Colonic Transit Time Research Articles

Spinal cord injury-induced neurogenic bowel: A role for host-microbiome interactions in bowel pain and dysfunction

Background and aimsSpinal cord injury (SCI) affects roughly 300,000 Americans with 17,000 new cases added annually. In addition to paralysis, 60% of people with SCI develop neurogenic bowel (NB), a syndrome characterized by slow colonic transit, constipation, and chronic abdominal pain. The knowledge gap surrounding NB mechanisms after SCI means that interventions are primarily symptom-focused and largely ineffective. The goal of the present studies was to identify mechanism(s) that initiate and maintain NB after SCI as a critical first step in the development of evidence-based, novel therapeutic treatment options. MethodsFollowing spinal contusion injury at T9, we observed alterations in bowel structure and function reflecting key clinical features of NB. We then leveraged tissue-specific whole transcriptome analyses (RNAseq) and fecal 16S rRNA amplicon sequencing in combination with histological, molecular, and functional (Ca2+ imaging) approaches to identify potential mechanism(s) underlying the generation of the NB phenotype. ResultsIn agreement with prior reports focused on SCI-induced changes in the skin, we observed a rapid and persistent increase in expression of calcitonin gene-related peptide (CGRP) expression in the colon. This is suggestive of a neurogenic inflammation-like process engaged by antidromic activity of below-level primary afferents following SCI. CGRP has been shown to disrupt colon homeostasis and negatively affect peristalsis and colon function. As predicted, contusion SCI resulted in increased colonic transit time, expansion of lymphatic nodules, colonic structural and genomic damage, and disruption of the inner, sterile intestinal mucus layer corresponding to increased CGRP expression in the colon. Gut microbiome colonization significantly shifted over 28 days leading to the increase in Anaeroplasma, a pathogenic, gram-negative microbe. Moreover, colon specific vagal afferents and enteric neurons were hyperresponsive after SCI to different agonists including fecal supernatants. ConclusionsOur data suggest that SCI results in overexpression of colonic CGRP which could alter colon structure and function. Neurogenic inflammatory-like processes and gut microbiome dysbiosis can also sensitize vagal afferents, providing a mechanism for visceral pain despite the loss of normal sensation post-SCI. These data may shed light on novel therapeutic interventions targeting this process to prevent NB development in patients.

Subtyping irritable bowel syndrome using cluster analysis: a systematic review

BackgroundIrritable bowel syndrome (IBS) is a common chronic functional gastrointestinal disorder associated with a wide range of clinical symptoms. Some researchers have used cluster analysis (CA), a group of non-supervised learning methods that identifies homogenous clusters within different entities based on their similarity.Objective and methodsThis literature review aims to identify published articles that apply CA to IBS patients. We searched relevant keywords in PubMed, Embase, Web of Science, and Scopus. We reviewed studies in terms of the selected variables, participants’ characteristics, data collection, methodology, number of clusters, clusters’ profiles, and results.ResultsAmong the 14 articles focused on the heterogeneity of IBS, eight of them utilized K-means Cluster Analysis (K-means CA), four employed Hierarchical Cluster Analysis, and only two studies utilized Latent Class Analysis. Seven studies focused on clinical symptoms, while four articles examined anocolorectal functions. Two studies were centered around immunological findings, and only one study explored microbial composition. The number of clusters obtained ranged from two to seven, showing variation across the studies. Males exhibited lower symptom severity and fewer psychological findings. The association between symptom severity and rectal perception suggests that altered rectal perception serves as a biological indicator of IBS. Ultra-slow waves observed in IBS patients are linked to increased activity of the anal sphincter, higher anal pressure, dystonia, and dyschezia.ConclusionIBS has different subgroups based on different factors. Most IBS patients have low clinical severity, good QoL, high rectal sensitivity, delayed left colon transit time, increased systemic cytokines, and changes in microbial composition, including increased Firmicutes-associated taxa and depleted Bacteroidetes-related taxa. However, the number of clusters is inconsistent across studies due to the methodological heterogeneity. CA, a valuable non-supervised learning method, is sensitive to hyperparameters like the number of clusters and random initialization of cluster centers. The random nature of these parameters leads to diverse outcomes even with the same algorithm. This has implications for future research and practical applications, necessitating further studies to improve our understanding of IBS and develop personalized treatments.

