Bristol Stool Form Scale Research Articles

AN OPEN LABELLED CLINICAL TRIAL TO EVALUATE THE EFFICACY OF MATRA BASTI WITH SUKUMARA GHRITA FOLLOWED BY THE ADMINISTRATION OF VAISHWANARA CHURNA IN THE MANGEMENT OF VIBANDHA VIS-A-VIS CONSTIPATION IN GERIATRIC AGE GROUP

Background: Constipation is a frequently reported bowel symptom in the elderly with considerable impact on quality of life and health expenses. Disease-related morbidity and even mortality have been reported in the affected frail elderly. Although constipation is not a physiologic consequence of normal aging, decreased mobility, medications, underlying diseases, and rectal sensory-motor dysfunction may all contribute to its increased prevalence in older adults. Direct and explicit description of Vibandha as a disease is not found in Ayurveda but different presentation of Purisha like Baddha Purisha, Ghana Purisha/Grathita Purisha, Sushka Purisha, Mala avabaddhata are found in different contexts of Ayurveda, these can be taken as various manifestations of Vibandha Objective Of The Study: To evaluate the effect of Matra basti with Sukumara ghrita, followed by the administration of Vaishwanara churna with ghrita in the management of Vibandha vis-a-vis constipation in geriatric population. Methods: A clinical study with pre-post design. Data was collected on before intervention ie 0 day,mid intervention ,after matrabasti ie 9th day and and after the complete course of intervention,after internal administration of vaishwanara churna ie on 31 st day.The data obtained were analysed statistically by applying descriptive statistics,Paired t test and Chi square test,using statistical presentation system software (SPSS) for windows. Intervention:Matra basti with sukumara ghrita for the first 8 consecutive days of intervention in the dose of 60 ml. After Matra basti, Vaishwanara churna with ghrita as anupana was administered internally in the dosage of 12 gms in two equally divided doses, before food, for 22 days. Total duration of the study was 30 days Bristol Stool form scale and Patient assessment of constipation-Quality of life were used to assess the pre and post data gathered through pre designed research proforma.The results having ‘p’ value of <0.001 was considered to be statistically highly significant in this study. Results: Overall assessment showed significant improvement in all the 32 subjects in this study. Interpretation and Conclusion: It can be concluded that Matra basti with sukumara ghrita followed by internal administration of Vaishwanara churna showed better results in Bristol Stool form scale and Patient assessment of constipaion- Quality of life.

Artificial Intelligence Evaluation of Stool Quality Guides Management of Hepatic Encephalopathy Using a Smartphone App.

Lactulose-based hepatic encephalopathy treatment requires bowel movements/day titration, which is improved with Bristol stool scale (BSS) incorporation. Dieta app evaluates artificial intelligence (AI)-based BSS (AI-BSS) with stool images. Initially, controls (N = 13) and cirrhosis patients on lactulose/not on lactulose (n = 33) were trained on the app. They entered self-reported BSS (self-BSS) with AI-BSS communicated. Lactulose dose changes were tracked. A subset (n = 12) was retested with AI communication blocked. Most subjects were comfortable with the app. Self/AI-BSS and lactulose dose/AI-BSS correlation increased with app use. AI-BSS communications improved insight into self-BSS over time. Dieta app to gauge stool AI characteristics was acceptable and increased insight into lactulose dose and BSS in cirrhosis.

Long-term consequences of COVID-19 in patients with functional bowel disorders, rehabilitation prospective of microbiocenosis-oriented therapy

To analyze long-term consequences of the new coronavirus infection and rehabilitation prospective of microbiocenosis-oriented therapy in patients with functional bowel disorders. The study enrolled 100 consecutive patients with various types of functional bowel disorders with recurrence of symptoms after the new coronavirus infection. The severity of abdominal pain was evaluated in points, and bowel movement disorders were assessed using the Bristol stool scale. A questionnaire was used as part of an in-depth clinical examination for COVID-19 survivors to identify the clinical symptoms typical for the post-COVID syndrome. The Hospital Anxiety and Depression Scale was used to identify and assess the severity of depression and anxiety, and the Asthenic State Scale was used to diagnose the asthenia. All patients in the study subjectively linked the recurrence of bowel disorders with the new coronavirus infection. The most common bowel disorder was irritable bowel syndrome with diarrhea. A distinctive feature of exacerbations of intestinal symptoms in the post-COVID period is their association with depression/anxiety and asthenic states. The addition of Zakofalk® metaprebiotic to the treatment regimen was associated with significant regression of abdominal pain and normalization of bowel movement, an improvement of asthenia, anxiety, and depression. The addition of Zakofalk® to treatment regimens for exacerbations of functional bowel disorders after the new coronavirus infection significantly improves the effectiveness of therapy.

