This study explores the impact of defecation frequency on the gut microbiome structure by analyzing fecal samples from individuals categorized by defecation frequency: infrequent (1-3 times/week, n = 4), mid-frequent (4-6 times/week, n = 7), and frequent (daily, n = 9). Utilizing 16S rRNA gene-based sequencing and LC-MS/MS metabolome profiling, significant differences in microbial diversity and community structures among the groups were observed. The infrequent group showed higher microbial diversity, with community structures significantly varying with defecation frequency, a pattern consistent across all sampling time points. The Ruminococcus genus was predominant in the infrequent group, but decreased with more frequent defecation, while the Bacteroides genus was more common in the frequent group, decreasing as defecation frequency lessened. The infrequent group demonstrated enriched biosynthesis genes for aromatic amino acids and branched-chain amino acids (BCAAs), in contrast to the frequent group, which had a higher prevalence of genes for BCAA catabolism. Metabolome analysis revealed higher levels of metabolites derived from aromatic amino acids and BCAA metabolism in the infrequent group, and lower levels of BCAA-derived metabolites in the frequent group, consistent with their predicted metagenomic functions. These findings underscore the importance of considering stool consistency/frequency in understanding the factors influencing the gut microbiome.

Recent advances in microbiome research have led to the further development of microbial interventions, such as probiotics and prebiotics, which are potential treatments for constipation. However, the effects of probiotics vary from person to person; therefore, the effectiveness of probiotics needs to be verified for each individual. Individuals showing significant effects of the target probiotic are called responders. A statistical model for the evaluation of responders was proposed in a previous study. However, the previous model does not consider the lag between intake and effect periods of the probiotic. It is expected that the lag exists when probiotics are administered and when they are effective. In this study, we propose a Bayesian statistical model to estimate the probability that a subject is a responder, by considering the lag between intake and effect periods. In synthetic dataset experiments, the proposed model was found to outperform the base model, which did not factor in the lag. Further, we found that the proposed model could distinguish responders showing large uncertainty in terms of the lag between intake and effect periods.

Cognitive decline and constipation are common complications in the elderly. Probiotics are potential therapeutic agents to ameliorate cognitive impairment through gut-brain axis. Several clinical studies have investigated the beneficial effects of probiotics on cognitive impairment and constipation in elderly. However, a quantitative meta-analysis is required to evaluate the efficacy of probiotics on cognitive function and constipation. Thirteen clinical studies were included in this meta-analysis. We examined the risk of bias assessment and heterogeneity of eight studies for cognition and five studies for constipation, followed by group and subgroup meta-analyses using a random-effects model to evaluate the potential of probiotic supplements on cognition function and constipation in aged people. The results of the pooled meta-analysis revealed that probiotic supplementation did not improve the cognitive rating scale assessment for all studies (estimate = 0.13; 95%CI [-0.18, 0.43]; p = 0.41; I2 = 83.51%). However, subgroup analysis of single strain supplementation showed improved cognitive function in elderly people (estimate = 0.35; 95%CI [0.02, 0.69]; p = 0.039; I2 = 19.19%) compared to multiple strains. Probiotics also enhanced defecation frequency in constipated patients (estimate = 0.27; 95%CI [0.05, 0.5]; p = 0.019; I2 = 67.37%). Furthermore, probiotic supplementation resulted in higher fecal Lactobacillus counts than placebo (estimate = 0.37; 95%CI [0.05, 0.69]; p = 0.026; I2 = 21.3%). Subgroup analysis indicated that a probiotic intervention period of ≥4 weeks was more effective (estimate = 0.35; 95%CI [0.01, 0.68]; p = 0.044; I2 = 0%) in reducing constipation symptoms than a short intervention duration. Based on these results, probiotic supplementation could be a potential intervention to reduce constipation symptoms in the elderly population. The heterogeneity between studies is high, and limited trials are available to evaluate the cognitive function of aged individuals using probiotics. Therefore, further studies are required to determine the effect of probiotics on cognition.

