Stool Consistency Score Research Articles

Characterization of idiopathic chronic diarrhea and associated intestinal inflammation and preliminary observations of effects of vagal nerve stimulation in a non-human primate.

Diarrhea is commonly associated with irritable bowel syndrome, inflammatory bowel disease, microscopic colitis, and other gastrointestinal dysfunctions. Spontaneously occurring idiopathic chronic diarrhea is frequent in rhesus macaques, but has not been used as a model for the investigation of diarrhea or its treatment. We characterized this condition and present preliminary data demonstrating that left vagal nerve stimulation provides relief. Stool consistency scores were followed for up to 12 years. Inflammation was assessed by plasma C-reactive protein, [18F]fluorodeoxyglucose (FDG) uptake, measured by positron emission tomography (PET), multiplex T cell localization, endoscopy and histology. The vagus was stimulated for 9 weeks in conscious macaques, using fully implanted electrodes, under wireless control. Macaques exhibited recurrent periods of diarrhea for up to 12 years, and signs of inflammation: elevated plasma C-reactive protein, increased bowel FDG uptake and increased mucosal T helper1 T-cells. The colon and distal ileum were endoscopically normal, and histology revealed mild colonic inflammation. Application of vagal nerve stimulation to conscious macaques (10 Hz, 30 s every 3 h; 24 h a day for 9 weeks) significantly reduced severity of diarrhea and also reduced inflammation, as measured by FDG uptake and C-reactive protein. These macaques exhibit spontaneously occurring diarrhea with intestinal inflammation that can be reduced by VNS. The data demonstrate the utility of this naturally occurring primate model to study the physiology and treatments for chronic diarrhea and the neural control circuits influencing diarrhea and inflammation that are not accessible in human subjects.

A case-control study of the risk factors for fistula-in-ano in infants and toddlers

BackgroundLimited data are available regarding the risk factors for fistula-in-ano (FIA) in infants and toddlers, potentially affecting their daily lives.ObjectivesThe purpose of this study was to identify potential risk factors for FIA in infants and toddlers, in order to implement early preventive interventions, avoid disease progression, and develop therapeutic strategies.Design and settingsA retrospective case-control study was conducted, comparing 41 infants and toddlers diagnosed with FIA with 41 healthy controls, between August 2020 and December 2021.Independent variables(a) maternal characteristics during pregnancy and delivery, (b) perinatal characteristics, dietary behaviors, and defecation-related behaviors in infants and toddlers, (c) family dietary behaviors.ResultsMothers of infants and toddlers with FIA had given birth more times in the past, while the infants and toddlers themselves had less mealtime, a higher rate of exclusive breastfeeding, frequent loose stools, and a larger proportion of used wipes, experiencing perianal skin anomalies. The logistic regression analysis revealed that there are four significant risk factors associated with the development of FIA in infants and toddlers, including the number of previous deliveries by the mother (OR 6.327), defecation frequency score (OR 5.351), stool consistency score (OR 5.017), and cleaning with wipes after defecation (OR 8.089).ConclusionBased on our data, it appeared that FIA in infants and toddlers could be attributed to several factors. These included an increased number of previous deliveries by mothers, frequent loose stools, and repeated wipe use. To prevent the occurrence and worsening of the disease, it is important to improve the frequency and consistency of stooling and provide proper care. Further research is required to verify these findings in other clinical settings.

Long-Term Tracking of the Effects of Colostrum-Derived Lacticaseibacillus rhamnosus Probio-M9 on Gut Microbiota in Mice with Colitis-Associated Tumorigenesis.

Intestinal bacteria play important roles in the progression of colitis-associated carcinogenesis. Colostrum-derived Lacticaseibacillus rhamnosus Probio-M9 (Probio-M9) has shown a protective effect in a colitis-associated cancer (CAC) model, but detailed metagenomic analysis had not been performed. Here, we investigated the preventive effects of the probiotic Probio-M9 on CAC-model mice, tracking the microbiota. Feces were obtained at four time points for evaluation of gut microbiota. The effect of Probio-M9 on tight junction protein expression was evaluated in co-cultured Caco-2 cells. Probio-M9 treatment decreased the number of tumors as well as stool consistency score, spleen weight, inflammatory score, and macrophage expression in the CAC model. Probio-M9 accelerated the recovery of the structure, composition, and function of the intestinal microbiota destroyed by azoxymethane (AOM)/dextran sulfate sodium (DSS) by regulating key bacteria (including Lactobacillus murinus, Muribaculaceae bacterium DSM 103720, Muribaculum intestinale, and Lachnospiraceae bacterium A4) and pathways from immediately after administration until the end of the experiment. Probio-M9 co-culture protected against lipopolysaccharide-induced impairment of tight junctions in Caco-2 cells. This study provides valuable insight into the role of Probio-M9 in correcting gut microbiota defects associated with inflammatory bowel disease carcinogenesis and may have clinical application in the treatment of inflammatory carcinogenesis.