Assessment of pain intensity and methods of its relief in patients with irritable bowel syndrome

Objective — to develop a questionnaire for assessing the condition of patients with irritable bowel syndrome (IBS); to evaluate clinical effectiveness of personalized diet, synthetic agonist of peripheral opioid receptors m‑, k‑, and d‑ trimebutine maleate, and complex pro‑prebiotic drug (Lactobacillus acidophilus 500 million, Lactobacillus rhamnosus 1 billion, Sacchromyces boulardii 30 million, Bifidobacterium lactis 275 million, Bifidobacterium longum 1 billion, Clostridium butyricum 2 million, Bacillus clausii spores 2 billion, Fructo oligosaccharides 100 mg) in patients with IBS.
 Materials and methods. To evaluate the clinical effectiveness of the treatment, 28 patients with IBS have been examined. The investigated group included 15 (53.6%) patients with IBS and diarrhea, 11 (39.3%) subjects with mixed IBS, and two (7.1%) patients with IBS and constipation. The age of the patients was 32.5±3.1 years; from them 17 (51.7%) were women and 11 (39.3%) men. Nine women (52.9%) and five (45.5%) men were married, and 11 (64.7%) women and 7 (63.3%) men had higher education. The average duration of the disease in women was 3.4±1.8 years, and 3.1±1.5 years in men. The diagnosis of IBS was established according to the Rome criteria IV revision. Defecation was evaluated according to the Bristol stool scale. All patients filled out the «Questionnaire for a patient with irritable bowel syndrome» before the treatment start and during the treatment. The examined patients were prescribed a personalized diet with account their nutritional status, and drug therapy that included trimebutine maleate (film‑coated tablets) in a dose of 200 to 600 mg depending on pain intensity, and synbiotic (Lactobacillus acidophilus, Lactobacillus rhamnosus, Sacchromyces boulardii, Bifidobacterium lactis, Bifidobacterium longum, Clostridium butyricum, Bacillus clausii spores, Fructo oligosaccharides) in a dose of one capsule twice a day, regardless of the severity of the pain syndrome.
 Results. Complex treatment with the use of personalized dietary recommendations, synthetic agonist of peripheral opioid receptors trimebutine maleate and synbiotic that included Lactobacillus acidophilus, Lactobacillus rhamnosus, Sacchromyces boulardii, Bifidobacterium lactis, Bifidobacterium longum, Clostridium butyricum, Bacillus clausii spores, Fructo oligosaccharides, promoted to the decrease of pain syndrome severity, improvement of the psychoemotional state and quality of life of patients.
 Conclusions. The developed questionnaire for a patient with IBS was comprehensible and easy to fill out by patients; it allowed a practitioner to quickly analyze the dynamics of the pain syndrome. Personalized dietary treatment, a differentiated approach in administration of the peripheral opioid receptor agonist trimebutine maleate and synbiotics (Lactobacillus acidophilus, Lactobacillus rhamnosus, Sacchromyces boulardii, Bifidobacterium lactis, Bifidobacterium longum, Clostridium butyricum, Bacillus clausii spores, IBS oligosaccharides) was clinically effective for patients with IBS, it promoted the significant pain relief and improvement of the quality of life of patients.

Effect of dopaminergic therapy on lacrimation in Parkinson's disease

The prevalence of dry eye syndrome (DES) in Parkinson's disease (PD) reaches 87% and leads to impaired quality of life in many patients.Objective: to evaluate the lacrimal function and the effect of dopaminergic therapy in patients with PD.Material and methods: 43 patients with stage II–III PD according to Hoehn and Yahr (H&Y) receiving therapy with levodopa (n=17), amantadines (n=13) and dopamine receptor agonists (ADR) (n=28) were assessed using Schirmer's test (to estimate tear flow), sialometry, Unified Parkinson's Disease Rating Scale (UPDRSI-IV), Schwab and England Activities of Daily Living scale (Sch&En), the Parkinson’s Disease Questionnaire Summary Index (PDQ-39), the Mini Mental State Examination Scale (MMSE), the Non-Motor Symptom Questionnaire (NMSQ), the American Urological Association Symptom Scale (AUA), the Gastrointestinal Symptom Rating Scale (GSRS), the Bristol Stool Form Scale (BSFS).Results. Lacrimal insufficiency was found in 49% of patients. It occurred more frequently (χ2=9.546; p=0.003) in patients taking amantadine and correlated with the daily dose of amantadine (r-S=-0.359). It did not depend on the intake of ADR and levodopa and their doses but correlated with the UPDRS-IV score (r-S= -0.463), namely with the presence and duration of OFF-periods. Lacrimal insufficiency correlated with the Sch&En score (r-S=0.321) and non-motor parameters: UPDRSI (r-S =-0.302), NMSQ (r-S=-0.435), constipation domain of the GSRS (r-S=-0.362), BSFS (r-S=0.363). It was not related to age, gender, stage and duration of PD, motor symptoms of parkinsonism (assessed during the ON-phase) and was not related to salivation (although it was reduced in 39.5% of patients).Conclusion. Lacrimal insufficiency is observed in half of patients with stage II–III PD; it is related to the presence and duration of OFF-periods, the severity of other autonomic disorders and the use of amantadines, suggesting the role of dopamine dysregulation, neurodegeneration of autonomic centers and anticholinergic therapy in the development of DES in PD.

