Marker Of Intestinal Inflammation Research Articles

Calprotectin, Biomarker of Depression in Patients with Inflammatory Bowel Disease?

Background and Objectives: Calprotectin is a marker for intestinal inflammation. Recent research suggests a link between inflammation and depression. This study assessed the association between the levels of calprotectin in patients from South-Eastern Europe and the severity of depression, anxiety, and quality of life. Materials and Methods: This cross-sectional study included 30 confirmed patients with Crohn's disease (CD) and ulcerative colitis (UC) who were assessed using clinical interviews for determining the severities of mental disorders (i.e., depression severity-PHQ-9, anxiety-GAD-7) and the quality of life (EQ-5D). Stool samples were collected from all participants for measuring their levels of calprotectin. Results: The level of calprotectin is correlated with PHQ-9 (ρ = 0.416, p = 0.022) and EQ-5D (ρ = -0.304, p = 0.033) but not with GAD 7 (ρ = 0.059, p = 0.379). Calprotectin levels in patients with mild, moderate, and moderately severe depression were significantly higher than in patients with minimal depression (198 µg/g vs. 66,9 µg/g, p = 0.04). Calprotectin level was corelated with the following depressive symptoms: autolytic ideation (ρ = 0.557, p = 0.001), fatigue (ρ = 0.514, p = 0.002), slow movement (ρ = 0.490, p = 0.003), and sleep disorders (ρ = 0.403, p = 0.014). Calprotectin was an independent predictor of depression with an odds ratio of 1.01 (95%: 1.002-1.03, p < 0.01). An ROC analysis showed that a level of calprotectin of 131 µg/g or higher has a sensitivity of 82%, a specificity of 61%, and an accuracy of 70% for predicting depression. In this study, no significant correlations were found between calprotectin level and anxiety. Conclusions: Calprotectin levels are associated with the severity of depression, and checking for a calprotectin level of 131 µg/g or higher may be a potential accessible screening test for depression in patients with inflammatory bowel disease.

Assessment of Intestinal Permeability and Inflammation Bio-Markers in Patients with Rheumatoid Arthritis.

Increased intestinal permeability and inflammation, both fueled by dysbiosis, appear to contribute to rheumatoid arthritis (RA) pathogenesis. This single-center pilot study aimed to investigate zonulin, a marker of intestinal permeability, and calprotectin, a marker of intestinal inflammation, measured in serum and fecal samples of RA patients using commercially available kits. We also analyzed plasma lipopolysaccharide (LPS) levels, a marker of intestinal permeability and inflammation. Furthermore, univariate, and multivariate regression analyses were carried out to determine whether or not there were associations of zonulin and calprotectin with LPS, BMI, gender, age, RA-specific parameters, fiber intake, and short-chain fatty acids in the gut. Serum zonulin levels were more likely to be abnormal with a longer disease duration and fecal zonulin levels were inversely associated with age. A strong association between fecal and serum calprotectin and between fecal calprotectin and LPS were found in males, but not in females, independent of other biomarkers, suggesting that fecal calprotectin may be a more specific biomarker than serum calprotectin is of intestinal inflammation in RA. Since this was a proof-of-principle study without a healthy control group, further research is needed to validate fecal and serum zonulin as valid biomarkers of RA in comparison with other promising biomarkers.

Faecal calprotectin: Marker of intestinal inflammatory process in anorexia nervosa? A preliminary study.

Anorexia Nervosa (AN) is a serious and potentially lethal mental disorder characterised by a deliberate quest to reduce one's weight. It can have multiple physical and psychological consequences. The clinical presentation of AN can include gastrointestinal symptoms, however, the pathophysiology of these symptoms in the context of AN remains uncertain. It is hypothesised that patients with AN may have an increase in intestinal permeability, which could lead to an increase in faecal calprotectin (fCP), a marker of intestinal inflammation. No relation between AN and elevation of fCP has been previously described in literature. Eight patients hospitalised for AN have a dosage of fCP. Calprotectine was found to be elevated in 50% of cases, with or without any underlying comorbid gastrointestinal disease. Only the duration of illness tended to be associated with the increase in fCP suggesting a greater alteration as a function related to the time of denutrition. Although these findings provide insights in the potential pathophysiology of gastrointestinal symptoms in AN, further studies that evaluate the factors associated with elevated fCP in patients with AN are needed.