A187 PROPHYLACTIC PHAGE TREATMENT ENHANCES SUB-THERAPEUTIC EFFICACY OF BUDESONIDE AGAINST E. COLI DRIVEN COLITIS IN MICE COLONIZED WITH A DEFINED MICROBIOTA

Abstract Background Patients with IBD are increasingly experiencing treatment failures on frontline therapies. While corticosteroids are an effective frontline intervention, 16% of patients fail to respond, and 20%–30% show only partial responses. Bacteriophages have recently garnered attention as a potential adjunctive therapy for IBD to target bacterial strains associated with IBD, including adherent-invasive Escherichia coli (AIEC). Aims Our aim was to determine whether prophylactic bacteriophage therapy could enhance the therapeutic efficacy of a sub-therapeutic dose of budesonide in a gnotobiotic mouse model of E. coli-driven colitis. Methods Adult germ-free C57BL/6 mice were co-colonized with altered Schaedler-like flora (ASF) plus E. coli NRG857c, a Crohn’s disease-associated bacterial isolate. Three weeks later, mice were treated with phage HER259 (1x109 PFU/dose; 0.1% bicarbonate) 3 times/ week or vehicle (PBS with 0.1% bicarbonate) 3 times/ week (n=5/group). Mice were then exposed to low-dose dextran sulfate sodium (2%; DSS) in drinking water for 5 days, followed by 2 days of water. All mice were administered a subtherapeutic dosage of 2ug/day of Budesonide halfway through DSS exposure to endpoint. Mice were monitored daily for weight loss, stool consistency, and fecal occult blood. At sacrifice, colon tissue was collected for histological analysis. Results Compared with budesonide treatment alone, prophylactic phage treatment, followed by a sub-therapeutic dose of budesonide, led to reduced stool consistency scores (p ampersand:003C0.001) and reduced presence of occult blood (p ampersand:003C 0.001). No difference in fecal E. coli load was observed between groups. At endpoint, the combined phage-budesonide treatment was associated with lower histological scores as compared with mice treated with budesonide alone (p ampersand:003C 0.01). Conclusions While underlying mechanisms remain elusive, our results suggest a beneficial effect of prophylactic phage intervention to the subsequent administration of a frontline immunosuppressive compound used to treat IBD. Future work will investigate the mechanisms by which adjunctive phage therapy can enhance existing therapies used to treats colitis, to better inform clinical guidelines. Funding Agencies CIHR

A NEW APPROACH FOR TREATMENT OF ULCERATIVE COLITIS: A MELANOCORTIN RECEPTOR AGONIST PL8177

Abstract INTRODUCTION The melanocortin system plays an important role in resolving inflammatory processes. The melanocortin 1 receptor (MC1R)–specific agonist PL8177 has demonstrated MC1R binding affinity and functional activity that mirrors that of α-melanocyte–stimulating hormone. The effect of PL8177 on inflammation, cell population composition, and gene and protein expression was investigated in colons from a dextran sulfate sodium (DSS)–induced rat model of colitis. METHODS Colitis was induced by 5% DSS in drinking water. Rats received vehicle control (placebo) capsules, oral PL8177 capsules (20, 50, and 100 μg per animal), or mesalazine (positive control). Colons were harvested on day 8. Samples were analyzed for cytokines, and by single nuclei RNA-seq and data-independent acquisition tandem mass spectrometry phosphoproteome profiling. Colitis was assessed by diarrhea and rectal bleeding, colon length shortening, colon weight gain, and histopathology. Total colitis index assessed inflammatory damage. RESULTS PL8177 50 μg showed a significant (P<0.05) improvement in colon weight (53% reduction), stool consistency, and fecal occult blood score vs vehicle, and there was significant improvement in the total colitis index for the PL8177 100-μg group vs vehicle. All PL8177 cohorts showed greater improvement in the total colitis index than mesalazine. Mesalazine produced a marked reduction in colon length, but only moderate improvement (35%) in colon weight. Single nuclei RNA-seq showed that in the PL8177 100-μg group, relative cell populations and key gene expression levels were closer to those of healthy controls PL8177 100-μg treatment caused a relative decrease in immune cells and an increase in enterocytes and enteric glial cells compared to vehicle control. Subclustering analysis revealed significant differences between PL8177 100-μg and vehicle populations. Although both showed the presence of macrophages, vehicle-treated colons were primarily M1 macrophages involved in inflammation. In PL8177 100 μg–treated colons, macrophages were primarily pro-resolution M2. Proteomic analysis showed that PL8177-treated colons are more similar to sham colons than to vehicle colons. Also after treatment with PL8177, Smad 2 and 3, proteins known to promote intestinal homeostasis showed expression similar to that seen in the sham group, a result not seen in vehicle-treated colons. DISCUSSION Oral PL8177 treatment showed significant improvement in anatomical markers of colitis vs the vehicle and mesalazine control groups, supporting the aim of treating inflammatory bowel disease (IBD). Transcriptomics and proteomics data show that oral PL8177 treatment causes diseased colons to move toward the healthy state and to resolve inflammation. Resolving inflammation—rather than blocking it—provides the possibility of efficacy coupled with safety in treating IBD.

Huang Lian Jie Du decoction attenuated colitis via suppressing the macrophage Csf1r/Src pathway and modulating gut microbiota.