Effects of a Nutraceutical Multicompound, with Probiotics, Hericium, PEA, and Undaria in Patients with Irritable Bowel Syndrome

Irritable bowel syndrome (IBS) is a functional gastrointestinal condition. Probiotics and other nutraceutical compounds can have specific indications in the context of IBS. A retrospective analysis was conducted on 123 IBS patients in order to evaluate the effects of an oral probiotic-based dietary supplement (Colicron, one cps/day for 4 wk) on stool consistency and pain intensity. Different time points were defined as follows: baseline (T0), 2 wk of treatment (T2), and 4 wk of treatment (T4). Stool consistency was assessed by using the Bristol Stool Scale. Pain intensity was evaluated by the Visual Analogue Scale (VAS). Patients who were initially categorized as normal retained regular bowel movements throughout the study. Both patients with constipation and diarrhea showed an improvement in the Bristol Stool Scale. The score increased from 1.5 ± 0.5 to 3.3 ± 0.7 (p < 0.001) and decreased from 6.5 ± 0.7 to 4.3 ± 0.9 (p < 0.001) at T4, respectively, compared to T0. The VAS score for pain in the pooled IBS patients improved from 6.7 ± 2.2 to 2.8 ± 1.9 at T0 vs T4 (p < 0.001), with a similar trend also observed when patients were categorized based on stool consistency: normal (from 5.2 ± 1.9 to 2.9 ± 1.7), constipation (from 7.5 ± 1.3 to 3.2 ± 2.2), and diarrhea (6.7 ± 2.3 to 2.5 ± 1.9) (p < 0.001). Colicron could be useful in symptom relief, reducing abdominal pain and improving stool consistency of IBS patients. However, further controlled clinical trials are needed to confirm these preliminary findings.

Effectiveness of an amino acid beverage formulation in diarrhea-predominant irritable bowel syndrome: A pragmatic real-world study.

Amino-acid based medical foods have shown promise in alleviating symptoms of drug induced gastrointestinal side effects; particularly, diarrhea-predominant symptoms. Irritable bowel syndrome (IBS) is a gastrointestinal disorder that affects up to 9% of people globally, with diarrhea predominant IBS (IBS-D) being the most prevalent subtype. Further trials are needed to explore potential added benefits when integrated into standard care for IBS-D. To assess the effectiveness of an amino acid-based medical food as an adjunct to standard of care for adults with IBS-D. This is a pragmatic, real world, open label, single arm study comparing a 2-week baseline assessment to a 2-week intervention period. One hundred adults, aged 18 to 65 years, with IBS-D, according to Rome IV criteria, were enrolled after completing a 2-week baseline assessment period and received a 2-week supply of an amino acid based medical food which was consumed at home twice daily on top of their standard of care. The primary outcome was an assessment of tolerability after 2-weeks of consumption, while secondary outcomes included changes in stool consistency (Bristol Stool Form Scale), severity of abdominal pain & discomfort, symptoms of urgency, Global Improvement Survey (GIS), and the IBS severity scoring system (IBS-SSS). The test product was well-tolerated as each participant successfully completed the full 14-day trial, and there were no instances of dropouts or discontinuation of the study product reported. Forty percent of participants achieved a 50% or more reduction in the number of days with type 6-7 bowel movements (IBS-D stool consistency responders). Fifty-three percent of participants achieved a clinically meaningful reduction of 30% in mean weekly pain scores, and 55% experienced the same for mean weekly discomfort scores (IBS-D pain and discomfort responders). Participants experienced a mean -109.4 (95% confidence interval: -130.1, -88.8) point reduction on the IBS-SSS and 52% experienced a minimally clinically important difference of > 95 points. An IBS-SSS category shift from severe to moderate or mild occurred in 69% of participants. For functional symptoms, 76% of participants reported symptom relief on the GIS. The amino acid-based medical food was well-tolerated, when added to the standard of care, and demonstrated improvements in both overall IBS symptom severity and IBS-D symptoms within just 2 wk.

Effect of aged garlic extract on blood pressure and other cardiovascular markers in hypertensive patients and its relationship with dietary intake

ObjectivesThis study evaluates the intake, tolerability and effect of aged garlic extract (AGE) on cardiovascular markers (blood pressure, body composition, glycemic and lipid parameters), stool consistency and its relationship with dietary factors. Casuistry and MethodsThis is a randomized, double-blind, placebo-controlled clinical trial that included 19 hypertensive volunteers. Participants were randomly treated daily with 1.2 g of AGE (1.2 mg of s-allylcysteine) or placebo for 12 weeks. Mixed model analysis was used to detect possible pressure, dietary and body changes, which were assessed every 4 weeks. At these times the consistency of the stool was also evaluated using the Bristol scale. The biological markers, collected before and after the experimental period (fasting glucose, glycated hemoglobin, total cholesterol, low density lipoprotein, high density lipoprotein, very low-density lipoprotein, triglycerides, and non-HDL cholesterol) were analyzed using parametric tests. ResultsOnly the AGE group showed significant reductions in systolic levels at week 4 and 12. This pressure variation was correlated with the average intake of vitamin B12 and B9. An improvement in stool consistency was identified only in the experimental group. Modest reductions in biochemical markers were identified in the AGE group and a significant decrease in glycated hemoglobin occurred in the placebo group. There was no significant difference in dietary and anthropometric variables in the treated groups. ConclusionThe 12-week intervention of 1.2 mg of AGE resulted in a decrease in systolic blood pressure and clinical improvements in stool consistency, glycemic parameters and low-density lipoprotein in hypertensive patients with treated but uncontrolled blood pressure. In addition, we found a correlation between the variation in blood pressure levels and the dietary intake of vitamins B9 and B12 in the group treated with AGE.