Cross-cultural adaptation and validation of the constipation scoring system for the pediatric population: A new tool to be used for constipated children

The Rome IV criteria are used to characterize constipation and its subtypes, but not its severity. Conversely, the constipation scoring system (CSS) is a tool designed to assess the level of constipation severity and assist clinicians in selecting suitable therapeutic strategies. Although validated for adults, this score has yet to be validated for children. To adapt and validate the CSS for the pediatric population. Children and adolescents of 4-17 years of age with no morphological or neurological abnormalities of the gastrointestinal system were randomly selected during general consultation with a pediatrician and evaluated between November 2021 to April 2022. The Rome IV criteria were considered the gold-standard detection method. The adapted version was initially assessed on 30 children to assess comprehension and then administered to another 100 children. The internal consistency of the adapted questionnaire was assessed in a test-retest procedure with a two-week interval. One hundred patients with a mean age of 8.61±3.25 years were assessed. Of these, 51 (51%) were male. Most children (n=91) received a score of 1-10 (the total CSS score can range from 0 to 30 points). The correlation between the pediatric version of the CSS and the Rome IV criteria was substantial, as shown by a positive Spearman correlation (r2) of 0.553 (p<0.001). Cronbach's alpha between the test-retest responses was 0.97. When each item of the questionnaire was assessed individually, a greater level of internal consistency was found, indicating adequate internal reliability. The current study broadens the horizon with the emergence of new diagnostic aid for FC in Brazilian children and adolescents. In addition, this study provides the cornerstone for future research to determine the diagnostic accuracy of the CSS and its prognostic value for monitoring the treatment. The loss of a follow-up rate (26%) during the telephone "test-retest" phase was a limitation. Using a subjective questionnaire such as the Rome IV criteria as the gold standard method may also represent a limitation. Further research is required on the use of objective diagnostic tools for FC including colonic transit time, anal manometry, cine-defecography, and electromyography. The CSS was successfully adapted for use with the pediatric population and was well accepted, confirming its language and psychometric validity in aiding the diagnosis of functional constipation. This was the first step towards validating the use of this score in other countries and cultures to assess the severity of constipation in children.

Gut microbiota response to in vitro transit time variation is mediated by microbial growth rates, nutrient use efficiency and adaptation to in vivo transit time

BackgroundTransit time is an important modulator of the human gut microbiome. The inability to modify transit time as the sole variable hampers mechanistic in vivo microbiome research. We singled out gut transit time in an unprecedented in vitro approach by subjecting faecal microbial communities from six individuals with either short, medium or long in vivo transit times, to three different colonic transit times of 21, 32 and 63 h in the validated human gut in vitro model, SHIME.ResultsTransit time was identified as the single most important driver of microbial cell concentrations (52%), metabolic activity (45%) and quantitative (24%) and proportional (22%) community composition. Deceleration of transit was characterised by a significant decrease of specific Bifidobacterium and Veillonella spp. and increase of specific fibre degrading bacteria and nutrient specialists, such as Bacteroides, Prevotella, Ruminococcus, Bilophila and Akkermansia spp. These microbial communities reached a higher population density and net carbohydrate fermentation, leading to an increased SCFA production at longer transit times. In contrast, the carbohydrate-to-biomass production efficiency was increased at shorter transits, particularly in well-adapted faecal microbiomes from donors with short in vivo transit. Said adaptation was also reflected in the carbohydrate-to-SCFA conversion efficiency which varied with donor, but also colon region and SCFA chain length. A long transit time promoted propionate production, whereas butyrate production and butyrate producers were selectively enriched in the proximal colon at medium transit time.ConclusionMicrobial growth rates and nutrient utilisation efficiency mediate the species-specific gut microbiota response to in vitro transit time variation, which is the main driver of in vitro microbial load, metabolism and community composition. Given the in vivo transit time variation within and between individuals, the personalisation of in vitro transit time based on in vivo data is required to accurately study intra- and inter-individual differences in gut microbiome structure, functionality and interactions with host and environmental modulators.1MQXL3e8MgVLC8CZ9wex6EVideo

Objective estimation of colonic transit time using radiopaque markers in an abdominal X-ray after laparoscopic colorectal resection: secondary analysis of a randomized clinical trial.

Objective estimation of colonic transit time using radiopaque markers in an abdominal X-ray after laparoscopic colorectal resection: secondary analysis of a randomized clinical trial.

