Malabsorption Of Nutrients Research Articles

Effect of high-dose multivitamin supplements on alanine aminotransferase elevations among adults living with HIV on antiretroviral therapy in Tanzania.

HIV infection can cause malabsorption and rapid utilization of nutrients. A randomized trial of multivitamin supplementation among people living with HIV/AIDS (PLWHA) initiating antiretroviral therapy (ART) in Tanzania was stopped early due to increased alanine aminotransferase (ALT) concentrations in the multiple recommended dietary allowances (RDA) multivitamin group. We conducted detailed analysis to assess the effect of multivitamins on ALT elevations and evaluate whether subgroups of PLWHA have greater hepatotoxicity risks associated with the use of high-dose multivitamins. We utilized data from a randomized, double-blind trial conducted in 2006-2009 that assessed the effect of high-dose multivitamins that contained vitamin B complex, vitamin C, and vitamin E at multiple RDA as compared to standard-dose multivitamins containing single RDAs among adults initiating ART in Tanzania. We evaluated the effect of high-dose multivitamins on incident mild/moderate ALT elevations > 40 IU/L, persistent ALT elevations > 40 IU/L (2 + clinic visits), and severe ALT elevations > 200IU/L using Cox proportional hazard models. We then evaluated effect modification by patient characteristics to determine if subgroups of PLWHA experienced different magnitudes of risk for ALT elevations associated with high-dose multivitamins. High-dose multivitamins increased the risk of incident mild/moderate ALT elevations > 40 IU/mL as compared to standard-dose multivitamins (hazard ratio (HR): 1.41; 95%CI: 1.26,1.58) as well as incident sustained mild/moderate ALT elevations (HR: 1.19; 95%CI: 1.04,1.36), but there was no overall effect on severe ALT elevations (HR: 1.44; 95% CI: 0.91,2.28). There was no evidence that the effect of high-dose multivitamins on any or sustained mild/moderate ALT elevations was modified by any patient characteristic. However, CD4 T-cell count was found to modify the effect of high-dose multivitamins on severe ALT elevations (p-value for interaction:0.01). Among participants with a baseline CD4 T-cell count ≤ 100 cells/µL, individuals receiving high-dose multivitamins had 3.74 times (95%CI: 1.52-9.17) the risk of incident severe ALT elevations compared to standard-dose multivitamins, while participants with CD4 T-cell counts > 100 cells/µL, appeared to have no effect of high-dose multivitamins on severe ALT elevations (HR:0.92; 95% CI: 0.50,1.67). High-dose RDA multivitamin supplementation increased the incidence of any mild to moderate ALT elevations among adults starting ART in Tanzania and the magnitude of the risk does not appear to differ by patient characteristics. However, immunocompromised PLWHA with CD4 T-cell counts < 100 cells/µL may experience greater risk of severe ALT elevations associated with the use of high-dose multivitamins. Although the study findings offer significant insights, it is essential to take into account limitations imposed by newer cART regimes.

TREM2 macrophages mediate the beneficial effects of bariatric surgery against MASH.

For patients with obesity and metabolic syndrome, bariatric procedures such as vertical sleeve gastrectomy (VSG) have a clear benefit in ameliorating metabolic dysfunction-associated steatohepatitis (MASH). While the effects of bariatric surgeries have been mainly attributed to nutrient restriction and malabsorption, whether immuno-modulatory mechanisms are involved remains unclear. Using murine models, we report that VSG ameliorates MASH progression in a weight loss-independent manner. Single-cell RNA sequencing revealed that hepatic lipid-associated macrophages (LAMs) expressing the triggering receptor expressed on myeloid cells 2 (TREM2) repress inflammation and increase their lysosomal activity in response to VSG. Remarkably, TREM2 deficiency in mice ablates the reparative effects of VSG, suggesting that TREM2 is required for MASH resolution. Mechanistically, TREM2 prevents the inflammatory activation of macrophages and is required for their efferocytic function. Overall, our findings indicate that bariatric surgery improves MASH through a reparative process driven by TREM2+ macrophages, providing insights into the mechanisms of disease reversal that may result in new therapies and improved surgical interventions.

