Increased number of children in households may protect against inflammatory bowel disease.

BACKGROUND: The increasing incidence of inflammatory bowel disease (IBD: Crohn's disease and ulcerative colitis) around the world has coincided with a wide array of environmental and epidemiologic changes. The relationship between IBD incidence and household or family size decline, however, has not been examined before. Our background epidemiological analyses suggested an inverse association between household size and IBD incidence. We aimed to examine this further in a murine model. METHODS: We designed a unique two-generation cohousing model of family size and IBD susceptibility in C57BL/6J mice. Serial fecal microbiomes during cohousing were examined by high-throughput 16S rRNA sequencing. After cohousing for 10 days, mice were exposed to dextran sulfate sodium (DSS) to induce acute colitis. Body weight as a significant correlate of colitis severity was measured. RESULTS: Mice in a large household arrangement demonstrated less weight loss than mice in the small household arrangement in the DSS model. Age- and housing-dependent microbiome shifts were found. CONCLUSIONS: Larger households may be protective against intestinal inflammation through intergenerational microbiome modulation. Our observations may set the foundation for age-dependent, microbiome-directed future prevention against IBD. IMPACT: Epidemiological analyses in this study suggested that IBD incidence may inversely correlate with household size (an indicator of family size/children per family), which has not been examined before. A uniquely designed two-generation cohousing model of family size and IBD susceptibility in mice supported our epidemiologic observations. Microbiome changes in our cohousing model may set the foundation for age-dependent, microbiome-directed prevention against IBD.

Racial and Ethnic Variation in Presentation, Diagnosis, Treatment, and Outcome of Pediatric Crohn Disease: A Single Center Study.

OBJECTIVES: Disparities in health care for racial/ethnic minority children in the United States who are burdened by pediatric Crohn's disease (PCD) are not well understood. METHODS: A retrospective review of the Texas Children's Hospital ImproveCareNow database from 2007 to 2015 was performed. CD patients with a minimum of 2-year follow-up were included if the onset of symptoms attributable to inflammatory bowel disease was clearly documented. We primarily aimed to identify race and ethnicity associations in diagnostic delay, presentation, treatment, and 2-year outcomes. We also examined early versus late diagnosis (ie, over 6 months from disease onset) associations with these variables unrelated to race/ethnicity. RESULTS: One hundred and sixty-six PCD patients [57.8% non-Hispanic White (NH-White), 18.1% African American (AA), and 15.7% Hispanic] met selection criteria. Time to diagnosis was shorter in Hispanic patients ( P < 0.01) and they were older at diagnosis than NH-White patients ( P = 0.0164). AA patients (33%, P < 0.01) and Hispanic patients (35%, P < 0.05) had lower rates of granuloma detection than NH-White patients (63%). AA patients had lower rates of steroid-free remission (SFR) at 2 years than NH-White patients ( P < 0.05). Higher ESR and lower hemoglobin levels were associated with early diagnosis ( P < 0.01). Early diagnosis was associated with higher rates of surgery within 2 years of diagnosis ( P < 0.05). Diagnostic fecal calprotectin levels inversely associated with SFR at 2 years ( P < 0.05). Early use of biologics positively, and early use of corticosteroids negatively correlated with 2-year SFR ( P < 0.05). CONCLUSIONS: Race and ethnicity may influence the diagnosis, treatment, and outcomes of PCD. This recognition presents a nidus toward establishing equity in PCD care.

Maternal Lactobacillus reuteri supplementation shifts the intestinal microbiome in mice and provides protection from experimental colitis in female offspring.

The purpose of our experiment was to explore how stochastic (inter-individual variation) gut microbiome composition may link to inflammatory bowel disease (IBD) susceptibility and guide the development of a perinatal preventative probiotic. Dextran sodium sulfate (DSS) was introduced to C57BL/BJ mice to induce acute colitis as a model of IBD. Potentially protective bacteria were identified using a discovery-validation cohort approach toward stochastic DSS susceptibility. Lactobacilli (two different cocktails of L. reuteri and L. johnsonii strains) or control media were supplemented by mouth to dams prior to delivery and during lactation (i.e., perinatal probiotic). The pups were evaluated for DSS susceptibility at young adulthood. Fecal Lactobacillus was increased in the DSS-resistant mice in both the discovery and validation cohorts. Maternal supplementation of female offspring with an L. reuteri cocktail (strains 6798-1, 6798-jm, and 6798-cm) induced progressive microbiome separation and protection against colitis by young adulthood. Maternal supplementation of L. reuteri could confer protection against DSS colitis in young adult female mice. This work is the first to exploit stochastic mammalian microbiome variation to guide microbial therapeutic identification. Our findings underscore neonatal microbiome plasticity and set the stage for the potential development of perinatally deliverable protective probiotics against human IBD.

Microbiome Responses to Vancomycin Treatment in a Child With Primary Sclerosing Cholangitis and Ulcerative Colitis.

The therapeutic effects of off-label oral vancomycin in pediatric and adult primary sclerosing cholangitis (PSC)-inflammatory bowel disease, more commonly PSC-ulcerative colitis (UC), indicate the translational relevance of disease-associated microbiome findings. This is the first report on longitudinal salivary and fecal microbiome changes in a pediatric PSC-UC patient over the first 90 days of vancomycin therapy. Increase in bacterial diversity and abundance changes in Fusobacterium, Haemophilus, and Neisseria were observed. Our findings highlight the importance of longitudinal microbiome sampling in PSC-UC and serve as a nidus for larger-scale observations toward advancing microbial therapeutics for PSC.

