Non-pharmacologic approaches to treatment of pediatric functional abdominal pain disorders.

Functional abdominal pain disorders (FAPDs) affect up to 25% of children in the United States. These disorders are more recently known as disorders of "brain-gut" interaction. The diagnosis is based on the ROME IV criteria, and requires the absence of an organic condition to explain the symptoms. Although these disorders are not completely understood, several factors have been involved in the pathophysiology including disordered gut motility, visceral hypersensitivity, allergies, anxiety/stress, gastrointestinal infection/inflammation, as well dysbiosis of the gut microbiome. The pharmacologic and non-pharmacologic treatments for FAPDs are directed to modifying these pathophysiologic mechanisms. This review aims to summarize the non-pharmacologic interventions used in the treatment of FAPDs including dietary modifications, manipulation of the gut microbiome (neutraceuticals, prebiotics, probiotics, synbiotics and fecal microbiota transplant) and psychological interventions that addresses the "brain" component of the brain-gut axis (cognitive behavioral therapy, hypnotherapy, breathing and relaxation techniques). In a survey conducted at a large academic pediatric gastroenterology center, 96% of patients with functional pain disorders reported using at least 1 complementary and alternative medicine treatment to ameliorate symptoms. The paucity of data supporting most of the therapies discussed in this review underscores the need for large randomized controlled trials to assess their efficacy and superiority compared to other treatments.

Probiotic-Derived Ecto-5'-Nucleotidase Produces Anti-Inflammatory Adenosine Metabolites in Treg-Deficient Scurfy Mice.

Probiotic Limosilactobacillus reuteri DSM 17938 (DSM 17938) prolongs the survival of Treg-deficient scurfy (SF) mice and reduces multiorgan inflammation by a process requiring adenosine receptor 2A (A2A) on T cells. We hypothesized that L. reuteri-derived ecto-5'-nucleotidase (ecto-5'NT) activity acts to generate adenosine, which may be a central mediator for L. reuteri protection in SF mice. We evaluated DSM 17938-5'NT activity and the associated adenosine and inosine levels in plasma, gut, and liver of SF mice. We examined orally fed DSM 17938, DSM 17938Δ5NT (with a deleted 5'NT gene), and DSM 32846 (BG-R46) (a naturally selected strain derived from DSM 17938). Results showed that DSM 17938 and BG-R46 produced adenosine while "exhausting" AMP, whereas DSM 17938∆5NT did not generate adenosine in culture. Plasma 5'NT activity was increased by DSM 17938 or BG-R46, but not by DSM 17938Δ5NT in SF mice. BG-R46 increased both adenosine and inosine levels in the cecum of SF mice. DSM 17938 increased adenosine levels, whereas BG-R46 increased inosine levels in the liver. DSM 17938Δ5NT did not significantly change the levels of adenosine or inosine in the GI tract or the liver of SF mice. Although regulatory CD73+CD8+ T cells were decreased in spleen and blood of SF mice, these regulatory T cells could be increased by orally feeding DSM 17938 or BG-R46, but not DSM 17938Δ5NT. In conclusion, probiotic-5'NT may be a central mediator of DSM 17938 protection against autoimmunity. Optimal 5'NT activity from various probiotic strains could be beneficial in treating Treg-associated immune disorders in humans.

Probiotic-derived ecto-5'-nucleotidase produces anti-inflammatory adenosine metabolites in Treg-deficient scurfy mice.

Probiotic Limosilactobacillus reuteri DSM 17938 (DSM 17938) prolonges the survival of Treg-deficient scurfy (SF) mice and reduces multiorgan inflammation by a process requiring adenosine receptor 2A (A 2A ) on T cells. We hypothesized that L. reuteri -derived ecto-5'-nucleotidase (ecto-5'NT) activity acts to generate adenosine, which may be a central mediator for L. reuteri protection in SF mice. We evaluated DSM 17938-5'NT activity and the associated adenosine and inosine levels in plasma, gut and liver of SF mice. We examined orally fed DSM 17938, DSM 17938Δ5NT (with a deleted 5'NT gene), and DSM 32846 (BG-R46) (a naturally selected strain derived from DSM 17938). Results showed that DSM 17938 and BG-R46 produced adenosine while "exhausting" AMP, whereas DSM 17938∆5NT did not generate adenosine in culture. Plasma 5'NT activity was increased by DSM 17938 or BG-R46, but not by DSM 17938Δ5NT in SF mice. BG-R46 increased both adenosine and inosine levels in the cecum of SF mice. DSM 17938 increased adenosine levels, whereas BG-R46 increased inosine levels in the liver. DSM 17938Δ5NT did not significantly change the levels of adenosine or inosine in the GI tract or the liver of SF mice. Although regulatory CD73 + CD8 + T cells were decreased in spleen and blood of SF mice, these regulatory T cells could be increased by orally feeding DSM 17938 or BG-R46, but not DSM 17938Δ5NT. In conclusion, probiotic-5'NT may be a central mediator of DSM 17938 protection against autoimmunity. Optimal 5'NT activity from various probiotic strains could be beneficial in treating Treg-associated immune disorders in humans.

Impact of probiotic Limosilactobacillus reuteri DSM 17938 on amino acid metabolism in the healthy newborn mouse.