Region-specific remodeling of the enteric nervous system and enteroendocrine cells in the colon of spinal cord injury patients

Patients with spinal cord injury (SCI) suffer from major bowel dysfunction, whose exact pathophysiology, particularly the involvement of the enteric nervous system or epithelial dysfunction is poorly understood. Herein, we aimed to characterize the mucosal biopsies of the right and left colon in SCI patients vs controls (CT): (1) remodeling of key enteric neurotransmitters, (2) remodeling of enteroendocrine cells, and (3) mucosal inflammation compared to those in controls. In SCI, mucosal ACh concentration was lower in the right colon as compared to CT, but no change was observed in the left colon, and AChE expression was lower in both the right and left colons than in CT. While the VIP concentration was similar in the right and left colons, VIP mRNA expression was increased in the right colon and decreased in the left colon, in SCI patients as compared to CT. Interestingly, 5-HT concentration was reduced in the left colon but not in the right colon in SCI patients. Moreover, in SCI patients, as compared to CT, SERT mRNA expression was selectively increased in the left colon while TPH1 mRNA expression was increased in the right and left colons. Although mucosal TNFα and IL-1β mRNA expression did not significantly differ between SCI and CT groups, we identified a significant positive correlation between TNFα and IL-1β mRNA expression and left colon transit time in the SCI group. In conclusion, region-specific changes occur in the enteric neurotransmitter, serotonergic, and inflammatory pathways in the colon of SCI patients. The significant correlations between these pathways and clinical parameters in the left colon further set a scientific basis for designing therapeutic targets to improve colonic motor dysfunction in patients.Biobank information: Spinal cord injury patients: PHRC ConstiCAPE—clinical trial NCT02566746. Controls: Anosain—clinical trial NCT03054415 and biobank of the “Institut des Maladies de l’Appareil Digestif (IMAD)” registered under number DC-2008-402.

PENGARUH PIJAT BAYI TERHADAP KONSTIPASI PADA BAYI USIA 1 - 12 BULAN DI PMB A TAHUN 2023

Constipation is a symptom of difficult bowel movements which is characterized by the consistency of hard stools, large size and decreased frequency of bowel movements. Constipation can cause social and psychological problems. Treatment for constipation is to get used to defecating regularly by means of behavior modification, fiber diet, laxatives, and psychological approaches. Massage provides benefits for constipation by stimulating peristalsis and reducing colonic transit time so that it can increase the frequency of bowel movements. The research design uses a pre-experiment, using a static group comparison research design or a comparison with static groups. Results were analyzed using Univariate and Bivariate using the Chy Square test. Based on the results of my research, it can be seen that out of 15 cases of babies who underwent massage therapy, 2 babies (13.3%) had difficult bowel movements, while 13 babies (86.7%) had smooth bowel movements. According to the researcher's assumption, there is no gap between the results of this study and the theory. Baby massage therapy greatly affects the smooth process of defecation. By doing baby massage techniques can facilitate bowel movements.

Gastrointestinal Sensory Neuropathy and Dysmotility in Fabry Disease: Presentations and Effect on Patient's Quality of Life.

Fabry disease is a rare multisystemic lysosomal disease resulting in variable manifestations of the gastrointestinal (GI), neurologic, cardiac, and renal systems. Whether GI manifestations are a result of gut dysmotility is undetermined. We aimed to explore GI manifestations in depth and their effect on patients with Fabry disease and to characterize gut motility. We recruited adult patients with Fabry disease reporting GI manifestations. All patients answered a battery of questionnaires covering symptom severity, GI-specific quality of life, and effects of work/productivity and underwent a wireless motility capsule test to measure pan-gut motility. In 48 patients with Fabry disease, abnormal bowel habits and abdominal pain were the most common symptoms. Bloating, nausea, vomiting, and reflux were also prevalent. Neurologic manifestations were found in 95.8% of patients, along with their GI manifestations. Dysmotility was found in less than 35% of wireless motility capsule tests. Colon transit time was associated with constipation severity and Bristol Stool Scale. Several GI symptoms were associated with reduced quality of life, anxiety, and work/productivity, but not Fabry severity score. This is the largest study of GI manifestations in patients with Fabry disease that characterizes gut motility. We found little association between GI manifestations and motility indices, suggesting that visceral hypersensitivity may be a major driver of symptoms. GI symptoms affect different aspects of patients' lives, yet are not always well-discussed or optimally managed in Fabry disease. Disease severity scores when used for therapeutic decision making do not often include GI symptoms or their impact.