Ulcerative colitis, a subtype of chronic inflammatory bowel disease (IBD), is characterized by relapsing colonic inflammation and ulcers. The traditional Chinese herbal formulation Huang Lian Jie Du (HLJD) decoction is used clinically to treat diarrhea and colitis. However, the mechanisms associated with the effects of treatment remain unclear. This study aims to elucidate the molecular mechanistic effects of HLJD formulation on colitis. Chronic colitis in mice was induced by adding 1% dextran sulfate sodium (DSS) to their drinking water continuously for 8 weeks, and HLJD decoction at the doses of 2 and 4 g/kg was administered orally to mice daily from the second week until experimental endpoint. Stool consistency scores, blood stool scores, and body weights were recorded weekly. Disease activity index (DAI) was determined before necropsy, where colon tissues were collected for biochemical analyses. In addition, the fecal microbiome of treated mice was characterized using 16S rRNA amplicon sequencing. HLJD decoction at doses of 2 and 4 g/kg relieved DSS-induced chronic colitis in mice by suppressing inflammation through compromised macrophage activity in colonic tissues associated with the colony-stimulating factor 1 receptor (Csf1r)/Src pathway. Furthermore, the HLJD formula could modify the gut microbiota profile by decreasing the abundance of Bacteroides, Odoribacter, Clostridium_sensu_stricto_1, and Parasutterella. In addition, close correlations between DAI, colon length, spleen weight, and gut microbiota were identified. Our findings revealed that the HLJD formula attenuated DSS-induced chronic colitis by reducing inflammation via Csf1r/Src-mediated macrophage infiltration, as well as modulating the gut microbiota profile.

Blocking the Apelin Receptor (APJ) Attenuates TNBS-Induced Colitis in Rats

Objective: The apelinergic system, consisting of apelin, ELABELA, and the apelin receptor (APJ), has a wide range of roles in physiological and pathophysiological processes in tissues. The effects of increased apelin and APJ as an indicator of damage in inflammatory conditions or as a compensatory mechanism are not fully clear in inflammatory bowel disease (IBD). This study was designed to assess the role of APJ in 2,4,6-trinitrobenzene sulfonic acid (TNBS)-induced colitis model. Methods: Colitis in adult male Wistar rats were induced by intrarectally administered TNBS (30 mg b.w. in 50% ethanol). While the control group was treated with only saline to the colon, the TNBS+F13A and F13A groups received the APJ antagonist F13A (30 µg/kg/day, i.v.) for 3 days, starting immediately after TNBS or saline administration, respectively. Results: A decrease in body weight and an increase in colon weight/length ratio and stool consistency score were observed in the TNBS group. TNBS caused an increase in the myeloperoxidase (MPO) activity and the number of proinflammatory cytokines (TNF-α, IL-1β, and IL-6), as well as apelin production, leading to mucosal ulceration, necrosis, and submucosal edema in the colon. While F13A administration to the control did not cause any change in the colon, F13A administration immediately after TNBS greatly reduced the effects of TNBS. Conclusion: APJ is involved in the development of damage in colitis induced by TNBS. F13A reduces the level of damage, inflammatory cell infiltration, and MPO enzyme activity. APJ may be a therapeutic target in IBD.

Gastrointestinal Tolerability and Acute Glycemic Response of Oligosaccharides and Polysaccharides from Cellulose and Xylan in Healthy Adults: Two Double-Blinded, Randomized, Controlled, Cross-over Trials

Objective The aim of this study was to investigate the gastrointestinal tolerability, glycemic and insulinemic responses of Plant Fiber Extract (PFE), a mixture comprising of oligosaccharides and polysaccharides derived from cellulose and xylan. Methods Two double-blind, randomized, controlled, cross-over trials were conducted in healthy adults. In the first trial, participants (n = 29) consumed either 25, 35 or 45 g per day of PFE or resistant maltodextrin (Control) for 14 days. The occurrence and severity of gastrointestinal (GI) symptoms, stool parameters, and safety outcomes were evaluated with a combination of surveys and blood analysis respectively. In the second trial (n = 20), the post-prandial glycemic and insulinemic responses after the ingestion of 20 g of PFE diluted in water or incorporated into chocolate chips was measured and then compared to that of glucose and regular chocolate, respectively. Results For all timepoints (0, 7 and 14 days), within any given dose group, there was no statistically significant difference in the GI symptoms score between PFE and Control. Further, for each test product (PFE or Control), no difference was observed in the same dose group from days 0 and 14. Stool consistency score and number of participants experiencing loose or watery stools was similar between products. No serious adverse events were reported and neither PFE nor Control significantly altered blood or urine safety parameters. The glycemic and insulinemic responses after PFE ingestion in comparison to glucose were 12% and 8% respectively. The glycemic and insulinemic responses after consuming chocolate containing PFE were 20% of that of regular chocolate. Conclusion PFE was well-tolerated by healthy volunteers in doses up to 45 g/day and it elicited comparatively low glycemic and insulinemic responses when consumed alone or when incorporated into a food product.

Oral iron supplementation exacerbates dextran sulfate sodium (DSS)-induced colitis in mice