Necrotizing enterocolitis (NEC) is associated with significant morbidity and mortality in preterm infants. Early recognition and treatment of NEC are critical to improving outcomes. Enteric nervous system (ENS) immaturity has been proposed as a key factor in NEC pathophysiology. Gastrointestinal dysmotility is associated with ENS immaturity and may serve as a predictive factor for the development of NEC. In this case-control study, preterm infants (gestational age (GA) < 30 weeks) were included in two level-IV neonatal intensive care units. Infants with NEC in the first month of life were 1:3 matched to controls based on GA (± 3 days). Odds ratios for NEC development were analyzed by logistic regression for time to first passage of meconium (TFPM), duration of meconial stool, and mean daily defecation frequency over the 72 h preceding clinical NEC onset (DF < T0). A total of 39 NEC cases and 117 matched controls (median GA 27 + 4 weeks) were included. Median TFPM was comparable in cases and controls (36 h [IQR 13-65] vs. 30 h [IQR 9-66], p = 0.83). In 21% of both cases and controls, TFPM was ≥ 72 h (p = 0.87). Duration of meconial stool and DF < T0 were comparable in the NEC and control group (median 4 and 3, resp. in both groups). Odds of NEC were not significantly associated with TFPM, duration of meconial stools, and DF < T0 (adjusted odds ratio [95% confidence interval]: 1.00 [0.99-1.03], 1.16 [0.86-1.55] and 0.97 [0.72-1.31], resp.).
CONCLUSIONS: In this cohort, no association was found between TFPM, duration of meconium stool, and DF < T0 and the development of NEC.
BACKGROUND: • Necrotizing enterocolitis (NEC) is a life-threatening acute intestinal inflammatory disease of the young preterm infant. Early clinical risk factors for NEC have been investigated in order to facilitate early diagnosis and treatment. • Signs of disrupted gastrointestinal mobility, such as gastric retention and paralytic ileus, have been established to support the diagnosis of NEC. Nevertheless, defecation patterns have insufficiently been studied in relation to the disease.
BACKGROUND: • Defecation patterns in the three days preceding NEC did not differ from gestational age-matched controls of corresponding postnatal age. Additionally, the first passage of meconium and the duration of meconium passage were comparable between cases and controls. Currently, defecation patterns are not useful as early warning signs for NEC. It remains to be elucidated whether these parameters are different based on the location of intestinal necrosis.

Eluxadoline (ELD), a recently approved drug, exhibits potential therapeutic effects in the management and treatment of IBS-D. However, its applications have been limited due to poor aqueous solubility, leading to a low dissolution rate and oral bioavailability. The current study\'s goals are to prepare ELD-loaded eudragit (EG) nanoparticles (ENPs) and to investigate the anti-diarrheal activity on rats. The prepared ELD-loaded EG-NPs (ENP1-ENP14) were optimized with the help of Box-Behnken Design Expert software. The developed formulation (ENP2) was optimized based on the particle size (286 ± 3.67 nm), PDI (0.263 ± 0.01), and zeta potential (31.8 ± 3.18 mV). The optimized formulation (ENP2) exhibited a sustained release behavior with maximum drug release and followed the Higuchi model. The chronic restraint stress (CRS) was successfully used to develop the IBS-D rat model, which led to increased defecation frequency. The in vivo studies revealed a significant reduction in defecation frequency and disease activity index by ENP2 compared with pure ELD. Thus, the results demonstrated that the developed eudragit-based polymeric nanoparticles can act as a potential approach for the effective delivery of eluxadoline through oral administration for irritable bowel syndrome diarrhea treatment.

OBJECTIVE: Bile acid (BA) metabolism by intestinal bacteria is associated with the risk of gastrointestinal diseases; additionally, its control has become a modern strategy for treating metabolic diseases. This cross-sectional study investigated the influence of defecation status, intestinal microbiota, and habitual diet on fecal BA composition in 67 community-dwelling young participants.
METHODS: Feces were collected for intestinal microbiota and BA analyses; data about defecation status and dietary habits were collected using the Bristol stool form scales and a brief-type self-administered diet history questionnaire, respectively. The participants were categorized into four clusters based on their fecal BA composition, according to cluster analysis, and tertiles based on deoxycholic acid (DCA) and lithocholic acid (LCA) levels.
RESULTS: The high primary BA (priBA) cluster with high fecal cholic acid (CA) and chenodeoxycholic acid (CDCA) levels had the highest frequency of normal feces, whereas the second BA (secBA) cluster with high levels of fecal DCA and LCA had the lowest. Alternately, the high-priBA cluster had a distinct intestinal microbiota, with higher Clostridium subcluster XIVa and lower Clostridium cluster IV and Bacteroides. The low-secBA cluster with low fecal DCA and LCA levels had the lowest animal fat intake. Nevertheless, the insoluble fiber intake of the high-priBA cluster was significantly higher than that of the high-secBA cluster.
CONCLUSIONS: High fecal CA and CDCA levels were associated with distinct intestinal microbiota. Conversely, high levels of cytotoxic DCA and LCA were associated with increased animal fat intake and decreased frequency of normal feces and insoluble fiber intake.
BACKGROUND: University Hospital Medical Information Network (UMIN) Center system (UMIN000045639); date of registration: 15/11/2019.