Association between Dietary Intake of Live Microbes and Chronic Constipation in Adults

BackgroundChronic constipation (CC) is a common gut health problem, and the role of live dietary microbes in CC is unclear. ObjectiveThis study aimed to investigate the relationship between dietary live microbes consumption and CC. MethodsUsing the National Health and Nutrition Examination Survey data (2005–2010), 11,170 adults who completed the 24-h face-to-face dietary recall and bowel health questionnaire were identified. CC was defined by the Bristol Stool Form Scale. Dietary live microbes intake was classified as low, medium, and high. Additionally, combined medium and high categories (MedHi) were analyzed. Multivariate regression models were constructed to assess the association between dietary intake of live microbes and CC. ResultsIn the weighted sample, the age-adjusted CC prevalence was 7.06% (95% confidence interval [CI]: 6.45, 7.67). In multivariate regression models, after controlling for potential confounders race/ethnicity, sex, body mass index, education, poverty, depression, caffeine intake, and alcohol intake, a significant inverse association between dietary live microbes consumption and CC was observed (odds ratio [OR]: 0.77, 95% CI: 0.61, 0.97, P-trend = 0.061). ConclusionsOur findings suggest that a high dietary live microbes consumption may be associated with lower odds of CC. However, further prospective studies are essential to confirm its effectiveness in reducing CC occurrence.

The structure of gastrointestinal tract pathology in patients receiving hemodialysis treatment

BACKGROUND. Hemodialysis patients are characterized by a wide range of concomitant diseases, including cardiovascular, bone mineral, nutritional, cognitive, various metabolic disorders and anemia. Meanwhile, gastrointestinal tract disorders in these patients remains largely unexplored. Patients receiving treatment with programmed hemodialysis are characterized by a wide range of concomitant diseases, including cardiovascular, bone mineral, nutritional, cognitive, various metabolic disorders and anemia. Meanwhile, the pathology of the gastrointestinal tract in this category of patients remains largely unexplored.AIM: to investigate the structure of digestive diseases in patients receiving hemodialysis treatment.PATIENTS AND METHODS. This study included 180 hemodialysis patients. The median age was 60[47;68] years. Gastrointestinal Symptoms Questionnaire (GSQ) was used to evaluate gastrointestinal symptoms over the last month. The results of abdomen ultrasound, gastroscopy, colonoscopy, and complex laboratory examination were also analyzed.RESULTS. The overall prevalence of gastrointestinal symptoms was 77.2 % (139/180). The most frequent complaints were constipation (46.8 %) and abdominal pain (41 %). The most common stool frequency was one bowel action per day. The third, fourth, fifth type of stool according to the Bristol Stool Form Scale were noted by the majority of participants. Abdominal ultrasound revealed diffuse liver changes in 115 (63.9 %), signs of cirrhosis – in 7(3.9 %) patients. Ultrasound pathology of the gallbladder was represented by anomalies of its shape in 11.1 %, signs of chronic cholecystitis – in 10 %, stones (sludge) – in 7.2 %, polyps – in 2.2 % of patients. Diffuse changes in pancreatic parenchyma, steatosis, pseudocysts and dilatation of the main pancreatic duct were diagnosed respectively in 39(21,7 %), 21(11,7 %), 10(5,6 %) and 3(1.7 %) hemodialysis patients. According to 154 gastroscopies, the most common endoscopic finding in the stomach was chronic gastritis, detected in 86(55.8 %) of the subjects. Erosive gastritis was diagnosed in 22(14.3 %), gastric ulcer – in 3(2.0 %) patients. Endoscopic duodenal pathology was represented by erythematous duodenitis in 53(34.4 %), erosive duodenitis in 15(9.7 %), ulcer in 2(1.3 %), duodenal bulb abnormalities in 23(14.9 %) patients. Combined gastric and duodenal lesions were found in 88(57.1 %) patients. Сolonoscopy was performed in 56 patients, of whom 15 (26.8 %) had signs of colitis (mainly sigmoiditis), 2(3.6 %) – diverticulitis, 10(17.9 %) – diverticulosis, 12(21.4 %) – colon polyps, 8(14.3 %) – angiodysplasia mucosa, in 3(5.4 %) – dolichocolon. Despite the abundance of gastrointestinal symptoms and instrumental findings, no significant deviations in laboratory parameters (including an increase in AST, ALT, total bilirubin, amylase, lipase) were found.CONCLUSION. Hemodialysis patients are characterized by a high prevalence of gastrointestinal symptoms and various pathological changes in the gastrointestinal tract, the diagnosis and treatment of which require an individual multidisciplinary approach.

Abstract PR017: Enabling broad population access to facilitate gut microbiome discoveries