Durable Clinical and Biochemical but Not Endoscopic Remission in Pediatric Crohn's Disease on Specific Carbohydrate Diet Monotherapy.

The specific carbohydrate diet (SCD) is an exclusion diet that has gained increasing public attention as a treatment option for inflammatory bowel diseases (IBDs: Crohn's Disease (CD) and Ulcerative Colitis (UC)). Studies have demonstrated SCD leads to clinical and biochemical remission. Additional observations had controversial results when mucosal healing, or endoscopic remission was assessed in pediatric CD patients on partial SCD therapy, or SCD as adjunct treatment. There is currently a lack of mucosa-based assessments for pediatric IBD patients on SCD monotherapy. We report three pediatric CD patients who achieved clinical remission on SCD monotherapy, but failed to demonstrate complete mucosal healing with a minimum of one year follow up. This case report highlights that SCD monotherapy in male pediatric CD patients can sustain durable clinical and biochemical remission, but not full mucosal healing.

Diagnostic delay and colectomy risk in pediatric ulcerative colitis.

BACKGROUND/PURPOSE: Diagnostic delay or time to diagnosis, and its relationship with colectomy risk has been studied in adult Inflammatory Bowel Disease (IBD), but rarely in pediatric IBD (PIBD), especially pediatric ulcerative colitis (P-UC), which often has a more severe course than adult UC. This study compared the relationship between diagnostic delay and colectomy in P-UC. METHODS: The medical records of P-UC patients, ages <18 years, diagnosed at Texas Children's Hospital from 2012 to 2018 were examined. We identified 106 P-UC patients, where the onset of symptoms of IBD (i.e. fever, diarrhea, blood in stool, weight loss, abdominal pain) could be clearly identified. RESULTS: Twenty (20 = 18.9%) patients progressed to colectomy, and 86 did not. There was no significant difference in diagnostic delay between the patients undergoing colectomy with UC (C-UC) and those with no colectomy (NC-UC) (p = 0.2192). The median (C-UC = 7.1 weeks; NC-UC = 11.9 weeks) and mean (C-UC = 16.5 weeks±4.7; NC-UC = 20.1 ±â€¯2.6) diagnostic delay actually tended to be shorter in C-UC compared to NC-UC. Fecal calprotectin levels were significantly higher (p = 0.0228) in C-UC than NC-UC patients at diagnosis. CONCLUSIONS: Shorter time to diagnosis may reflect disease severity at the time of disease onset and also a more aggressive subsequent course of P-UC. The significantly higher level of fecal calprotectin in the C-UC patients at diagnosis provided biologic/biochemical support for our conclusion. LEVELS OF EVIDENCE: Prognosis study, Level III evidence.

Carbohydrate Monotony as Protection and Treatment for Inflammatory Bowel Disease.

The nutritional developmental origins of inflammatory bowel disease[s] (IBDs: Crohn's disease or Crohn disease [CD] and ulcerative colitis [UC]) and their diet-based treatments continue to receive increasing attention. There is growing evidence for the success of nutrition-based treatments, such as exclusive enteral nutrition [EEN] and the specific carbohydrate diet [SCD], in both paediatric and adult patients. Beyond these two dietary interventions, symptomatic benefit in IBD has also been shown from a gluten-free diet [GFD] and paleolithic diet [PALEO], among others. These nutritional therapies may point to critical factors in not only the pathology, but also the pathogenesis of the disease group. It is difficult, however, to discern a common element within the large number of diet-based causation theories [e.g. emulsifiers, processed foods, refrigeration, increased total fat intake, low fibre intake, carbohydrate dominant food, etc.] and the varied dietary treatments of IBD. This Viewpoint article highlights that carbohydrate variation links diet-based causation theories, and that carbohydrate monotony or persistence is the commonly shared characteristic of diet-based IBD therapy. Further research directed towards carbohydrate monotony may critically advance the prevention and treatment of these highly morbid conditions.

Weight loss is a sufficient and economical single outcome measure of murine dextran sulfate sodium colitis.

Inflammatory bowel diseases (IBD: Crohn's disease and ulcerative colitis) are becoming common around the world without a cure. Animal models of colitis have become instrumental in IBD research. The dextran sulfate sodium (DSS) induced murine colitis model is likely the most utilized due to its simplicity and reproducibility with over 4000 publications on PubMed, where weight loss is the most commonly used and reliable positive correlate. We predicted at current state of art, that the DSS colitis model can be optimized by using weight loss as a single cost-saving outcome measure. Twenty recent and consecutive publications using the DSS model in PubMed were selected for review. Guarded cost estimations for additional outcome measures of colitis beyond weight loss were performed. In all manuscripts (100%), weight loss corroborated the conclusions. Average excess cost for examining additional measures of colitis was approximately $6700 per publication. Two studies (10.5%) were estimated to have spent over $20,000 in excess. Additional measures of colitis either supported the final conclusions found with weight loss, or lead to indeterminate results. Potential annual savings from following our guidance were calculated to be over $60,000 for and IBD lab. We conclude that weight loss is a sufficient, objective, and economical outcome measure of DSS-induced colitis in mice.