Low-dose glyphosate exposure alters gut microbiota composition and modulates gut homeostasis

The widespread use of glyphosate, a broad-spectrum herbicide, has resulted in significant human exposure, and recent studies have challenged the notion that glyphosate is safe for humans. Although the link between disease states and glyphosate exposure is increasingly appreciated, the mechanistic links between glyphosate and its toxic effects on human health are poorly understood. Recent studies have suggested that glyphosate may cause toxicity through modulation of the gut microbiome, but evidence for glyphosate-induced gut dysbiosis and its effect on host physiology at doses approximating the U.S. Acceptable Daily Intake (ADI = 1.75 mg/kg body weight) is limited. Here, utilizing shotgun metagenomic sequencing of fecal samples from C57BL/6 J mice, we show that glyphosate exposure at doses approximating the U.S. ADI significantly impacts gut microbiota composition. These gut microbial alterations were associated with effects on gut homeostasis characterized by increased proinflammatory CD4+IL17A+ T cells and Lipocalin-2, a known marker of intestinal inflammation.

Characterization of Early and Late Damage in a Mouse Model of Pelvic Radiation Disease.

Pelvic radiation disease (PRD), a frequent side effect in patients with abdominal/pelvic cancers treated with radiotherapy, remains an unmet medical need. Currently available preclinical models have limited applications for the investigation of PRD pathogenesis and possible therapeutic strategies. In order to select the most effective irradiation protocol for PRD induction in mice, we evaluated the efficacy of three different locally and fractionated X-ray exposures. Using the selected protocol (10 Gy/day × 4 days), we assessed PRD through tissue (number and length of colon crypts) and molecular (expression of genes involved in oxidative stress, cell damage, inflammation, and stem cell markers) analyses at short (3 h or 3 days after X-ray) and long (38 days after X-rays) post-irradiation times. The results show that a primary damage response in term of apoptosis, inflammation, and surrogate markers of oxidative stress was found, thus determining a consequent impairment of cell crypts differentiation and proliferation as well as a local inflammation and a bacterial translocation to mesenteric lymph nodes after several weeks post-irradiation. Changes were also found in microbiota composition, particularly in the relative abundance of dominant phyla, related families, and in alpha diversity indices, as an indication of dysbiotic conditions induced by irradiation. Fecal markers of intestinal inflammation, measured during the experimental timeline, identified lactoferrin, along with elastase, as useful non-invasive tools to monitor disease progression. Thus, our preclinical model may be useful to develop new therapeutic strategies for PRD treatment.

Routine antibiotics for infants less than 6 months of age with growth failure/faltering: a systematic review

ObjectiveThis systematic review commissioned by WHO aimed to synthesise evidence from current literature on the effects of systematically given, routine use of antibiotics for infants under 6 months of age...

Fecal Microbiota Restoration Modulates the Microbiome in Inflammation-Driven Colorectal Cancer.

Chronic inflammation of the colon (colitis) is a known risk factor for inflammatory-driven colorectal cancers (id-CRCs), and intestinal microbiota has been implicated in the etiology of id-CRCs. Manipulation of the microbiome is a clinically viable therapeutic approach to limiting id-CRCs. To understand the microbiome changes that occur over time in id-CRCs, we used a mouse model of id-CRCs with the treatment of azoxymethane (AOM) and dextran sodium sulfate (DSS) and measured the microbiome over time. We included cohorts where the microbiome was restored using cage bedding swapping and where the microbiome was depleted using antibiotics to compare to untreated animals. We identified consistent increases in Akkermansia in mice receiving horizontal microbiome transfer (HMT) via cage bedding swapping, while the control cohort had consistent longitudinal increases in Anaeroplasma and Alistipes. Additionally, fecal lipocalin-2 (Lcn-2), a marker of intestinal inflammation, was elevated in unrestored animals compared to restored and antibiotic-treated counterparts following HMT. These observations suggest a potential role for Akkermansia, Anaeroplasma, and Alistipes in regulating colonic inflammation in id-CRCs.