Abstract Microbial associations with colorectal cancer (CRC) are well recognized as well as the potential of using microbiome-based signals for broad-scale, non-invasive screening programs, particularly in underserved communities. Variability within microbiome workflows including sample collection is a contributing factor to inconsistent and non-translatable microbiome results. This limits microbiome discoveries associated with CRC and the development of such screening programs. In addition, ensuring participant and patient adherence can be a challenging prospect with fecal sample collections, and non-adherence (i.e., patient dropout, collection errors) can increasingly strain resources. An intuitively designed sample collection device should increase adherence across the general population while minimizing failed collections. Enabling the at-home collection of gut microbiome samples removes barriers between patients and testing while providing the scalability and flexibility needed for large studies or screening programs. Across two studies, 152 naïve participants were recruited to evaluate comprehension of and adherence to the OMNIgene™•GUT Dx device Instructions for Use (IFU). Both studies were designed with key considerations related to user group selection, sample size, population demographics, education level, and relevant real-world scenarios. In the first study (n=118), each participant was observed collecting one simulated “fecal” sample with representation across the Bristol scale (Type 1 to 7). The study observer conducted a follow-up interview with the participant regarding incorrect actions during collection. In the second study (n=34), participants collected one real fecal sample at home and returned it to the laboratory using standard postal services. Samples were inspected at the laboratory for collection adherence with the IFU by evaluating device closure, sufficient mixing, and DNA yield. DNA was extracted using the QIAamp PowerFecal Pro kit (QIAGEN) and quantified using PicoGreen (Invitrogen). In both studies, participants were asked to complete comprehension questionnaires to test understanding of the IFU used during collection. Participants demonstrated high rates of comprehension by answering the questions correctly 94% of the time. Participants observed collecting simulated samples demonstrated success rates of 87% for all tasks overall. Samples evaluated from the second study demonstrated participant adherence where 100% of samples were correctly returned via standard postal systems supporting at-home direct-to-consumer settings; 100% of participants properly closed the tube ensuring no loss of sample during transport; 97% of participants adequately mixed the sample; and 97% of participant samples provided sufficient DNA (≥ 120 ng) per extraction aliquot for downstream analysis. Results from these usability studies demonstrate that the OMNIgene™•GUT Dx device provides an easy-to-use at-home collection solution for diverse populations, especially at-risk, minority populations without easy access to clinical services. Citation Format: Ashlee Brown, Savannah Colameco, Tara Crawford Parks. Enabling broad population access to facilitate gut microbiome discoveries [abstract]. In: Proceedings of the 16th AACR Conference on the Science of Cancer Health Disparities in Racial/Ethnic Minorities and the Medically Underserved; 2023 Sep 29-Oct 2;Orlando, FL. Philadelphia (PA): AACR; Cancer Epidemiol Biomarkers Prev 2023;32(12 Suppl):Abstract nr PR017.

Characteristics of functional constipation and the need for treatment with traditional medicine of students in University of Medicine and Pharmacy, Hue University

Background: Functional constipation (FC) is considered as a common functional bowel disorder that have substantial impact on patient quality of life. Objectives: To study characteristics of FC and the need for treatment with traditional medicine of students in University of Medicine and Pharmacy, Hue University. Materials and method: A cross-sectional descriptive study was conducted in 451 students from 9 academic majors at University of Medicine and Pharmacy, Hue University. Using the Bristol Stool Form (BSF) Scale to characterize human stool and ROME III Diagnostic Questionnaire to assess constipation symptoms, using anxiety, depression, stress rating scale - DASS-21. Results: The prevalence of FC among students was 8.9% (40/451) according to ROME III criteria, female are higher than male (85.0% vs 15.0%). According to traditional medicine, Deficiency accounts for 65.0%, Excess 60.0%, Cold 42.5% and Heat 57.5%. Qi stagnation pattern accounts for 42.5%, Qi deficiency pattern 25.0%, large intestinal heat bind pattern 20.0%, blood deficiency pattern 10.0% and yang deficiency pattern 2.5%. The proportion of students who need for treatment with traditional medicine is 52.5%, acupress massage and traditional medicines are the two methods with the highest demand for treatment. Conclusion: FC among students in University of Medicine and Pharmacy, Hue University are with relatively high prevalence. Most of them have manifestations of Excess and Deficiency, Qi stagnation pattern and Qi deficiency pattern are higher than the other. Demand for treatment of FC with traditional medicine is quite high, most of them need treatment with acupress massage and traditional medicines. Key words: functional constipation, students, the need for treatment, ROME III criteria.

Gut microbial composition mediates the relationship between intestinal inflammation and amyloid burden before cognitive decline

AbstractBackgroundGut microbial composition is associated with Alzheimer’s disease (AD) pathology, and recent findings (Heston et al, medRxiv 2022) have identified an increase in intestinal inflammation with greater age and with higher cortical amyloid burden. Although gut microbiome composition and intestinal inflammation have independently been linked to AD pathology, it remains unclear whether the microbiome and gut inflammation are interrelated in the context of preclinical AD. Here we used phylogenetically‐based mediation (PhyloMed) to test whether the gut microbiome mediates the relationship between gut inflammation and cortical amyloid burden, and to highlight bacterial clades that may be specifically implicated as mediators.Method78 participants (Table 1) were enrolled in the Wisconsin Alzheimer’s Disease Research Center and Wisconsin Registry for Alzheimer’s Prevention, collected fecal samples, and completed C11‐PiB PET. Figure 1 illustrates the processing and analysis for each data stream. Fecal calprotectin was measured to quantify intestinal inflammation, and 16S rRNA sequencing characterized the fecal microbiome. Testing the full cohort and the cognitively unimpaired (CU) subset separately (n = 73), PhyloMed was performed at every taxonomic level, resulting in 14 models. Covariates included age, sex, body mass index, Bristol Stool Scale score, cognitive diagnosis/amyloid status, pseudocontinuous APOE AD risk score, and age difference between PET scan and fecal sample.ResultFor both the full and CU cohorts, models at the amplicon sequence variant (ASV) level showed that gut microbiome composition was a significant mediator (p&lt;0.05); species‐ and genus‐level models were marginally significant (p&lt;0.1, Benjamini‐Hochberg FDR) (Table 2). ASVs from the family Lachnospiraceae (Figure 2A) were highlighted as significantly mediating taxa (p&lt;.05, FDR). Interestingly, these taxa were negatively associated with calprotectin, while they were positively associated with PiB DVR (Figures 2B, 2C).ConclusionEven before cognitive decline, the gut microbiome mediated the relationship between calprotectin, a measure of gut inflammation, and cortical PiB DVR, a measure of amyloid burden. Taxa within Lachnospiraceae were implicated as specific mediators, linked with lower inflammation and higher amyloid burden. Future work will use germ‐free mouse models to functionally elucidate the role of these bacteria in inflammation and AD.