Gastrointestinal Transit Times in Health as Determined Using Ingestible Capsule Systems: A Systematic Review.

Ingestible capsule (IC) systems can assess gastrointestinal (GI) transit times as a surrogate for gut motility for extended periods of time within a minimally invasive, radiation-free and ambulatory setting. A literature review of IC systems and a systematic review of studies utilizing IC systems to measure GI transit times in healthy volunteers was performed. Screening for eligible studies, data extraction and bias assessments was performed by two reviewers. A narrative synthesis of the results was performed. The literature review identified 23 different IC systems. The systematic review found 6892 records, of which 22 studies were eligible. GI transit time data were available from a total of 1885 healthy volunteers. Overall, seventeen included studies reported gastric emptying time (GET) and small intestinal transit time (SITT). Colonic transit time (CTT) was reported in nine studies and whole gut transit time (WGTT) was reported in eleven studies. GI transit times in the included studies ranged between 0.4 and 15.3 h for GET, 3.3-7 h for SITT, 15.9-28.9 h for CTT and 23.0-37.4 h for WGTT. GI transit times, notably GET, were influenced by the study protocol. This review provides an up-to-date overview of IC systems and reference ranges for GI transit times. It also highlights the need to standardise protocols to differentiate between normal and pathological function.

High Prevalence of Anorectal Dysfunction in Ambulatory Patients with Chronic Constipation, Regardless of Colon Transit Time.

Classification of chronic constipation (CC) into its three subtypes of slow transit constipation, defecation disorder and normal transit constipation, may improve its multifaceted management. We assessed the merits of the London classification in patients with CC, who were studied by both wireless motility capsule (WMC) and high-resolution anorectal manometry (HR-ARM), examining their relative utilities in decision-making.s PATIENTS AND METHODS: Retrospective, community-based study of prospectively collected data on patients with CC by Rome IV criteria, who underwent WMC and HR-ARM, Balloon Expulsion Test, and Rectal Sensory Testing. Clinical assessment was made by standard questionnaires. On WMC, standard criteria for colonic transit time (CTT) were used (normal CTT < 59h). The hierarchical London classification was used for HR-ARM analyses. Of 1261 patients with CC, 166 (91M; ages 22-86) received technically satisfactory WMC and HR-ARM, formed the analyzed study cohort, of whom 84 had normal CTT and 82 had prolonged CTT (> 59h). Patients with slow CTT were significantly older and had longer duration and more severe disease. Using the London classification criteria for disorders of anorectal function, we noted a high prevalence of anorectal dysfunction, regardless of CTT. Except for lower rate of anal hypertonicity in patients with slow CTT, disorders of recto-anal coordination, and rectal sensation were seen at a comparable rate in patients with CC, regardless of CTT. There is a significant overlap of anorectal disorders in patients with slow CTT. There is questionable specificity and utility of WMC and HR-ARM in assessing patients with CC. More work is needed to demonstrate the value of these studies as surrogate markers of the disease and its response to multifaceted therapy.

Exploring the Facts Regarding Colon Transit Study in Children

Aim: Constipation is a problem faced by many children around the world. There are different ways of diagnosis and management of this condition. The key to the right diagnosis is based on the series of investigation that differs with children. The subject of interest is often the amount of time it takes for a substance to move through the colon which is known as Colon Transit Time [CTT]. Colon transit study or radio-opaque marker [ROM] study otherwise known as pellet study is one of the first choices of treatment to identify the CTT. Describing the colon transit study based on the established findings is the aim of this study.&#x0D; Methods: The MeSH terms used for literature retrieval were ‘marker studies in children’, ‘pellet study in children’, ‘colon transit study in children’. The retrieval was performed based on pubmed, EMBASE, Web of Science as well as official websites. The search found 31 studies published from 2002 to 2022, as being met the inclusion criteria.&#x0D; Results: The existing studies have identified a systematic way of performing the colon transit studies in children in many different ways. The colon transit differs with the segment of the colon and the age group of children.&#x0D; Conclusion: Although the colon transit study requires series of intervention and investigation, the exact way of performing the same depends on the policies and protocols adopted by the individual specialist health care setting.