Background: Ulcerative colitis (UC) is a chronic inflammatory bowel disease (IBD) characterized by diarrhea, abdominal pain, and bloody, mucous-laden stools. In one-third of UC patients, severity of blood loss is sufficient to cause iron deficiency anemia, making it the most common extra-intestinal manifestation of UC. Oral iron supplementation is the first line treatment for IDA. However, there is a debate concerning the safety of orally administered iron, as some studies have reported an exacerbation of disease, whereas others report the treatment is well tolerated and effective. Aim: The purpose of this study was to determine the effect of oral iron administration on disease activity in dextran sulfate sodium (DSS)-induced colitis in mice, a model that effectively recapitulates ulcerative colitis. Hypothesis: We hypothesize that iron-supplemented chow will increase disease activity and lead to pathogenic changes in mice with DSS-induced colitis. Methods: Experimental acute colitis (UC) was produced in BALBc/AnNCrl (male and female; 7 weeks old) mice by administration of 3% DSS dissolved in drinking water for 7 days. Control mice received standard water. Normal control (NC) and UC (UC) animals were fed standard chow contained 200 parts per million (ppm) ferrous sulfate (2018 Teklad Global 18% Protein Rodent Diet, Huntingdon, UK), while normal (NCFe) and UC (UCFe) experimental animals were fed an iron-supplemented diet containing 600 ppm ferrous sulfate (2018 Teklad Global 18% Protein Rodent Custom Diet, Huntingdon, UK). Food and water were provided ad libitum. Daily scores for weight loss, stool consistency, and fecal blood content were averaged to produce a disease activity index as previously described by Friedman and co-workers (DAI, 2009). On day-8 post-treatment, mice were euthanized with 5% isoflurane. Length of colon was measured from cecum to rectum, and epithelial cells were isolated from distal colon by EDTA chelation technique. Histopathology, RNA isolation, and qRT-PCR analyses were performed using standard techniques. Results: Food and water consumption were not significantly altered among the 4 groups of mice. Additional iron supplementation significantly: 1) increased DAI; 2) decreased fecal dry weight; and 3) increased blood inflammatory cytokine levels in UCFe as compared to UC group. Colon length was shortened one-third in UC as compared to NC, but was not further significantly altered by iron supplementation. Loss of crypt architecture and increased influx of inflammatory cells identified in UC colon was not significantly altered in colons from the UCFe group. Expression of apical iron importer DMT1 was increased in UC as compared to NC, but not in the UCFe group. In total, there were no differences due to iron supplementation, and no differences were present due to gender. Conclusion: We conclude that iron supplementation increases the severity of colitis by stimulating water secretion. This study was supported by the National Institute of Health NIDDK DK104791 and DK112085 grants This is the full abstract presented at the American Physiology Summit 2023 meeting and is only available in HTML format. There are no additional versions or additional content available for this abstract. Physiology was not involved in the peer review process.

Rifaximin Treatment for Individual and Multiple Symptoms of Irritable Bowel Syndrome With Diarrhea: An Analysis Using New End Points

Rifaximin is indicated for the treatment of irritable bowel syndrome with diarrhea (IBS-D) in adults. The current aim was to evaluate rifaximin efficacy on individual and composite IBS-D symptoms using definitions not previously examined. Phase III post hoc analyses of two randomized, double-blind, placebo-controlled trials and the open-label phase of a randomized, double-blind, placebo-controlled trial were conducted. Adults with IBS-D received a 2-week course of rifaximin 550 mg TID. Individual and composite responses for abdominal pain (mean weekly improvements from baseline of ≥30%, ≥40%, or ≥50%), bloating (mean weekly improvements from baseline of ≥1 or ≥2 points; or ≥30%, ≥40%, or ≥50%), stool consistency (mean weekly average stool consistency score <3 or <4), and urgency (improvement from baseline of ≥30% or ≥40% in percentage of days with urgency) for ≥2 of the first 4 weeks after treatment, and weekly for 12 weeks, were assessed. Overall, 1258 patients from the double-blind trials (rifaximin [n = 624]; placebo [n = 634]) and 2438 from an open-label trial were analyzed. The percentage of bloating or urgency responders was significantly greater with double-blind rifaximin versus placebo (P ≤ 0.03). A significantly greater percentage of the double-blind group were composite abdominal pain and bloating responders versus placebo for all thresholds analyzed (P < 0.05). A significantly greater percentage of the double-blind group were tri-symptom composite end point responders (abdominal pain, bloating, and fecal urgency) versus placebo (P = 0.001). A significantly greater percentage of patients achieved response (≥30% composite tri-symptom threshold) with double-blind rifaximin versus placebo as early as 1 week posttreatment, with significance maintained through ≥5 weeks after treatment. Open-label results were consistent with those of the double-blind study. Rifaximin significantly improved multiple, concurrent IBS-D symptoms, using clinically relevant definitions of treatment response. Using a novel tri-symptom composite end point (ie, abdominal pain, bloating, fecal urgency), adults with IBS-D treated with a 2-week course of rifaximin were significantly more likely to be composite end point responders than those receiving placebo (≥30% or ≥40% threshold) for the three symptoms. Thus, rifaximin not only met current standard thresholds used for adjudication of responders in clinical trials but also achieved higher thresholds for many of these symptoms, suggesting potential for even more robust clinical improvements. gov identifiers: NCT00731679, NCT00724126, and NCT01543178.

S544 Rifaximin Improves Both Fecal Urgency and Stool Consistency in Adults With Irritable Bowel Syndrome With Diarrhea (IBS-D): A Composite Endpoint Analysis of Two Randomized, Phase 3 Trials