Gut microbial composition mediates the relationship between intestinal inflammation and amyloid burden before cognitive decline

AbstractBackgroundGut microbial composition is associated with Alzheimer’s disease (AD) pathology, and recent findings (Heston et al, medRxiv 2022) have identified an increase in intestinal inflammation with greater age and with higher cortical amyloid burden. Although gut microbiome composition and intestinal inflammation have independently been linked to AD pathology, it remains unclear whether the microbiome and gut inflammation are interrelated in the context of preclinical AD. Here we used phylogenetically‐based mediation (PhyloMed) to test whether the gut microbiome mediates the relationship between gut inflammation and cortical amyloid burden, and to highlight bacterial clades that may be specifically implicated as mediators.Method78 participants (Table 1) were enrolled in the Wisconsin Alzheimer’s Disease Research Center and Wisconsin Registry for Alzheimer’s Prevention, collected fecal samples, and completed C11‐PiB PET. Figure 1 illustrates the processing and analysis for each data stream. Fecal calprotectin was measured to quantify intestinal inflammation, and 16S rRNA sequencing characterized the fecal microbiome. Testing the full cohort and the cognitively unimpaired (CU) subset separately (n = 73), PhyloMed was performed at every taxonomic level, resulting in 14 models. Covariates included age, sex, body mass index, Bristol Stool Scale score, cognitive diagnosis/amyloid status, pseudocontinuous APOE AD risk score, and age difference between PET scan and fecal sample.ResultFor both the full and CU cohorts, models at the amplicon sequence variant (ASV) level showed that gut microbiome composition was a significant mediator (p&lt;0.05); species‐ and genus‐level models were marginally significant (p&lt;0.1, Benjamini‐Hochberg FDR) (Table 2). ASVs from the family Lachnospiraceae (Figure 2A) were highlighted as significantly mediating taxa (p&lt;.05, FDR). Interestingly, these taxa were negatively associated with calprotectin, while they were positively associated with PiB DVR (Figures 2B, 2C).ConclusionEven before cognitive decline, the gut microbiome mediated the relationship between calprotectin, a measure of gut inflammation, and cortical PiB DVR, a measure of amyloid burden. Taxa within Lachnospiraceae were implicated as specific mediators, linked with lower inflammation and higher amyloid burden. Future work will use germ‐free mouse models to functionally elucidate the role of these bacteria in inflammation and AD.

Patient Recorded Outcomes from a Randomized, Controlled Phase 2 Trial of E-Selectin Inhibition with Uproleselan Vs Placebo to Reduce GI Toxicity during Melphalan-Conditioned Autologous Hematopoietic Cell Transplantation for Multiple Myeloma