Faecal markers of intestinal inflammation in slum infants following yogurt intervention: A pilot randomized controlled trial in Bangladesh

IntroductionWe evaluated the effects of yogurt supplementation and nutrition education to low educated mothers on infant-gut health at an early age.MethodsWe designed a three-arm pilot randomized controlled trial with 162 infants aged 5-6 months and at risk of stunting (LAZ ≤-1 SD and &amp;gt;-2 SD at enrollment) living in slum areas in Dhaka, Bangladesh. Eligible children were randomized to receive, 1) nutrition education, 2) yogurt supplementation plus nutrition education or 3) usual care. Three faecal inflammatory biomarkers alpha-1 antitrypsin (AAT), myeloperoxidase (MPO), and neopterin (NEO) were measured before and after three months of yogurt feeding. ResultsAt the end of three months, there were no significant differences in the biomarker concentrations between the yogurt plus group and control. Compared to control, the adjusted mean faecal NEO concentration decreased by 21% (NEO: RR 0.79, 95% CI: 0.60, 1.04) and the adjusted mean faecal AAT concentration decreased by 8% (AAT: RR 0.92, 95% CI: 0.69, 1.22); whereas, the adjusted mean faecal MPO concentration increased by 14% (MPO: RR 1.14, 95% CI: 0.62, 2.09). Such changes were not apparent in the education only group. DiscussionAfter a three-month trial of daily yogurt feeding to children at risk of stunting and infant feeding education to their mothers, reduction in one inflammatory biomarker reached close to statistical significance, but not all of the measured biomarkers. The study did not finish its endline measurements at 6-month as designed due to COVID 19 pandemic. This has greatly impacted the interpretation of the results as we could not establish a decreasing trend in biomarker concentration with continued yogurt feeding.

STANDARDIZATION ISSUES FOR FECAL CALPROTECTIN MEASUREMENT IN INFLAMMATORY BOWEL DISEASE

Fecal calprotectin (FC) is a non-invasive marker of intestinal inflammation that is often used to guide therapeutic decisions in patients with inflammatory bowel disease (IBD). Each step in FC measurement can influence the results, leading to misinterpretation and potentially affecting the management of patients with IBD. To date, FC measurements are highly heterogeneous, and none of the existing methods is generally accepted as a standard. &lt;b&gt;Aim:&lt;/b&gt; to provide a clear position on the preanalytical and analytical steps of FC measurement and to minimize the risk of misinterpretation. &lt;b&gt;Materials and methods.&lt;/b&gt; A systematic search of the scientific literature was carried out in the PubMed/MEDLINE, EMBASE and Cochrane databases until June 2021 to identify all studies reporting data on FC measurement (for the key phrases "fecal markers of inflammation", "calprotectin", "inflammatory bowel diseases"). &lt;b&gt;Results.&lt;/b&gt; Based on available data, quantitative tests should be preferred to measure FC; FC measurements should always be performed using the same method, and factors affecting his levels should be taken into account when interpreting results. &lt;b&gt;Conclusion.&lt;/b&gt; FC concentrations determine treatment decisions by physicians. Although FC is playing an increasingly important role in the management of IBD patients, large multicenter studies should be conducted to determine the reproducibility and to confirm the diagnostic accuracy of the available FC tests.

A37 FECAL CALPROTECTIN IN A PEDIATRIC, POPULATION-BASED STUDY: UTILITY IN DIAGNOSIS AND INFLAMMATORY BOWEL DISEASE MONITORING