Introduction: For patients with IBS-D, in addition to loose stool consistency, fecal urgency is a common, bothersome symptom. The aim was to evaluate rifaximin for simultaneously improving symptoms of fecal urgency in addition to loose/watery stool consistency as a unique composite bowel symptom endpoint. Methods: A post hoc analysis was conducted with data from 2 identically designed, phase 3, randomized, double-blind trials. Adults with IBS-D, with screening daily mean stool consistency score of ≥3.5 (range, 1 “very hard”; 5 “watery”), took rifaximin 550 mg TID or placebo for 2 weeks, followed by a 4-week treatment-free phase to assess response. Fecal urgency was based on patient response to the daily question, “Have you felt or experienced a sense of urgency today?” Composite bowel symptom responders were defined as patients who simultaneously achieved a ≥30% decrease from baseline in the percentage of days with fecal urgency and had a mean weekly stool consistency score of < 4 for ≥2 of the first 4 post-treatment weeks. Data were analyzed using last observation carried forward; P values were calculated using the Cochran-Mantel-Haenszel method, adjusting for analysis center. Results: A total of 1258 adults (rifaximin [n=624], placebo [n=634]) were included (mean ± SD age, 45.9 ± 14.5 years; 72.3% female). Similar values at baseline were observed for rifaximin and placebo groups for the percentage of days with fecal urgency (82%), mean daily stool consistency score (3.9), and mean ± SD number of daily bowel movements (3.0 ± 1.5). A significantly greater percentage of patients treated with rifaximin were bowel symptom composite responders vs placebo for ≥2 of the first 4 weeks post-treatment (47.9% vs 39.3%, respectively; P=0.002). A higher percentage of responders with rifaximin was observed vs placebo when analyzed by week (Figure). A significantly higher percentage of patients who were bowel symptom composite responders during ≥2 of the first 4 weeks post-treatment maintained response during ≥3 of the additional 6 weeks of treatment-free follow up (Week 12) in rifaximin vs placebo groups (44.7% vs 36.1%; P=0.002). For the individual components of response, a significantly greater percentage of patients in rifaximin group were fecal urgency responders vs placebo (52.9% vs 43.1%; P< 0.001) or stool consistency responders (82.7% vs 77.8%; P=0.03). Conclusion: A 2-week course of rifaximin significantly and simultaneously improved fecal urgency and stool consistency vs placebo in adults with IBS-D.Figure 1.: Percentage of patients with ≥30% decrease from baseline in percentage of days with fecal urgency and mean weekly stool consistency score of < 4, by week *P< 0.05 vs placebo.

Double-blinded randomised placebo controlled trial of enterosgel (polymethylsiloxane polyhydrate) for the treatment of IBS with diarrhoea (IBS-D)

ObjectiveIrritable bowel syndrome with diarrhoea (IBS-D) is a common and challenging condition that significantly reduces quality of life. Enterosgel (polymethylsiloxane polyhydrate) is an intestinal adsorbent which sequesters harmful molecules and...

Comparison of the Effects of Abdominal Massage and Oral Administration of Sweet Almond Oil on Constipation and Quality of Life among Elderly Individuals: A Single-Blind Clinical Trial.

Background Constipation is a common digestive disorder in the elderly population, which has a considerable impact on various aspects of their lives. Traditional and complementary medicines are two common treatments for constipation. This study was aimed at comparing the effects of abdominal massage and oral administration of sweet almond oil on constipation and quality of life among elderly people. Methods In this single-blind study, 90 eligible elderly people were randomly selected according to ROME IV diagnostic criteria from October 2020 to May 2021 and were divided into three groups using block randomization (n = 30). In the oral consumption group, 126 ml sweet almond oil was administered during seven sessions held over two weeks (18 ml every other day). The abdominal massage group was provided with abdominal massage with the same amount of sweet almond oil during seven sessions in two weeks. Finally, the third group (i.e., the control group) received no interventions. Constipation was measured using the Constipation Assessment Scale (CAS) and the Bristol Stool Form Scale (BSFS) at baseline and on the 15th day of the intervention. Patient Assessment of Constipation-Quality of Life (PAC-QOL) was also applied before and after the intervention (day 15). The data were entered in to the SPSS 22 software and were analyzed using chi-square t-test, paired t-test, independent t-test, and ANOVA. p ≤ 0.05 was considered statistically significant. Results The results revealed a significant decrease in the CAS score in the oral consumption group (i.e., oral administration of sweet almond oil; from 7.81 ± 2.62 to 1.15 ± 1.08, p < 0.0003) compared to the abdominal massage group (i.e., abdominal massage; from 8 ± 2.57 to 2.26 ± 1.81, p < 0.0002) and the control group (from 7.73 ± 2.53 to 6 ± 2.74, p < 0.0002). Additionally, the stool consistency score in BSFS was significantly higher in the oral consumption group in comparison to the two other groups (p < 0.0003) before and after the intervention. Furthermore, the quality of life score decreased more significantly in the oral consumption group (from 75.04 ± 7.66 to 28.15 ± 3.30, p < 0.0003) than in the abdominal massage group (from 81.15 ± 5.15 to 43.26 ± 4.13, p < 0.0001) and the control group (from 79.62 ± 4.76 to 62.31 ± 6.40, p < 0.0008). Conclusion Since the oral administration of sweet almond oil and abdominal massage was highly influential in the participants' constipation scores and quality of life, these cost-effective methods with low complication rates are recommended to be used alongside other treatments in managing constipation among older adults.

Exocrine Pancreatic Insufficiency is Undiagnosed in Some Patients with Diarrhea-Predominant Irritable Bowel Syndrome Using the Rome IV Criteria.