Background: The use of high-dose melphalan conditioning followed by autologous hematopoietic cell transplant (AHCT) continues to be a key component in the treatment of patients with multiple myeloma (MM). However, high-dose melphalan is associated with a high rate of GI toxicity (&amp;gt;90%), which adversely impacts clinical outcomes and negatively influences patient quality of life (QoL). Indeed, it has been reported that AHCT leads to short-term deterioration of health-related QoL in patients with MM, and QoL typically improves by 2-3 months post-AHCT. Pre-clinical and clinical data suggest that E-selectin inhibition may play a role in reducing immune-mediated GI epithelial injury following cytotoxic chemotherapy. We hypothesized that uproleselan (upro), a synthetic, competitive E-selectin antagonist, may improve health-related QoL by reducing risk of chemotherapy-induced diarrhea in patients undergoing AHCT. Methods: We conducted a Phase 2, single-center, randomized, double-blind, placebo-controlled trial in patients with MM receiving high-dose melphalan (200 mg/m2) as conditioning for AHCT for MM. Patients were randomized 1:1 to receive prophylactic upro+standard of care (SoC) vs placebo+SoC. Uproleselan was given in 6 doses of 800 mg IV starting on day-3 through day 0. The primary endpoint was diarrhea severity as assessed by CTCAE v5.0 (secondary endpoint - Bristol Stool Scale). In addition, a key secondary endpoint was patient reported outcomes (PRO) of GI-related QoL using the National Cancer Institute (NCI) PRO-CTCAE Measurement System, a validated PRO tool developed to evaluate symptomatic toxicities in patients with cancer in clinical trials. Significance level of p&amp;lt;0.2 was pre-specified for all endpoints, per protocol. Patients were surveyed during the peri-transplant period at day-3 (baseline), day+8, and day+14 or day of discharge (DoD). Responses were graded on a scale of 1-5, with 1 indicating absence of symptoms or zero interference with daily activities and 5 indicating very severe symptoms or very significant interference with daily activities. GI-specific domains assessed included swallowing, mouth sores, appetite, nausea, vomiting, heartburn, bloating, abdominal pain, flatulence, and incontinence. Results: Fifty adult patients with MM were enrolled from 5/2021-10/2022. Baseline PRO symptoms were similar between the upro+SoC and placebo+SoC arms at baseline (day-3). By day+8 post-AHCT patients in the upro+SoC arm reported a significant improvement in severity of GI-related symptoms across 30% (6/20) of domains surveyed vs placebo+SoC (p=0.07-0.14). Furthermore, improvement in mouth sore-related symptoms continued to day+14 post-AHCT in the upro+SoC arm vs placebo+SoC (p=0.17). The remaining GI-related symptoms returned to baseline by D+14 or DoD (p&amp;gt;0.20). Also of note, a numerically lower mean diarrhea severity score and lower incidence of Grade 3 diarrhea (by CTCAE v5.0) was observed favoring upro+SOC which did not meet the pre-specified significance threshold (p=0.34, p=0.26, respectively). However, a significant reduction in severe diarrhea (by Bristol Stool Scale) was observed favoring upro+SoC (p=0.10) vs placebo+SoC, with improvement in the upro+SoC arm to mild diarrhea (p=0.02). Conclusions: Upro+SoC resulted in a clinically significant improvement in GI-toxicity related symptoms as assessed via PRO-CTCAE in patients with MM undergoing melphalan-conditioned AHCT, when compared to placebo+SoC. These improvements in patient reported outcomes are further supported by data from the primary and additional secondary endpoints of the study. Taken together, these results suggest prophylactic E-selectin inhibition may represent a promising strategy to mitigate chemotherapy-associated GI-toxicity. Further studies are needed to verify these findings and to further define the optimal dosing of upro in the peri-AHCT period.

Xylo-oligosaccharides improve functional constipation by targeted enrichment of Bifidobacterium.

Functional constipation (FC) has a negative impact on patients' quality of life. We hypothesized that dietary supplementation with xylo-oligosaccharides (XOS) or fructo-oligosaccharides (FOS) would improve constipation symptoms by influencing the gut microbiota. A randomized double-blind controlled trial was conducted in FC patients. Patients were randomly divided into 6 groups and given a dietary supplement containing XOS at doses of 3, 5, or 10 g/day, FOS at doses of 10 and 20 g/day, or placebo at 5 g/day for one month. We compared improvements in gastrointestinal function after the intervention using the Bristol Stool Form Scale (BSFS), Cleveland Clinic Constipation Score (CCCS), and Quality of Life Scale for Patients with Constipation (PAC-QoL). 16S rRNA sequencing was used to assess changes in the structure of the gut microbiota. Changes in individual bacteria had significant effects in reducing gastrointestinal symptoms during the intervention, even though the flora structure remained unchanged from baseline. Compared to FOS, XOS enriched Bifidobacterium at a lower dose, and patients receiving XOS supplementation showed significant improvements in constipation symptoms without side effects such as diarrhea and flatulence.

Evaluation of the Efficacy of Kombucha-Based Drink Enriched with Inulin and Vitamins for the Management of Constipation-Predominant Irritable Bowel Syndrome in Females: A Randomized Pilot Study

BackgroundConstipation-predominant irritable bowel syndrome (IBS-C) mainly affects females, and dietary interventions for symptom relief often yield poor results because of low patient adherence. The development of functional food products enriched with dietary fibers may increase patients’ adherence to a healthy diet and relieve IBS-С symptoms. ObjectiveThis proof-of-concept, open-label, randomized controlled pilot study is aimed to evaluate the efficacy of kombucha enriched with inulin and vitamins in females with IBS-C. MethodsForty females with IBS-C were randomly assigned to receive either 220 mL of kombucha enriched with inulin (2.53 g/220 mL) and vitamins (B1 – 0.59 mg, B2 – 0.55 mg, B3 – 5.9 mg, B6 – 0.7 mg, and folic acid – 81.4 μg/220 mL) or water for 10 d. Stool frequency, Bristol stool scale score (BSSS), and abdominal symptoms were evaluated using a 5-point Likert scale on days 5, 9 and 14 of the study. The palatability of the drink was assessed using a visual analog scale. ResultsAfter 10 d, the kombucha group showed a significant increase in stool frequency (0.60 ± 0.31–0.85 ± 0.19 times/d; P = 0.004) compared with the control (0.63 ± 0.33 compared with 0.72 ± 0.28; P = 0.6). The mean values of the BSSS increased in the kombucha group (3.0 ± 1.2–4.4 ± 1.0; P = 0.001), whereas they remained unchanged in the control (2.9 ± 1.2 compared with 3.4 ± 1.2; P = 0.6). The kombucha group also experienced a significant decrease in the feeling of incomplete bowel emptying (1.88 ± 0.78 compared with 1.41 ± 0.56 points; P = 0.015), which was not observed in the control group. ConclusionsShort-term consumption of kombucha enriched with inulin and vitamins was associated with an increase in stool frequency, an improvement in the BSSS, and a reduction in the feeling of incomplete bowel emptying in females with IBS-C. Further large-scale clinical trials investigating the efficacy of kombucha enriched with inulin and vitamins in patients with IBS-C are warranted to prove the observed effects. Trial registration numberThis trial was registered at clinicaltrials.gov as NCT05164861 (==https://clinicaltrials.gov/study/NCT05164861?term=NCT05164861&rank=1; registered on 18 December, 2021).