Abstract Background Fecal calprotectin (FC) is a sensitive marker of intestinal inflammation, and is used to both discriminate inflammatory bowel disease (IBD) from non-IBD patients and to monitor patients with IBD. It is unclear whether normal values established in adult patients are applicable in pediatrics. Purpose To evaluate FC’s ability to differentiate IBD from non-IBD pediatric patients, and to understand factors influencing FC in pediatric IBD(pIBD). Method Stool FC samples collected on all patients&amp;lt;19 years of age in British Columbia(BC) from May 2020 to August 2022 were run using a Buhlmann ELISA at BC Children’s Hospital(BCCH). The BCCH GI database identified patients with IBD. FC’s ordered by adult IBD providers and patients awaiting endoscopy were excluded. The remaining samples were analysed as non-IBD. The sensitivity(Sn), negative predictive value(NPV) and false positive(FP) of FC were evaluated; comparisons were made using the Wilcoxon rank-sum test and chi-squared. Result(s) 3506 FC samples met inclusion criteria: 1853 IBD and 1653 non-IBD. 221 IBD samples were from prior to diagnosis, with median (IQR) FC 2615ug/g(1090-4183); median FC for non-IBD patients was 54ug/g(24-122). Using the Buhlmann "normal" cutoff of 80ug/g, the Sn was 0.991 (NPV 0.998) with a FP rate of 37%. Young patients were more likely to have FP's: &amp;lt;6yo's (n=305) had a FP rate of 42% vs 36% in those &amp;gt;6yo (n=1348)(p=0.035). With a FC cutoff of 160ug/g, Sn was 0.973 (NPV 0.996), with a FP rate of 20% (24% &amp;lt;6yo vs 19% &amp;gt;6yo, p=0.025). At a threshold of 250ug/g, Sn was 0.959 (NPV 0.994) with a FP rate of 13% (18% &amp;lt;6yo vs 12% &amp;gt;6yo, p=0.01). For patients &amp;lt;2yo, all 4 new IBD diagnosis had FC&amp;gt;1900ug/g. In the non-IBD population (n=69 samples &amp;lt;2yo), the FP rate was 52%, 30%, and 22% using a threshold of 80, 160, and 250ug/g, respectively. Evaluating FC as a disease-monitoring tool in IBD (667 patients, 1632 samples) found that at 6, 12, 18, and 24+ months post diagnosis, FC decreased from 750(159-1883), 505(110-1566), 351(87-1379), to 308ug/g(85-1129), respectively. Similarly, the proportion of FC’s &amp;lt;250ug/g increased from 4.1% at diagnosis to 30%, 39.7%, 41.5%, 47% during the follow up period. Patients with UC/IBD-U had higher FC’s, and were less likely to achieve FC&amp;lt;250ug/g. By 12 months post diagnosis, median FC of CD patients was 347ug/g(96-1150) and UC/IBD-U was 745ug/g(191-2017)(p=0.036), and at 18 months, CD 273ug/g(61-902) vs UC/IBD-U 932ug/g(144-2229)(p&amp;lt;0.001). At 2+yrs, median FC for CD patients was 259ug/g(76-1038) vs 387ug/g(108-1577) for UC/IC (p=0.017). Patients cared for by an IBD specialist had better FC outcomes vs those managed by non-IBD GIs: median FC at 12 months was 246ug/g(n=79) vs 677ug/g(n=153)(p=0.002), with 51% vs 34% achieving FC&amp;lt;250(p=0.014). Similarly, at 2+yrs post diagnosis, median FC was 243ug/g(n=437) vs 356ug/g(n=407)(p=0.02). Conclusion(s) Higher FC thresholds are likely required in younger populations compared to established adult cutoffs. In this pIBD cohort, &amp;lt;50% achieve FC levels &amp;lt;250ug/g. Please acknowledge all funding agencies by checking the applicable boxes below None Disclosure of Interest None Declared

Genes mcr improve the intestinal fitness of pathogenic E. coli and balance their lifestyle to commensalism

BackgroundThe plasmid-mediated resistance gene mcr-1 confers colistin resistance in Escherichia coli and paves the way for the evolution to pan-drug resistance. We investigated the impact of mcr-1 in gut colonization in the absence of antibiotics using isogenic E. coli strains transformed with a plasmid encoding or devoid of mcr-1.ResultsIn gnotobiotic and conventional mice, mcr-1 significantly enhanced intestinal anchoring of E. coli but impaired their lethal effect. This improvement of intestinal fitness was associated with a downregulation of intestinal inflammatory markers and the preservation of intestinal microbiota composition. The mcr-1 gene mediated a cross-resistance to antimicrobial peptides secreted by the microbiota and intestinal epithelial cells (IECs), enhanced E. coli adhesion to IECs, and decreased the proinflammatory activity of both E. coli and its lipopolysaccharides.ConclusionOverall, mcr-1 changed multiple facets of bacterial behaviour and appeared as a factor enhancing commensal lifestyle and persistence in the gut even in the absence of antibiotics.69sWK-11jgdNNSMi1guqFoVideo