Irritable bowel syndrome (IBS) is one of the most frequent disorders in clinical practice, with a mean 7.6-10.8% worldwide prevalence. A study showed that 6.1% of patients with diarrhea-predominant IBS (IBS-D) had severe exocrine pancreatic insufficiency (EPI). We aimed to identify the prevalence of EPI based on fecal elastase stool testing (Fel-1) in IBS-D and the clinical characteristics that may predict the diagnosis of EPI. Patients aged > 18years presenting to tertiary hospital outpatient clinics with IBS-D completed validated questionnaires and gave a stool sample where Fel-1 concentration was measured. Patients with Fel-1 < 100µg/g represented EPI and > 100 to < 200µg/g underwent testing for pancreatic pathology with laboratory and endoscopic ultrasound (EUS) evaluation. One hundred forty patients (mean age 60years, females 75.7%) were studied. EPI was found in 5% (95% CI 2.2-10.4), and pancreatic steatosis was the main EUS finding (71%). Dyspepsia was an independent factor associated with EPI (OR 34.7; 95% CI 4.95-366.37, p = 0.0007). After pancreatic enzyme replacement therapy (PERT), patients showed a significant improvement in the Bristol stool scale (p < 0.0001), bowel movements per day (p < 0.005), distension score (0.0009), pain score (0.0277) and IBS severity (0.0034). EPI is present in 5% of patients who fulfill Rome IV criteria for D-IBS, and dyspepsia was an independent symptom strongly associated with EPI. Pancreatic steatosis was the main endoscopic ultrasound finding. After PERT therapy, patients had significantly improved stool frequency, stool consistency, abdominal pain, distension and IBS severity score.

Effects of Milk Polar Lipids on Colitis Are Dependent on Dietary Fat Content

ObjectivesIn North America, over 1.5 million people suffer from inflammatory bowel disease (IBD), which includes ulcerative colitis and Crohn’s disease. Changes in environmental and lifestyle factors coinciding with westernization has driven a rapid acceleration in IBD prevalence worldwide. The objectives of this study were to identify how different milk lipids affect colitis disease activity, the colonic transcriptome, and the microbiome in a mouse model of chemical-induced colitis. MethodsMale and female C57BL6/J mice (n = 120) were randomized into either a low (5% w/w) milk fat (LFD) or high (21% w/w) milk fat diet (HFD) supplemented with either 0%, 1%, or 2% w/w of milk polar lipids (MPLs) for 3 weeks (n = 10/group/sex). Afterwards, colitis was induced using 1% dextran sodium sulfate (DSS) in drinking water for 5 days and regular drinking water was given for the final 5 days. Colons were used for histology, transcriptomics by RNA-sequencing, and real-time qRT-PCR, and cecal feces were collected for 16S rRNA sequencing for microbiome analysis. Disease Activity Index (DAI) was recorded daily consisting of a weight loss, bleeding, and stool consistency score. ResultsMPLs attenuated DAI score in HFD compared to control during the colitis induction and recovery phase, while MPLs in LFD exacerbated DAI during the recovery period. Colon transcriptomics showed that males fed HFD with MPLs had lower expression of genes associated with inflammatory signaling compared to the HFD without MPLs. Colons of the males fed LFD with MPLs had upregulated pathways involved in inflammatory cytokines and antimicrobial activity and downregulated pathways involved in cAMP signaling and extracellular matrix constituents. Fecal Verrucomicrobia was the most abundant bacterial phyla, while MPLs increased Proteobacteria and Bacteroidetes in LFD compared to HFD in males. Male mice had higher microbial diversity and MPLs increased alpha diversity measures. ConclusionsMPLs protected against colitis in mice fed HFD but promoted the disease under LFD conditions. These results suggest the influence of MPLs on colitis is dependent on dietary fat content. Funding SourcesThis research was supported by a USDA NIFA AFRI grant to C. Blesso.

Administration of an Anal Bulking Agent With Polyacrylate-Polyalcohol Copolymer Particles Versus Endoanal Electrical Stimulation With Biofeedback for the Management of Mild and Moderate Anal Incontinence: A Randomized Prospective Study