Associations Between Physical Activity and Gastrointestinal Transit Times in People with Normal Weight, Overweight, and Obesity

BackgroundRapid gastric emptying is associated with obesity and overeating, whereas delayed gastric emptying is associated with anorexia. Acute effects of exercise on gastric emptying have been investigated extensively, but the influence of habitual physical activity on gastric emptying and transit time in other regions of the gastrointestinal tract is poorly understood. ObjectiveThe objective was to investigate associations between objectively measured habitual physical activity and gastrointestinal transit times in adults with varying degrees of adiposity. Methods50 adults (58% women) were included in this cross-sectional study. Physical activity was measured by an accelerometer placed on the lower back for 7 d. Gastric emptying time, small bowel transit time, colonic transit time, and whole gut transit time were simultaneously evaluated by a wireless motility capsule, which was ingested together with a standardized mixed meal. Linear regression models were applied to assess the associations of total activity counts and time spent at different intensities—sedentary activity (0–100 counts/min), low light activity (101–759 counts/min), high light activity (760–1951 counts/min); moderate and vigorous activity (≥1952 counts/min)) with gastrointestinal transit times. ResultsMedian [Q1; Q3] age was 56.5 [46.6–65.5] y, and body mass index (BMI) was 32.1 [28.5–35.1] kg/m2. For every additional hour spent performing high light intensity physical activity, colonic transit time was 25.5 % [95% CI: 3.10, 42.7] more rapid (P = 0.028), and whole gut transit time was 16.2 % [95% CI: 1.84, 28.4] more rapid (P = 0.028) when adjusted for sex, age, and body fat. No other associations were observed. ConclusionsMore time spent on physical activity at high light intensity was associated with more rapid colonic and whole gut transit time, independent of age, sex, and body fat, whereas other intensities of physical activity and gastrointestinal transit times were not associated. Trial registrationClinicaltrials.gov IDs (NCT03894670, NCT03854656).

SmartPill™ Administration to Assess Gastrointestinal Function after Spinal Cord Injury in a Porcine Model-A Preliminary Study.

Gastrointestinal (GI) complications, including motility disorders, metabolic deficiencies, and changes in gut microbiota following spinal cord injury (SCI), are associated with poor outcomes. After SCI, the autonomic nervous system becomes unbalanced below the level of injury and can lead to severe GI dysfunction. The SmartPill™ is a non-invasive capsule that, when ingested, transmits pH, temperature, and pressure readings that can be used to assess effects in GI function post-injury. Our minipig model allows us to assess these post-injury changes to optimize interventions and ultimately improve GI function. The aim of this study was to compare pre-injury to post-injury transit times, pH, and pressures in sections of GI tract by utilizing the SmartPill™ in three pigs after SCI at 2 and 6 weeks. Tributyrin was administered to two pigs to assess the influences on their gut microenvironment. We observed prolonged GET (Gastric Emptying Time) and CTT (Colon Transit Time), decreases in contraction frequencies (Con freq) in the antrum of the stomach, colon, and decreases in duodenal pressures post-injury. We noted increases in Sum amp generated at 2 weeks post-injury in the colon, with corresponding decreases in Con freq. We found transient changes in pH in the colon and small intestine at 2 weeks post-injury, with minimal effect on stomach pH post-injury. Prolonged GETs and CTTs can influence the absorptive profile in the gut and contribute to pathology development. This is the first pilot study to administer the SmartPill™ in minipigs in the context of SCI. Further investigations will elucidate these trends and characterize post-SCI GI function.

Using deep learning–derived image features in radiologic time series to make personalised predictions: proof of concept in colonic transit data

ObjectivesSiamese neural networks (SNN) were used to classify the presence of radiopaque beads as part of a colonic transit time study (CTS). The SNN output was then used as a feature in a time series model to predict progression through a CTS.MethodsThis retrospective study included all patients undergoing a CTS in a single institution from 2010 to 2020. Data were partitioned in an 80/20 Train/Test split. Deep learning models based on a SNN architecture were trained and tested to classify images according to the presence, absence, and number of radiopaque beads and to output the Euclidean distance between the feature representations of the input images. Time series models were used to predict the total duration of the study.ResultsIn total, 568 images of 229 patients (143, 62% female, mean age 57) patients were included. For the classification of the presence of beads, the best performing model (Siamese DenseNET trained with a contrastive loss with unfrozen weights) achieved an accuracy, precision, and recall of 0.988, 0.986, and 1. A Gaussian process regressor (GPR) trained on the outputs of the SNN outperformed both GPR using only the number of beads and basic statistical exponential curve fitting with MAE of 0.9 days compared to 2.3 and 6.3 days (p < 0.05) respectively.ConclusionsSNNs perform well at the identification of radiopaque beads in CTS. For time series prediction our methods were superior at identifying progression through the time series compared to statistical models, enabling more accurate personalised predictions.Clinical relevance statementOur radiologic time series model has potential clinical application in use cases where change assessment is critical (e.g. nodule surveillance, cancer treatment response, and screening programmes) by quantifying change and using it to make more personalised predictions.Key Points• Time series methods have improved but application to radiology lags behind computer vision. Colonic transit studies are a simple radiologic time series measuring function through serial radiographs.• We successfully employed a Siamese neural network (SNN) to compare between radiographs at different points in time and then used the output of SNN as a feature in a Gaussian process regression model to predict progression through the time series.• This novel use of features derived from a neural network on medical imaging data to predict progression has potential clinical application in more complex use cases where change assessment is critical such as in oncologic imaging, monitoring for treatment response, and screening programmes.