497. Fecal cytokine profiling and markers of intestinal inflammation in Aotus nancymaae diarrhea model for enteropathogens

Abstract Background Naval Medical Research Unit 6 (NAMRU-6) established an animal model that closely resembles diarrheal diseases caused by Shigella, Campylobacter, and enterotoxigenic Escherichia coli (ETEC) in humans. These enteropathogens cause considerable mortality due to diarrhea in children and morbidity in travelers and military personnel deployed to regions of high prevalence. The successful oral challenge model developed in Aotus nancymaae, a New World monkey species, for Shigella, Campylobacter, and ETEC results in reproducible diarrhea attack rates of ≥70%. This model has been fundamental for the development and evaluation of new vaccine candidates. Many new approaches in vaccine development focus on stimulating antibodies against specific antigens expressed by these enteropathogens. Recent studies use the Aotus diarrhea model to evaluate new passive therapeutic and prophylactic treatments to prevent infection, inflammation, or diarrhea. However, the immune response and intestinal inflammation by the main enteropathogens are not clearly defined. Methods This study investigates how the cytokines and fecal markers of intestinal inflammation respond to gastroenteritis caused by Shigella, Campylobacter and ETEC in Aotus. Twenty-nine fecal cytokines (FC) were measured during diarrhea induced by Shigella flexneri (N = 8), Campylobacter jejuni (N=8), and ETEC (N = 8). Results Of note, both IL-1β and IL-15 were significantly increased at 24 hours after ETEC challenge. In contrast, when an infection with Shigella flexneri occurs, a significant increase in cytokines and chemokines such as MIF, MIP-1α and MIP-1β are observed 24 hours after challenge. While animals challenged with Campylobacter jejuni produce an increase in IL-1β 24 hours after challenge and an increase in cytokines MIF, MIP-1α and MIP-1β 4 days after challenge. Conclusion There is nonspecific upregulation of TH1/TH17 effector cytokines and those known to mediate intestinal barrier damage. The FC profiles have a different behavior between the three enteropathogens. This provides new insights into gut-specific immune alterations in the Aotus diarrhea model, which will help improve the design of new prophylactic and therapeutic treatments against diarrhea. Disclosures All Authors: No reported disclosures.

Fecal calprotectin in predicting small bowel capsule endoscopy findings in pediatric patients with known Crohn's disease.

Fecal calprotectin (FC) has been proposed as a noninvasive surrogate marker of intestinal inflammation in inflammatory bowel disease. This study aimed to assess the capability of FC in predicting small bowel capsule endoscopy (SBCE) findings in pediatric patients with known Crohn’s disease (CD). We retrieved data of consecutive patients aged 2 to 17 years old with established CD who underwent SBCE from Janurary 2017 to April 2020 and had endoscopic remission on ileocolonoscopy. Sixty-eight patients were included in the analysis. There were 13 patients with a weighted pediatric CD activity index ≥ 12.5, 47 patients with FC ≥ 200 µg/g, and 45 patients with significant small bowel (SB) inflammation [Lewis score (LS) ≥ 135]. The LS correlated weakly with FC (R = 0.30, P < .05). The area under the curve of FC as a surrogate diagnostic test for LS ≥ 135 was 0.691, and the optimal FC cutoff values were 242 µg/g with the corresponding sensitivity and specificity of 78% and 65%, respectively. The area under the curve of FC for moderate-to-severe inflammatory activity in the SB was 0.718. In patients with FC level ≥ 670 µg/g, LS ≥ 790 was found in 33% (9/27) of patients, with the sensitivity and specificity of 69% and 67%, respectively. FC may be used to predict SB mucosal inflammation in pediatric patients with confirmed CD having endoscopic remission on ileocolonoscopy.

Fecal Lcn-2 level is a sensitive biological indicator for gut dysbiosis and intestinal inflammation in multiple sclerosis.

