhea (19 men and 22 women; mean age — 41.0 ± 15,8 years). The study of clinical symptoms was carried out according to the data of an individual diary, using specialized questionnaires with a scoring of symptoms before and after the course of treatment, before and after treatment, the result of the carbolene test, the content of short-chain fatty acids in the feces was assessed. Tolerability was assessed by recording side effects and adverse events.Monotherapy was carried out with STIM LAX for patients with functional constipation at a dose of 1 tablet 3 times a day for 30 days. STIM for patients with functional diarrhea was prescribed in a dose of 2 tablets 3 times a day for 30 days.Results of the study: The results of the study showed that FC therapy with StimLax effectively reduces the frequency and intensity of symptoms such as difficulty / pain, discomfort during defecation, feeling of incomplete emptying, abdominal pain, time spent in the toilet and the number of failed bowel movements. We observed the normalization of transit time according to the carbolene test and an increase in stool frequency up to 5 times a week.Treatment of patients with FD with Stim led to a significant decrease in the intensity of abdominal pain, rumbling, flatulence, stool frequency, an increase in the time of the carbolene test and the normalization of its consistency.Adverse events were observed in 8 (10.9%) patients (4 patients with FD and 4 patients with FD). On the 3-5th day of treatment, there was an increase in flatulence, rumbling in the abdomen. A temporary decrease in the dose of the drug to 1-2 tablets per day removed these phenomena and the symptoms that appeared were resolved within 1-3 days. After that, the dose of the drug was gradually increased to the initial (effective), which the patients tolerated normally.Conclusions: The results of this study indicate high clinical efficacy and good tolerability of treatment with drugs StimLax and Stim in patients with FC and FD. In some cases, it is necessary to titrate the dose of the drug (downward), but this is not accompanied by a decrease in the effectiveness of therapy. The use of these drugs with metaprebiotic properties helps to modify the microbiota of patients with functional bowel diseases. With constipation, the number and activity of both lactic acid flora and microorganisms that produce butyric acid are stimulated; in addition, calcium lactate is an additional source of butyric acid due to metabolism. With diarrhea, along with the stimulation of the number and activity of the lactic acid flora, there is an improvement in the utilization of butyrate by intestinal cells.

Evaluation of diagnostic factors used to refer children with constipation for rectal biopsies

Purpose Children with constipation and suspected Hirschsprung’s disease are referred for rectal biopsy. Since this is an invasive procedure, appropriate indications should be applied to minimize the number of “unnecessary” biopsies. Methods We reviewed all constipated children who underwent a rectal biopsy to diagnose a possible Hirschsprung’s disease at a tertiary referral hospital over a 6-year period (2013–2018). We registered clinical and demographic factors in these children and conducted correlation and multivariate regression analysis to evaluate the relation between these factors and a diagnosis of Hirschsprung’s disease. Results We identified 225 children, aged 0–17 years. In total, Hirschsprung’s disease was diagnosed in only 49/225 (22%). Among the 49 children with Hirschsprung’s disease, 29 (59%) were diagnosed in the neonatal period. Among girls, HD was confirmed in only 10/101 (10%) children, and only 1 of these 10 girls was older than 6 months at the time of the biopsy. The following factors correlated significantly with Hirschsprung’s disease diagnosis in children older than 1 month: “male sex”, “failure to thrive”, “gross abdominal distention plus vomiting” and “fulfils the Rome 4 criteria for functional constipation”. Conclusion In children referred for rectal biopsy, the factors most indicative of Hirschsprung’s disease were “male sex”, “failure to thrive”, “gross abdominal distention plus vomiting” and “fulfils the Rome 4 criteria for functional constipation”. Notably, the prevalence of Hirschsprung’s disease decreased with the increasing age of the children. Girls referred for a biopsy rarely had Hirschsprung’s disease, especially those older than 1 month.

Brain Structural Changes in Regions Within the Salience Network in Patients with Functional Constipation

Functional constipation (FCon) is one of the common functional gastrointestinal disorders (FGID). Previous studies reported alterations in cortical morphometry as well as changes in white matter (WM) fiber tracts and thalamo-limbic/parietal structural connectivity (SC). However, whether patients with FCon are implicated in changes in gray matter (GM) volume and associated SC remains unclear. Voxel-based morphometry (VBM) was first employed to examine differences in GM volume between 48 patients with FCon and 52 healthy controls (HC). Diffusion tensor imaging (DTI) with probabilistic tractography analysis was then employed to explore alterations in SC of these regions. Compared with the HC, patients with FCon showed decreased GM volumes in the right middle frontal gyrus (MFG_R), left insula (INS_L), and anterior cingulate cortex (ACC, PFWE < 0.05) which had a negative correlation with abdominal symptoms and difficulty of defecation respectively. Seed-based SC showed patients with FCon had decreased fractional anisotropy (FA) of bilateral INS-ACC, bilateral ACC-MFG, bilateral INS-MFG, increased axial diffusivity (AD) of bilateral ACC-MFG, and decreased radial diffusivity (RD) of bilateral INS-ACC, bilateral ACC-MFG tracts. FA of the right INS-ACC tract had a negative correlation with difficulty of defecation and AD of the ACC-left MFG tract had a negative correlation with stool symptoms. These findings reflect patients with FCon are implicated in changes in GM volumes and corresponding SC in brain regions within the salience network.