There are few treatment options for mild-to-moderate anal incontinence with isolated internal anal sphincter defects or anal incontinence without muscle damage. Less-invasive techniques are generally favored. To compare the results between the use of an anal bulking agent with polyacrylate-polyalcohol copolymer particles and endoanal electrical stimulation with biofeedback in patients with mild or moderate anal incontinence. This was a prospective parallel-group, single-institution, randomized clinical trial. This study was conducted in an ambulatory setting at the Colorectal Physiology Service of the Hospital das Clinicas, Medical School, University of Sao Paulo. This study included patients who had anal incontinence for >6 months with isolated internal anal sphincter muscle damage or absence of anatomical defects in the anorectal sphincter complex. Anal bulking agent and endoanal electrical stimulation with biofeedback. The primary outcome measure was the Cleveland Clinic Florida Fecal Incontinence Score, and the secondary outcome measures included quality of life, recommended procedures, and anorectal manometry. There were no significant between-group differences in mean age, sex, BMI, stool consistency, and Cleveland Clinic Florida Fecal Incontinence Score (p = 0.20) at baseline. After 12 months, the Cleveland Clinic Florida Fecal Incontinence Score was found to be significantly improved in patients treated with the bulking agent compared to those treated with electrical stimulation (mean, 6.2 vs 9.2; p = 0.002), though the anorectal manometry parameters did not change significantly. The mean anal Cleveland Clinic Florida Fecal Incontinence Score declined by 4.2 points in the bulking agent group compared to a decline of 0.8 in the electrical stimulation group (mean difference in decline: 3.4 points; 95% CI, 1.2-5.5). Quality-of life evaluation showed similar results between groups comparing baseline parameters with 12-month follow-up. The short follow-up period of 1 year, atypical method of biofeedback, and unmatched baseline in some of the quality-of-life scales between the 2 groups limited this study. In patients with mild or moderate anal incontinence, the Cleveland Clinic Florida Fecal Incontinence Score significantly improved in the bulking agent with polyacrylate-polyalcohol copolymer group compared with the endoanal electrical stimulation with biofeedback group. See Video Abstract at http://links.lww.com/DCR/B938. ANTECEDENTES:Hasta la fecha, existen pocas opciones de tratamiento para la incontinencia anal de leve a moderada con defectos aislados del esfínter anal interno o la incontinencia anal sin daño muscular. Por lo general, se prefieren técnicas menos invasivas.OBJETIVO:El objetivo fue comparar los resultados entre el uso de un gel intra-anal con partículas de copolímero de poliacrilato-polialcohol y la estimulación eléctrica endoanal con ejercicios anales en pacientes con incontinencia anal leve o moderada.DISEÑO:Este fue un ensayo clínico aleatorio prospectivo de grupos paralelos, de una institución, realizado en cuatro etapas: base, procedimientos, postratamiento temprano y tardío.AJUSTE:Este estudio se realizó en el ambulatorio de Fisiología Colorrectal del Servicio de Coloproctología del Hospital das Clínicas, Facultad de Medicina, Universidad de São Paulo.PACIENTES:Paciente con incontinencia anal con más de 6 meses, con daño muscular aislado del esfínter anal interno o ausencia de defectos anatómicos en el esfínter anorrectal.INTERVENCIONES:Las intervenciones incluyeron la inyección del gel intra-anal y estimulación eléctrica endoanal con ejercicios anales.PRINCIPALES MEDIDAS DE RESULTADO:Indice de incontinencia fecal (Cleveland Clinic Florida), Indice de calidad de vida, los procedimientos recomendados y la manometría anorrectal.RESULTADOS:No hubo diferencias significativas entre los grupos en cuanto a la edad media, el sexo, el índice de masa corporal, la consistencia de las heces y la puntuación de incontinencia fecal (p = 0,20) al inicio del estudio. Después de 12 meses, la puntuación de incontinencia fecal mejoró significativamente en los pacientes tratados con el el gel intra-anal (media = 6,2) en comparación con los tratados con estimulación eléctrica (media = 9,2; p = 0,002), aunque los parámetros de manometría anorrectal no mejoraron significativamente. La puntuación anal media de incontinencia fecal disminuyó 4,2 puntos en el grupo del Gel intra-anal en comparación con 0,8 en el grupo de estimulación eléctrica (diferencia media en la disminución: 3,4 puntos; IC del 95%: 1,2 a 5,5). La evaluación de la calidad de vida mostró resultados similares entre los grupos que compararon los parámetros iniciales con un seguimiento de 12 meses.LIMITACIONES:Breve período de seguimiento de un año, métodos diferentes de ejercicios anales y línea de base sin igual en algunas de las escalas de calidad de vida entre los dos grupos.CONCLUSIONES:En pacientes con incontinencia anal leve y moderada, la puntuación de incontinencia fecal mejoró significativamente en el grupo de gel intra-anal con copolímero de poliacrilato-polialcohol en comparación con la estimulación eléctrica endoanal. Consulte Video Resumen en http://links.lww.com/DCR/B938. (Traducción- Dr Leonardo Alfonso Bustamante-Lopez).

Effect of a Probiotic Mixture in Captive Cheetahs (Acinonyx Jubatus) with Gastrointestinal Symptoms-A Pilot Study.

Simple SummaryIn recent years, many studies have demonstrated the effectiveness of probiotics in acute and chronic gastrointestinal disorders in both humans and animals. The objective of this study is to evaluate the effect of a specific probiotic mixture in cheetahs. In the wild, cheetah populations have drastically reduced due to habitat destruction, human–wildlife conflict and illegal wildlife trade. In captivity, chronic gastrointestinal diseases have a high prevalence. Based on our results, it can be concluded that probiotics may be helpful as a dietary supplement in cheetahs suffering from gastrointestinal disease.Cheetahs (Acinonyx jubatus) are classified as “vulnerable” species due to the low numbers persisting in the wild. Gastrointestinal diseases are very common in this species when they are kept in captivity, in particular gastritis. Clinical signs are predominantly characterized by vomiting, diarrhea, weight loss and anorexia. In this study, we evaluated the efficacy of a multi-strain probiotic in two groups of cheetahs: Group A (n = 4)—rescued cheetahs housed at the Cheetah Conservation Fund (Otjiwarongo, Namibia); Group B (n = 9)—captive cheetahs housed in Italian zoos. Animals showed gastrointestinal signs of different severity, and were positive for Helicobacter spp., detected by PCR in stool samples. Two sachets of probiotic formulation were administered to all cheetahs once a day for 21 consecutive days. Clinical conditions (appetite loss, vomiting, stool consistency and Body Condition Score) before (T0) and after 21 days of probiotic administration (T1) were then compared using a simplified Feline Chronic Enteropathy Activity Index (FCEAI) score. A slight but not significant improvement in the scores was observed in Group A, which had mild intestinal symptoms, while a significant decrease in vomiting and stool consistency (**p < 0.01) scores was observed in Group B, which had more pronounced symptoms. Results suggest that high concentrations of live probiotics can be of help in managing gastrointestinal signs in cheetahs.