Multiple Sclerosis (MS) has been reported to be associated with intestinal inflammation and gut dysbiosis. To elucidate the underlying biology of MS-linked gut inflammation, we investigated gut infiltration of immune cells during the development of spontaneous experimental autoimmune encephalomyelitis (EAE) in humanized transgenic (Tg) mice expressing HLA-DR2a and human T cell receptor (TCR) specific for myelin basic protein peptide (MBP87-99)/HLA-DR2a complexes. Strikingly, we noted the simultaneous development of EAE and colitis, suggesting a link between autoimmune diseases of the central nervous system (CNS) and intestinal inflammation. Examination of the colon in these mice revealed the infiltration of MBP-specific Th17 cells as well as recruitment of neutrophils. Furthermore, we observed that fecal Lipocalin-2 (Lcn-2), a biomarker of intestinal inflammation, was significantly elevated and predominantly produced by the gut-infiltrating neutrophils. We then extended our findings to MS patients and demonstrate that their fecal Lcn-2 levels are significantly elevated compared to healthy donors (HDs). The elevation of fecal Lcn-2 levels correlated with reduced bacterial diversity and increased levels of other intestinal inflammation markers including neutrophil elastase and calprotectin. Of interest, bacteria thought to be beneficial for inflammatory bowel disease (IBD) such as Anaerobutyricum, Blautia, and Roseburia, were reduced in fecal Lcn-2-high MS patients. We also observed a decreasing trend in serum acetate (a short-chain fatty acid) levels in MS Lcn-2-high patients compared to HDs. Furthermore, a decrease in the relative abundance of Blautia massiliensis was significantly associated with a reduction of acetate in the serum of MS patients. This study suggests that gut infiltration of Th17 cells and recruitment of neutrophils are associated with the development of gut dysbiosis and intestinal inflammation, and that fecal Lcn-2 level is a sensitive biological indicator for gut dysbiosis in multiple sclerosis.

A hydrogen-sulfide derivative of mesalamine reduces the severity of intestinal and lung injury in necrotizing enterocolitis through endothelial nitric oxide synthase.

Necrotizing enterocolitis (NEC) remains a devastating disease that affects preterm infants. Hydrogen sulfide (H2S) donors have been shown to reduce the severity of NEC, but the optimal compound has yet to be identified. We hypothesized that oral H2S-Mesalamine (ATB-429) would improve outcomes in experimental NEC, and its benefits would be dependent on endothelial nitric oxide synthase (eNOS) pathways. NEC was induced in 5-day-old wild-type (WT) and eNOS knockout (eNOSKO) pups by formula feeding and stress. Four groups were studied in both WT and eNOSKO mice: 1) breastfed controls, 2) NEC, 3) NEC + 50 mg/kg mesalamine, and 4) NEC + 130 mg/kg ATB-429. Mesalamine and ATB-429 doses were equimolar. Pups were monitored for sickness scores and perfusion to the gut was measured by Laser Doppler Imaging (LDI). After euthanasia of the pups, intestine and lung were hematoxylin and eosin-stained and scored for injury in a blind fashion. TLR4 expression was quantified by Western blot and IL-6 expression by ELISA. P < 0.05 was significant. Both WT and eNOSKO breastfed controls underwent normal development and demonstrated milder intestinal and pulmonary injury compared with NEC groups. For the WT groups, ATB-429 significantly improved weight gain, reduced clinical sickness score, and improved perfusion compared with the NEC group. In addition, WT ATB-429 pups had a significantly milder intestinal and pulmonary histologic injury when compared with NEC. ATB-429 attenuated the increase in TLR4 and IL-6 expression in the intestine. When the experiment was repeated in eNOSKO pups, ATB-429 offered no benefit in weight gain, sickness scores, perfusion, intestinal injury, pulmonary injury, or decreasing intestinal inflammatory markers. An H2S derivative of mesalamine improves outcomes in experimental NEC. Protective effects appear to be mediated through eNOS. Further research is warranted to explore whether ATB-429 may be an effective oral therapy to combat NEC.