Regulation of enteric nervous system via sacral nerve stimulation in opioid-induced constipated rats.

Sacral nerve stimulation (SNS) has been employed for treating constipation. However, its mechanisms involving enteric nervous system (ENS) and motility are largely unknown. In this study, we investigated the possible ENS involvement of SNS in treating Loperamide-induced constipation in rats. Experiment-1 was designed to study the effects of acute SNS on whole colon transit time (CTT). In experiment-2, we induced constipation by Loperamide and then applied daily SNS or sham-SNS for 1 week. Choline acetyltransferase (ChAT), nitric oxide synthase (nNOS), and PGP9.5 in colon tissue were examined at the end of the study. Moreover, survival factors such as phosphorylated AKT (p-AKT) and Glial cell-derived neurotrophic factor (GDNF) were measures by immunohistochemistry (IHC) and western blot (WB). (1) SNS with one set of parameters shortened CTT starting at 90 min after phenol red administration (p < 0.05). (2) While Loperamide induced slow transit constipation with a significant reduction in fecal pellet number and feces wet weight, daily SNS for a week resolved constipation. (3) Moreover, SNS was able to shorten whole gut transit time comparing to sham-SNS (p = 0.01). (4) Loperamide reduced the number of PGP9.5 and ChAT positive cells, and downregulated ChAT protein expression and upregulated nNOS protein expression, whereas these detrimental effects were significantly reversed by SNS. (5) Furthermore, SNS increased expressions of both GDNF and p-AKT in colon tissue. (6) Vagal activity was reduced following Loperamide (p < 0.01); yet SNS normalized vagal activity. SNS with appropriate parameters improves opioid-induced constipation and reversed the detrimental effects of Loperamide on enteric neurons possibly via the GDNF-PI3K/Akt pathway.GRAPHICAL ABSTRACT.

Effects of a wholegrain-rich diet on markers of colonic fermentation and bowel function and their associations with the gut microbiome: a randomised controlled cross-over trial.

Diets rich in whole grains are associated with health benefits. Yet, it remains unclear whether the benefits are mediated by changes in gut function and fermentation. We explored the effects of whole-grain vs. refined-grain diets on markers of colonic fermentation and bowel function, as well as their associations with the gut microbiome. Fifty overweight individuals with increased metabolic risk and a high habitual intake of whole grains (~69 g/day) completed a randomised cross-over trial with two 8-week dietary intervention periods comprising a whole-grain diet (≥75 g/day) and a refined-grain diet (<10 g/day), separated by a washout period of ≥6 weeks. A range of markers of colonic fermentation and bowel function were assessed before and after each intervention. The whole-grain diet increased the levels of faecal butyrate (p = 0.015) and caproate (p = 0.013) compared to the refined-grain diet. No changes in other faecal SCFA, BCFA or urinary levels of microbial-derived proteolytic markers between the two interventions were observed. Similarly, faecal pH remained unchanged. Faecal pH did however increase (p = 0.030) after the refined-grain diet compared to the baseline. Stool frequency was lower at the end of the refined-grain period compared to the end of the whole-grain diet (p = 0.001). No difference in faecal water content was observed between the intervention periods, however, faecal water content increased following the whole-grain period compared to the baseline (p = 0.007). Dry stool energy density was unaffected by the dietary interventions. Nevertheless, it explained 4.7% of the gut microbiome variation at the end of the refined-grain diet, while faecal pH and colonic transit time explained 4.3 and 5%, respectively. Several butyrate-producers (e.g., Faecalibacterium, Roseburia, Butyriciococcus) were inversely associated with colonic transit time and/or faecal pH, while the mucin-degraders Akkermansia and Ruminococcaceae showed the opposite association. Compared with the refined-grain diet, the whole-grain diet increased faecal butyrate and caproate concentrations as well as stool frequency, emphasising that differences between whole and refined grains affect both colonic fermentation and bowel habits.