We studied the effect of feeding a single probiotic Limosilactobacillus reuteri DSM 17938 (LR 17938) on the luminal and plasma levels of amino acids and their derivatives in the suckling newborn mouse, using gas chromatography and high-performance liquid chromatography. We found that LR 17938 increased the relative abundance of many amino acids and their derivatives in stool, while it simultaneously significantly reduced the plasma levels of three amino acids (serine, citrulline, and taurine). Many peptides and dipeptides were increased in stool and plasma, notably gamma-glutamyl derivatives of amino acids, following ingestion of the LR 17938. Gamma-glutamyl transformation of amino acids facilitates their absorption. LR 17938 significantly upregulated N-acetylated amino acids, the levels of which could be useful biomarkers in plasma and warrant further investigation. Specific fecal microbiota were associated with higher levels of fecal amino acids and their derivatives. Changes in luminal and circulating levels of amino acid derivatives, polyamines, and tryptophan metabolites may be mechanistically related to probiotic efficacy.

Rapunzel Syndrome Complicated by Escherichia coli Sepsis, Bowel Perforation, and Pancreatitis in an 11-year-old Malnourished Female.

The most common presenting symptoms of Rapunzel syndrome include abdominal pain (37%), nausea and vomiting (33.3%), obstruction (25.9%), and peritonitis (18.3%). Less commonly, patients may present with weight loss (7.4%) or intussusception (7.4%). Exceedingly rare complications of Rapunzel syndrome include gastric ulceration, obstructive jaundice, and acute pancreatitis as well as other malabsorptive-related complications including protein-losing enteropathy, iron deficiency, and megaloblastic anemia. This report details the case of an 11-year-old female with Rapunzel syndrome complicated by sepsis, a rare complication reported in only 2% of patients.

Health Equity and Social Determinants of Health in Pediatric Gastroenterology.

Social determinants of health (SDH) as outlined by Healthy People 2020 encompasses 5 key domains: economic, education, social and community context, health and health care, and neighborhood and built environment. This article emphasizes pediatric populations and some of the existing SDH and health care disparities seen in pediatric gastroenterology. We specifically review inflammatory bowel disease, endoscopy, bariatric surgery, and liver transplantation. We also examine the burgeoning role of telehealth that has become commonplace since the coronavirus disease 2019 era.

Recognizing a MIS-Chievous Cause of Acute Viral Gastroenteritis.

Historically, children evaluated for vomiting and diarrhea secondary to viral enteritis have symptoms lasting 2-4 days and respond to supportive care, including oral rehydration and anti-emetics if required. Recently, within a 14-day timespan, we encountered three children with severe diarrhea who rapidly became dehydrated and went into hypotensive shock. Although SARS-CoV-2 molecular tests were negative by nasopharyngeal swab, all were later found to have MIS-C. This small case series underscores features reported in previous larger studies and emphasizes the rapid clinical evolution of this condition. We highlight the importance of early recognition of cardinal laboratory findings characteristic of MIS-C (i.e., lymphopenia, markedly elevated acute phase reactants, and hypoalbuminemia). We also show serologic evidence that the pathophysiological mechanism of SARS-CoV-2 related diarrhea may differ from other causes of dehydrating vomiting and diarrhea, with no serologic evidence of villus cell injury.

State of the art vaccination strategies as primary prevention to reduce incidence of gastrointestinal cancers.

Immunizations have influenced the epidemiology of numerous gastrointestinal cancers. Human papillomavirus (HPV) is a common sexually transmitted infection (STI). Although most infections are transient and asymptomatic, persistent infections with oncogenic strains of HPV can progress to cervical, anal, penile, vaginal, vulvar, and oropharyngeal cancers. The introduction of HPV vaccinations has drastically reduced incidences of HPV-vaccine related infections and HPV related cervical cancers. The vaccine has proven to be safe and effective however, HPV vaccination rates have yet to reach target goals in the U.S. and many countries worldwide have not incorporated the vaccine into national immunization programs. The first successful nationwide vaccination program was employed against hepatitis B virus (HBV) in Taiwan in 1984 and demonstrated a statistically significant decrease in the incidence of hepatocellular carcinoma (HCC) in the 6 to 10 years after implementation of universal HBV vaccinations in infants. Twenty-year follow-up studies have continued to demonstrate statistically significant decreased rates of HBV related HCC among vaccinated populations. Despite the successful decrease in incidence of HBV-related HCC, efforts to create an effective prophylactic vaccination against hepatitis C virus (HCV) to prevent chronic HCV infection and its associated morbidity, including HCV-related HCC, have to date been unsuccessful.

The Perceived Ostomy Educational Needs of Pediatric Patients With Inflammatory Bowel Disease and Their Caregivers.

Inflammatory bowel disease (IBD) is a chronic disease causing inflammation of the gastrointestinal tract. Some patients require ostomy surgery to optimize their health. This study assessed perceived medical and psychosocial educational needs related to ostomy surgery in pediatric patients with IBD. This mixed-methods study included qualitative interviews of pediatric patients and caregivers with demographic/medical variables obtained from medical records. Participants (n = 8) had an average age of 15.62 years (standard deviation = 2.97). Mean length of diagnosis was 4.5 years (standard deviation = 3.6 years). Interviews were transcribed and coded. Qualitative coding of narratives identified main codes of Ostomy Surgery, Preoperative Concerns, Postoperative Concerns, Education Preferences, and Social Concerns, with various subcodes. Codes captured unfamiliarity with the ostomies, preferences for education from a medical provider, and psychosocial concerns. Results suggest pediatric patients with IBD have limited understanding of ostomies and limited insight into educational preferences. These findings highlight the importance of developmentally appropriate information for accessible ostomy education.