Targeting the Gut Microbiota and Host Immunity with a Bacilli-Species Probiotic during Antibiotic Exposure in Mice

Antibiotic therapy is necessary for the treatment of bacterial infections; however, it can also disrupt the balance and function of commensal gut microbes and negatively affect the host. Probiotics have been tested as a means to counteract the negative effects of antibiotic therapy, but many probiotics are also likely destroyed by antibiotics when taken together. Here we aimed to test the efficacy of a non-pathogenic spore-forming Bacillus-species containing a probiotic blend provided during antibiotic therapy on host immune defenses in mice. Mice were exposed to antibiotics and supplemented with or without the probiotic blend and compared to control mice. Fecal and cecal contents were analyzed for gut microbes, and intestinal tissue was tested for the expression of key enzymes involved in vitamin A metabolism, serum amyloid A, and inflammatory markers in the intestine. The probiotic blend protected against antibiotic-induced overgrowth of gram-negative bacteria and gammaproteobacteria in the cecum which correlated with host immune responses. Regional responses in mRNA expression of enzymes involved with vitamin A metabolism occurred between antibiotic groups, and intestinal inflammatory markers were mitigated with the probiotic blend. These data suggest prophylactic supplementation with a spore-forming Bacillus-containing probiotic may protect against antibiotic-induced dysregulation of host immune responses.

Bowel wall MRI T1 relaxation estimates for assessment of intestinal inflammation in pediatric Crohn's disease.

To compare bowel wall T1 relaxation estimates in young patients with newly diagnosed ileal CD to healthy control participants, characterize their change over time in response to biologic medical therapy, and evaluate their associations with clinical markers of intestinal inflammation. Patients with newly diagnosed ileal CD and healthy control participants were prospectively recruited between December 2018 and October 2021. Patients underwent research MRI examinations of the bowel at baseline and at 6-weeks and 6-months into biologic medical treatment; control participants underwent single MRI examinations. MRI examinations included native T1 relaxometry of the terminal ileum using a modified Look-Locker inversion recovery (MOLLI) sequence. T1 estimates were measured on scanner-generated parametric maps. Clinical markers of intestinal inflammation were recorded at each visit. Group differences were assessed using the Mann-Whitney U test; the Friedman test was used to assess longitudinal changes in T1 estimates. Spearman correlation was used to evaluate associations between T1 estimates and inflammatory markers. Nineteen participants with CD (12 males; median age 14years) and 15 control participants (7 males; median age 17years) were included in the study. Bowel wall T1 estimates in CD patients (median 1302ms) were significantly longer compared to control participants (median 1159ms) (p < 0.001). In CD patients, T1 estimates changed over time after treatment (p = 0.001), with largest reductions between baseline and 6-weeks (p < 0.001). T1 estimates correlated with inflammatory markers, including erythrocyte sedimentation rate (ρ = 0.35; p = 0.01), c-reactive protein level (ρ = 0.34; p = 0.02), and weighted Pediatric Crohn's Disease Activity Index (ρ = 0.39; p = 0.005). T1 estimates did not correlate with serum albumin (ρ = - 0.28; p = 0.051) and fecal calprotectin (ρ = 0.07; p = 0.63). Bowel wall T1 estimates are abnormally increased in newly diagnosed ileal CD patients and decrease in response to medical therapy.

1260-P: Gut Microbiome and Metabolic Activity in Type 1 Diabetes—An Analysis Based on the Presence of GADA