This integrative aimed to evaluate the effects and the potential mechanism of action of prebiotics, probiotics, and synbiotics on constipation-associated gastrointestinal symptoms and to identify issues that still need to be answered. A literature search was performed in the PubMed database. Animal models (n = 23) and clinical trials (n = 39) were included. In animal studies, prebiotic, probiotic, and synbiotic supplementation showed a decreased colonic transit time (CTT) and an increase in the number and water content of feces. In humans, inulin is shown to be the most promising prebiotic, while B. lactis and L. casei Shirota probiotics were shown to increase defecation frequency, the latter strain being more effective in improving stool consistency and constipation symptoms. Overall, synbiotics seem to reduce CTT, increase defecation frequency, and improve stool consistency with a controversial effect on the improvement of constipation symptoms. Moreover, some aspects of probiotic use in constipation-related outcomes remain unanswered, such as the best dose, duration, time of consumption (before, during, or after meals), and matrices, as well as their effect and mechanisms on the regulation of inflammation in patients with constipation, on polymorphisms associated with constipation, and on the management of constipation via 5-HT. Thus, more high-quality randomized control trials (RCTs) evaluating these lacking aspects are necessary to provide safe conclusions about their effectiveness in managing intestinal constipation.

Constipation is a common problem in sows and women during late pregnancy. Dietary fiber has potential in the regulation of intestinal microbiota, thereby promoting intestinal motility and reducing constipation. However, the effects of fibers with different physicochemical properties on intestinal microbe and constipation during late pregnancy have not been fully explored. In this study, a total of 80 sows were randomly allocated to control and one of three dietary fiber treatments from day 85 of gestation to delivery: LIG (lignocellulose), PRS (resistant starch), and KON (konjaku flour). Results showed that the defecation frequency and fecal consistency scores were highest in PRS. PRS and KON significantly increased the level of gut motility regulatory factors, 5-hydroxytryptamine (5-HT), motilin (MTL), and acetylcholinesterase (AChE) in serum. Moreover, PRS and KON promoted the IL-10 level and reduced the TNF-α level in serum. Furthermore, maternal PRS and KON supplementation significantly reduced the number of stillborn piglets. Microbial sequencing analysis showed that PRS and KON increased short-chain fatty acids (SCFAs)-producing genera Bacteroides and Parabacteroides and decreased the abundance of endotoxin-producing bacteria Desulfovibrio and Oscillibacter in feces. Moreover, the relative abundance of Turicibacter and the fecal butyrate concentration in PRS were the highest. Correlation analysis further revealed that the defecation frequency and serum 5-HT were positively correlated with Turicibacter and butyrate. In conclusion, PRS is the best fiber source for promoting gut motility, which was associated with increased levels of 5-HT under specific bacteria Turicibacter and butyrate stimulation, thereby relieving constipation. Our findings provide a reference for dietary fiber selection to improve intestinal motility in late pregnant mothers.

Constipation is a condition of the digestive system characterized by formation of hard feces that are difficult to eliminate. It has emerged as a new problem that is commonly encountered by many people and lifestyle changes have been unsuccessful in providing a solution. This study aimed to investigate the effects of Lactobacillus paracasei subsp. paracasei NTU 101 on loperamide-induced constipated rats and on gastrointestinal tract function. Sprague-Dawley rats were administered loperamide (2 mg/kg BW) twice daily as well as 1.3, 2.6, and 13.0 mg/kg BW/rat/d of NTU 101 powder. The control, positive control, and NTU 101 powder groups (0.5, 1, 5×) showed improved intestinal mobility with a statistically significant increase of 12.4%, 14.7%, 12.5%, 13.4%, and 15.1%, respectively (p < 0.05); the fecal water content was also significantly increased by 11.7%, 9.0%, 10.0%, 9.3%, and 11.0%, respectively (p < 0.05), compared to the loperamide group. Furthermore, NTU 101 increased the Bifidobactrium spp. and decreased the Clostridium perfringens content in feces; it increased short-chain fatty acid levels, reduced fecal pH value, enhanced the thickness of the colonic mucosa, and increased the number of mucin-producing goblet cells and interstitial cells of Cajal. Thus, NTU 101 powder was found to alleviate loperamide-induced constipation and improve gastrointestinal tract function.

Synbiotics approach complementarily and synergistically toward the balance of gastrointestinal microbiota and improvement in bowel functions. A randomised, double-blind, placebo-controlled study was conducted to examine the effects of a synbiotics supplement among constipated adults. A total of 85 constipated adults, diagnosed by Rome III criteria for functional constipation were randomised to receive either synbiotics (n = 43) or placebo (n = 42) once daily (2.5 g) in the morning for 12 weeks. Eight times of follow-up was conducted every fortnightly with treatment response based on a questionnaire that included a record of evacuation (stool frequency, stool type according to Bristol Stool Form Scale), Patients Assessment on Constipation Symptoms (PAC-SYM), and Patients Assessment on Constipation Quality of Life (PAC-QOL). There were no significant differences in stool evacuation, but defecation frequency and stool type in treatment group were improved tremendously than in placebo group. While the treatment group was reported to have higher reduction in severity of functional constipation symptoms, the differences were not statistically significant. Dietary supplementation of synbiotics in this study suggested that the combination of probiotics and prebiotics improved the functional constipation symptoms and quality of life although not significant. This was due to the high placebo effect which synbiotics failed to demonstrate benefit over the controls.