CELLULAR AND MOLECULAR IMPACT OF THE MELANOCORTIN RECEPTOR AGONIST PL8177 IN DEXTRAN SODIUM SULFATE (DSS)-INDUCED COLITIS IN RATS

Abstract INTRODUCTION The melanocortin 1 receptor (MC1r)–specific agonist PL8177 and its main metabolite PL8435 have demonstrated MC1r binding affinity and functional activity that mirrors that of α-melanocyte stimulating hormone (a-MSH). a-MSH has been demonstrated to be effective in reducing inflammation in numerous experimental models. This study investigates the effects of PL8177 on inflammation, cell population composition, and gene and protein expression in colons from a DSS–induced rat model of colitis. The objective is to determine the effectiveness of PL8177 in this model and to characterize its underlying mechanism of action. METHODS Male Wistar rats received 5% DSS in drinking water for 3 days to induce colitis. Rats in the sham group received drinking water only (each group n=6). The other groups received vehicle control (placebo)–filled capsules; PL8177-filled capsules at 20, 50, and 100 μg/animal (by oral gavage); or oral mesalazine (positive control). At termination on day 8, 24 hours after the last dosing, colon tissues were harvested, dissected and snap frozen with liquid nitrogen. Colon samples were analyzed for cytokine levels, single nuclei RNA-seq, and data-independent acquisition tandem mass spectrometry (LC/MS DIA). Colitis was assessed by a disease activity index (diarrhea and rectal bleeding), colon length shortening, colon weight gain, and histopathological assessment. The total colitis index, was used to assess inflammatory damage. RESULTS Colitis was induced in rats treated with DSS. Oral PL8177 50 μg/animal treatment showed a significant improvement in colon weight (53% reduction), stool consistency, and fecal occult blood score compared to vehicle. There was a significant (P&amp;lt;0.05) improvement in the total colitis index for the PL8177 100-μg group vs vehicle control group. All PL8177-cohorts showed greater improvement in the total colitis index compared to the mesalazine-treated cohort. PL8177 50 μg/animal showed a significant improvement in colon weight (53% reduction), while mesalazine treatment was associated with significant reduction in colon length, but only moderate improvement (35%) in colon weight. Changes in the cellular population compositions, gene expression changes and protein level data will be presented and discussed at the conference. CONCLUSION Oral PL8177 treatment of inflamed colon showed significant improvement in markers of colitis in the rat model compared to the placebo and mesalazine control groups supporting the aim of treating inflammatory bowel disease in humans. Genomic and proteomic data will be interpreted in the context of disease change to identify alterations in immune and cellular states of the experimental colons.

김치에서 분리된 Latilactobacillus curvatus 장염증 완화 작용

We focused on the anti-inflammatory properties of <italic>Latilactobacillus curvatus</italic>, formerly called <italic>Lactobacillus curvatus</italic>, isolated from kimchi. In a mouse model of dextran sulfate sodium (DSS)-induced colitis, treatment with <italic>L. curvatus</italic> significantly decreased the colitis by inhibiting the expression of a proinflammatory cytokine and receptor that disrupt intestinal epithelial structural integrity. The disease activity index combined scores for weight loss, stool consistency, and bleeding showed that disease activity was markedly lower in the DSS+ probiotics group. Histological analyses showed that treatment with <italic>L. curvatus</italic> strains protected the structural integrity of the intestinal epithelial layer and mucin-secreting goblet cells from DSS-induced damage, with only slight infiltration of immune cells. In serum and DSS-treated colon tissues, mRNA expression levels of IL-6, TNF R1, iNOS, and COX2 of <italic>L. curvatus</italic>-treated group were significantly suppressed. These results indicated that <italic>L. curvatus</italic> ameliorates the colitis in intestine and reduces IBD pathogenesis of host.

Efficacy and safety of lubiprostone for the treatment of functional constipation in Chinese adult patients: A multicenter, randomized, double-blind, placebo-controlled trial.

Functional constipation is a gastrointestinal disorder prevalent around the world. Lubiprostone is the first locally acting type-2 chloride channel activator to be used for treating constipation. This study aimed to evaluate the efficacy and safety of lubiprostone in Chinese adults with functional constipation. This was a multicenter, randomized, double-blind, placebo-controlled study. Patients with functional constipation were randomized to receive either lubiprostone (24 mcg twice daily) or placebo for 4 weeks. The primary end-point was the frequency of spontaneous bowel movements (SBMs) during the first week of treatment. The secondary end-points included the median time of the first SBM, SBM frequency at weeks 2, 3 and 4, weekly response rate of SBMs, the stool consistency score and average number of complete spontaneous bowel movements (CSBMs) per week. In total, 259 patients were randomized, with 130 in the lubiprostone group and 129 in the placebo group. SBM frequency was higher in the lubiprostone group (4.88 ± 4.09/wk) than that in the placebo group (3.22 ± 2.01/wk) at week 1 (P < 0.0001). SBM frequency was also higher in the lubiprostone group at weeks 2, 3 and 4. The average number of CSBMs and the stool consistency score in the lubiprostone group were significantly higher than that in the placebo group at each week. No drug-related serious adverse events (AEs) occurred. The most commonly reported AE was nausea. Lubiprostone was superior to placebo in treating Chinese patients with functional constipation, together with good safety profile.