Background: Type 1 diabetes (T1D) progression is affected by the level of circulating glutamic acid decarboxylase antibody (GADA) , a main manifestation of islet autoimmunity. The gut microbiome and serum metabolites may contribute to islet autoimmunity in patients with T1D. Methods: We used radiobinding assay to measure GADA titers and identify the GADA+ ones (n=49) in 1T1D patients. The gut microbiome was assessed by 16S rRNA gene sequencing, and the serum metabolites were analysed with GC/MS. Results: T1D patients with and without GADA exhibited compositional and functional changes in the gut microbiome. Profiles in patients with GADA were distinct, with a significant increase in the abundances of Alistipes, Ruminococcus, Prevotella, Dialister, and marked depletion of Bacteroides, Bifidobacterium, Roseburia. For the untargeted serum metabolites, compared with those of GADA-, there were 54 significantly different metabolites with tryptophan metabolism: phenylalanine, and tyrosine and tryptophan biosynthesis decreased in patients with GADA. In addition, patients with GADA had elevated concentrations of Indole-3-acetic-acid, a marker of intestinal inflammation and epithelial damage. Co-occurrence network analysis revealed that gut microbiome disturbances affected tryptophan metabolism, suggesting that disturbed gut microbiome may mediate T1D immunotypes. Tryptophan metabolism may mediate inflammation in the pathogenesis and pathophysiology of T1D. Conclusion: These findings suggest that metabolites produced by the patients with GADA gut microbiota could cause damage to intestinal and systemic homeostasis and could be targeted for preventing the development of T1D. Disclosure T.Yue: None. X.Zheng: None. Z.Liu: None. Y.Ding: None. J.W.Wei: None. W.Xu: None. J.Weng: None. S.Luo: None. Funding the National Key r&amp;D Program (2017YFC1309600) the Anhui Provincial Natural science foundation (006212943003)

Protocol for a systematic review on routine use of antibiotics for infants less than 6 months of age with growth failure/faltering

IntroductionAntibiotics have been used as an adjunct in treating children with severe acute malnutrition 6–59 months of age; however, the data for infants less than 6 months are scarce. The...

Resilience or susceptibility to traumatic stress: Potential influence of the microbiome

Exposure to traumatic stress is a major risk factor for development of neuropsychiatric disorders in a sub-population of individuals, while others remain resilient. The mechanisms and contributing factors differentiating between these phenotypes are still unclear. We hypothesize that inter-individual differences in the microbial composition and function contribute to host resilience or susceptibility to stress-induced psychopathologies. The current study aimed to characterize gut microbial community before and after exposure to traumatic stress in an animal model of PTSD. Sprague-Dawley male rats were randomly divided into unstressed controls and experimental group subjected to Single Prolonged Stress (SPS). After 14 days, behavioral analyses were performed using Open Field, Social Interaction and Elevated Plus Maze tests. Based on the anxiety measures, the SPS group was further subdivided into resilient (SPS-R) and susceptible (SPS–S) cohorts. The animals were sacrificed after the last behavioral test and cecum, colon, hippocampus, and medial prefrontal cortex were dissected. Prior to SPS and immediately after Open Field test, fecal samples were collected from each rat for 16S V3–V4 ribosomal DNA sequencing, whereas urine samples were collected before SPS, 90 min into immobilization and on the day of sacrifice to measure epinephrine and norepinephrine levels. Analyses of the fecal microbiota revealed significant differences in microbial communities and in their predictive functionality among the groups before and after SPS stressors. Before SPS, the SPS-S subgroup harbored microbiota with an overall pro-inflammatory phenotype, whereas SPS-R subgroup had microbiota with an overall anti-inflammatory phenotype, with predictive functional pathways enriched in carbohydrate and lipid metabolism and decreased in amino acid metabolism and neurodegenerative diseases. After SPS, the gut microbial communities and their predictive functionality shifted especially in SPS cohorts, with volatility at the genus level correlating inversely with Anxiety Index. In line with the alterations seen in the gut microbiota, the levels of cecal short chain fatty acids were also altered, with SPS-S subgroup having significantly lower levels of acetate, valerate and caproate. The levels of acetate inversely correlated with Anxiety Index. Interestingly, urinary epinephrine and norepinephrine levels were also higher in the SPS-S subgroup at baseline and during stress, indicative of an altered sympathoadrenal stress axis. Finally, shorter colon (marker of intestinal inflammation) and a lower claudin-5 protein expression (marker for increased blood brain barrier permeability) were observed in the SPS-S subgroup. Taken together, our results suggest microbiota is a potential factor in predisposing subjects either to stress susceptibility or resilience. Moreover, SPS triggered significant shifts in the gut microbiota, their metabolites and brain permeability. These findings could lead to new therapeutic directions for PTSD possibly through the controlled manipulation of gut microbiota. It may enable early identification of individuals more likely to develop prolonged anxiogenic symptoms following traumatic stress.