Vitamin A deficiency from maternal gestation may contribute to autistic-like behaviors and gastrointestinal dysfunction in rats through the disrupted purine and tryptophan metabolism

Vitamin A deficiency (VAD) has been linked to autism spectrum disorder (ASD) in multiple studies, and autistic children with gastrointestinal (GI) symptoms have been found to have lower VA levels than those without GI symptoms. However, the exact mechanism by which VAD causes both core symptoms and GI symptoms in ASD is ill defined. We constructed VAD and vitamin A normal (VAN) rat models from maternal gestation onwards. Autism-related behaviors were tested using the open-field test and the three-chamber test, and GI function was assessed with the GI transit time, the colonic transit time and fecal water content. Untargeted metabolomic analysis on the prefrontal cortex (PFC) and fecal samples was performed. VAD rats displayed autistic-like behaviors and impaired GI function compared to VAN rats. Metabolic profiles of both PFC and feces from VAD and VAN rats were significantly different. The differential metabolites in both PFC and feces between the VAN and VAD rats were mostly enriched in the purine metabolic pathway. Moreover, the most significantly affected metabolic pathway in PFC of VAD rats was the phenylalanine, tyrosine and tryptophan biosynthesis pathway, and the most remarkably altered metabolic pathway in the feces of VAD rats was the tryptophan metabolism pathway. These results indicate that VAD starting from maternal gestation might be linked to core symptoms of ASD and its GI co-occurring disorders through the purine and tryptophan-related metabolism disorders.

The effect of polydextrose on fecal bulk and bowel function in mildly constipated healthy adults: a double-blind, placebo controlled study

Background &amp; Aims. Polydextrose (PDX) (8-30g/day) has been reported to increase faecal bulk and consistency, leading to easier stool passage. However, studies on its effect on defaecation frequency and colonic transit time have provided mixed results, and most focused on either healthy or highly constipated adults, leaving the question on if and how PDX could also aid mildly constipated individuals partially unanswered.Methods. We investigated the effects of PDX consumption by healthy subjects experiencing one or more symptoms of mild constipation on faecal bulk, defaecation frequency, stool consistency, ease of stool passage, and total colonic transit time to further characterize and generate additional evidence regarding the potential beneficial effects of this fibre. 51 subjects participated in a 4-week, two-center, randomized, double-blind, placebo-controlled, parallel study testing a control (CON) and a PDX treatment (18 g/d included in biscuits and drink mixtures) (registered on clinicaltrials.gov with the identifier" NCT05309837").Results. Consumption of PDX resulted in 120.7 g and 25.7 g higher faecal wet and dry weight, respectively (p &lt; 0.05). Colonic transit time was ~4 h shorter in the PDX group: although this difference did not reach significance (p &gt; 0.05) as the study was underpowered to detect a statistical difference for this secondary outcome, this result still carries a physiological importance. Consumption of PDX was well-tolerated, with some PDX volunteers reporting more mild flatulence (p &lt; 0.05).Conclusions. All in all, our study adds new evidence on how a moderate (18g) daily intake of PDX could increase faecal bulking and potentially shorten colonic transit time, making this ingredient a good candidate to be used to formulate, and reformulate, foods and beverages by replacing caloric carbohydrates with reduced caloric content, enriching food items easily consumed to enhance fibre intake and support bowel function.

Interferential therapy for chronic constipation in adults: The CON-COUR randomizedcontrolled trial.