Effectiveness of L-serine supplementation in children with a GRIN2B loss-of-function mutation: Rationale and protocol for single patient (n-of-1) multiple cross-over trials

RationaleLoss-of-function (LoF) mutations in GRIN2B result in neurologic abnormalities due to N-methyl-D-aspartate receptor (NMDAR) dysfunction. Affected persons present with various symptoms, including intellectual developmental disability (IDD), hypotonia, communication deficits, motor impairment, complex behavior, seizures, sleep disorders and gastrointestinal disturbance. Recently, in vitro experiments showed that D-serine mitigates function to GluN2B (mutation)-containing NMDARs. 11 previous case reports are published on (experimental) L-serine treatment of patients between 1.5 and 12 years old with GRIN2B missense or null mutations, some of whom showed notable improvement in motor and cognitive performance, communication, behavior and abnormalities on electro encephalography (EEG). Our objective is to further evaluate the effectiveness of L-serine for GRIN2B-related neurodevelopmental disorder (GRIN2B-NDD), using an n-of-1 trial design, increasing the level of evidence. Methods/designThese n-of-1 trials, consisting of 2 cycles of 6 months, will be performed to evaluate the effect of L-serine compared to placebo in 4 patients with a GRIN2B LoF mutation. The aggregation of multiple n-of-1 trials will provide an estimate of the average treatment effects.The primary outcome is the Perceive-Recall-Plan-Perform of Task Analysis, assessing developmental skills. Secondary outcomes include Goal Attainment Scaling, seizure log books, EEGs, sleep log books, the irritability subscale of the Aberrant Behavior Checklist, the Bristol Stool Scale and the Pediatric Quality of Life Inventory. ConclusionThis study employs an innovative methodological approach to evaluate the effectiveness of L-serine for patients with a GRIN2B LoF mutation. The results will establish a foundation for implementing L-serine as a disease-modifying treatment in GRIN2B-NDD.

Association between frailty and chronic constipation and chronic diarrhea among American older adults: National Health and Nutrition Examination Survey

BackgroundThis study was to explore the relationship between chronic constipation, chronic diarrhea, and frailty in older Americans.MethodsThis cross-sectional study selected a total of 4241 community-dwelling individuals aged 60 years and older from the 2005–2010 National Health and Nutrition Examination Survey. Frailty was measured using a 49-item frailty index, and a frailty index > 0.21 was defined as a frail status. Chronic constipation and chronic diarrhea were defined as the “usual or most common type of stool” by the Bristol Stool Form Scale (BSFS) Types 1 and 2 and BSFS Types 6 and 7, respectively. Weighted logistic regression analysis was used to examine the relationship between gut health and frailty status. Restricted cubic spline (RCS) curves were built to assess the association between frailty index and stool frequency.ResultsFrailty status was associated with higher odds of constipation in an unadjusted model; however, after further adjusting for confounding variables, the relationship between frailty status and constipation was not statistically significant. We discovered a positive correlation between the frailty status and diarrhea after adjustment for all variables. The frailty index showed a U-shaped relationship with stool frequency, and the frailty index was the smallest at a frequency of 10 stools/week.ConclusionNegative associations were observed between frailty status and chronic constipation and diarrhea among older adults. Older adults who have a bowel movement frequency of about 10 times per week are the least frail. Future studies are warranted to confirm the causal relationship in this association.

The incidence of chronic diarrhea decreases with increasing serum calcium levels: a cross-sectional study based on NHANES 2005–2010

BackgroundChronic diarrhea is difficult to prevent and treat due to its complex etiology and pathogenesis. It places a huge burden on patients and public healthcare. It is known that the regulation of body homeostasis relies heavily on calcium. However, in the general population, the relationship between calcium and chronic diarrhea remains uncertain.MethodsWe assessed the association between serum calcium and diarrhea using data from the 2005–2010 National Health and Nutrition Examination Survey (NHANES). Serum calcium level was measured from collected blood samples. Diarrhea was assessed using the Bristol Stool Scale (BSFS) (types 1–7). The stability of the results was assessed using logistic regression and sensitivity analysis. The dose–response association between serum calcium and the risk of diarrhea was analyzed using a restricted cubic spline plot.ResultsThis study included 12,342 participants. In each of the five models, an increased calcium level was negatively associated with the incidence of diarrhea (OR[95%CI]:0.26 [0.13–0.53], 0.28 [0.14–0.58], 0.4 [0.19–0.82], 0.27 [0.11–0.64] and 0.24 [0.10–0.59], respectively). When serum calcium was analyzed as a categorical variable, a significant association between serum calcium and diarrhea prevalence was found. The restricted cubic spline plot showed a linear relationship between serum calcium and diarrhea. Sensitivity analysis confirmed that the results were stable.ConclusionThe results of our cross-sectional study suggest that a higher level of serum calcium may reduce the incidence of diarrhea. In the future, this finding should be further validated in a randomized controlled trial.