Chronic constipation (CC) is a frequent condition, and the first-line treatment includes dietary rules, the use of laxatives, and biofeedback for evacuation disorders. However, almost half of the patients are dissatisfied with their current treatment. We report the first double-blind randomized multicenter trial assessing the effectiveness of transabdominal electrical stimulation by interferential therapy (IFT) in the treatment of CC in adults. A prospective, multicenter, randomized, double-blind, sham-controlled, parallel-group, phase 3 trial was conducted at 7 centers in France. The primary endpoint was 8-week efficacy as defined by the number of complete spontaneous bowel movements during the last 4weeks of the 8-week stimulation period. Secondary endpoints included the evaluation of the effects of IFT on symptoms (Patient Assessment of Constipation Symptoms questionnair (PAC-SYM)), quality of life (QOL) (Patient Assessment of Constipation Quality of Life), Colonic transit time (CTT), anorectal manometry, and patient satisfaction. The proportion of 8-week responders was not significantly different between the two groups (73.2% in the IFT group vs. 67.1% in the sham group). After 8weeks of stimulation, the mean overall PAC-SYM score and the mean reduction in the overall PAC-SYM score were significantly greater in the IFT group than in the sham group. No differences were observed concerning CTT, anorectal manometry, or patient satisfaction. Although the primary endpoint was not reached, IFT can significantly alleviate the symptoms and improve the QOL of CC patients. It can be assumed that new treatments require different modes of evaluation and that the assessment of patient-reported outcomes may become a priority among therapeutic targets of CC. Trial registration number NCT02381665.

Evaluation of Gastrointestinal Symptoms in an ALS Cohort (P10-8.007)

<h3>Objective:</h3> The aim in this study is to understand the frequency of gastrointestinal symptoms in persons with ALS and relationship to disease duration and severity. <h3>Background:</h3> Amyotrophic Lateral Sclerosis is a disorder of motor neurons in which involvement of the enteric nervous system (ENS) has been implicated. Delayed gastric emptying and slowing of colonic transit time are reported. These symptoms impact the use of anticholinergic agents for treatments and offer opportunities for interventions that improve quality of life. <h3>Design/Methods:</h3> Patients diagnosed with ALS were recruited from the MDA/ALS Center of Hope Clinic at Temple University and healthy control volunteers were accepted. Patient Assessment of GI symptoms (GI-SYM) and Patient Assessment of Constipation (PAC-SYM) questionnaires are patient reported severity of symptoms over a 2-week history on an ordinal level. ALS Functional Rating Scale – Revised (ALSFRS-R), a 12-item questionnaire, assesses functional disability across 4 domains: bulbar, fine motor, gross motor and respiratory. Data was analyzed using IBM SPSS Statistics software. <h3>Results:</h3> 31 subjects are enrolled in the study with 12 controls and 19 ALS cases. The median(IQR) GI-SYM, PAC-SYM, and ALSFRS-R scores were 4.5(8), 1(4.75), and 42.5(15), respectively. A two-tailed t test, assuming unequal variances, revealed significant differences in PAC-SYM scores between healthy controls and ALS cases (t(23.22) = −2.17, p = 0.041). Spearman Rank Correlation revealed positive correlation between GI-SYM and PAC-SYM (r(26) = 0.70, p &lt; 0.001) and negative correlation between ALSFRS-R and GI-SYM (r(26) = −0.44, p = 0.019). <h3>Conclusions:</h3> In this preliminary study, the 2-week history GI-SYM questionnaire negatively correlated with ALSFRS-R scores and there was significant difference in PAC-SYM scores between healthy controls and ALS cases, suggesting potential enteric nervous system involvement. Recent evidence of brain-gut interaction, importance of the ENS, and the role of the microbiome in ALS and other neurodegenerative diseases suggests these symptoms are in part disease related. <b>Disclosure:</b> Dr. Empeno has nothing to disclose. Mr. Furey has nothing to disclose. Dr. Heiman-Patterson has received personal compensation in the range of $500-$4,999 for serving as a Consultant for ITF. Dr. Heiman-Patterson has received personal compensation in the range of $500-$4,999 for serving as a Consultant for MTPA. Dr. Heiman-Patterson has received personal compensation in the range of $500-$4,999 for serving as a Consultant for Samus. Dr. Heiman-Patterson has received personal compensation in the range of $500-$4,999 for serving on a Scientific Advisory or Data Safety Monitoring board for MTPA. Dr. Heiman-Patterson has received personal compensation in the range of $500-$4,999 for serving on a Scientific Advisory or Data Safety Monitoring board for Biogen. Dr. Heiman-Patterson has received personal compensation in the range of $500-$4,999 for serving on a Scientific Advisory or Data Safety Monitoring board for Amylym. Dr. Heiman-Patterson has received personal compensation in the range of $500-$4,999 for serving on a Scientific Advisory or Data Safety Monitoring board for Biohaven. Dr. Heiman-Patterson has received personal compensation in the range of $500-$4,999 for serving on a Scientific Advisory or Data Safety Monitoring board for Cytokinetics.