The lipopolysaccharide structure affects the detoxifying ability of intestinal alkaline phosphatases

Lipopolysaccharide (LPS) is one of the most potent mediators of inflammation. In swine husbandry, weaning is associated with LPS-induced intestinal inflammation, resulting in decreased growth rates due to malabsorption of nutrients by the inflamed gut. A potential strategy to treat LPS-mediated disease is administering intestinal alkaline phosphatase (IAP). The latter can detoxify lipid A, the toxic component of LPS, by removal of phosphate groups. Currently, 183 LPS O-serotypes from E. coli have been described, however, comparative experiments to elucidate functional differences between LPS serotypes are scarce. In addition, these functional differences might affect the efficacy of LPS detoxifying enzymes. Here, we evaluated the ability of four LPS serotypes (O26:B6, O55:B5, O111:B4 and O127:B8) derived from Escherichia coli to trigger the secretion of pro-inflammatory cytokines by porcine PBMCs. We also tested the ability of three commercially available IAPs to detoxify these LPS serotypes. The results show that LPS serotypes differ in their ability to trigger cytokine secretion by immune cells, especially at lower concentrations. Moreover, IAPs displayed a different detoxification efficiency of the tested serotypes. Together, this study sheds light on the impact of LPS structure on the detoxification by IAPs. Further research is however needed to elucidate the LPS serotype-specific effects and their implications for the development of novel treatment options to alleviate LPS-induced gut inflammation in weaned piglets.

CROHN'S DISEASE AND OSTEOPOROSIS: RISK FACTORS, DIAGNOSIS AND CLINICAL TREATMENT

Crohn's disease (CD) is a chronic inflammatory bowel disease that affects any part of the gastrointestinal tract. Osteoporosis, in turn, is a skeletal disease characterized by decreased bone mass and deterioration of bone microarchitecture, increasing the risk of fractures. The association between these two diseases has been increasingly investigated, with evidence suggesting that patients with CD are at increased risk of developing osteoporosis. This comorbidity can be attributed to several factors, including corticosteroid use, nutrient malabsorption, chronic inflammation, and hormonal dysfunction. Objective: The objective of this systematic review was to identify and synthesize the available scientific evidence on the relationship between Crohn's disease and osteoporosis, focusing on risk factors, diagnosis, and clinical treatment. Methodology: A systematic review of the literature was performed, following the recommendations of the PRISMA statement. The PubMed, Scielo and Web of Science databases were searched using the following descriptors: “Crohn’s disease”, “Osteoporosis”, “Risk factors”, “Diagnosis” and “Treatment”. Original articles published in the last 10 years, in Portuguese or English, that investigated the association between CD and osteoporosis in adults were included. Case studies, narrative reviews and articles that did not address the relationship between the two diseases were excluded. Results: The results of the review demonstrated that osteoporosis is a frequent complication in patients with CD. Several risk factors were identified, including the use of corticosteroids, malabsorption of calcium and vitamin D, chronic inflammation and hormonal dysfunction. The diagnosis of osteoporosis in patients with CD can be challenging due to the presence of other factors that can affect bone mineral density, such as malnutrition and immobilization. Treatment of osteoporosis in patients with CD should be individualized and may include pharmacological and non-pharmacological measures, such as calcium and vitamin D supplementation, regular physical activity, and reduced tobacco and alcohol consumption. Conclusion: Crohn's disease represents a significant risk factor for the development of osteoporosis. The association between these two diseases is complex and multifactorial, involving several pathogenic mechanisms. Early diagnosis and appropriate treatment of osteoporosis in patients with CD are essential to prevent fractures and improve the quality of life of these patients. It is essential that health professionals are aware of this comorbidity and offer integrated clinical management for these patients.

Association of gut microbiota with lactose intolerance and coeliac disease: a two-sample Mendelian randomization study.

Lactose intolerance and coeliac disease are common clinical nutrient malabsorption disorders, with an unclear pathogenesis and limited therapeutic options. It is widely believed that the gut microbiota plays an important role in many digestive disorders, but its role in lactose intolerance and coeliac disease is not yet clear. This study aimed to investigate the correlation between gut microbiota and lactose intolerance and coeliac disease. This study utilized the genome-wide association study database to investigate the association between gut microbiota and lactose intolerance and coeliac disease using Mendelian randomization (MR). The robustness of our findings was confirmed through subsequent analyses including Cochrane's Q statistic, MR-Egger Intercept Regression, MR-PRESSO Global Test and Leave-one-out methods. By employing the inverse variance weighted method, we identified that family Veillonellaceae, genus Oxalobacter and Senegalimassilia were protective against lactose intolerance, whereas genus Anaerotruncus, Eubacterium rectale group and Ruminococcus2 were found to be risk factors for lactose intolerance. Regarding coeliac disease, class Bacilli and Gammaproteobacteria, family FamilyXIII and Veillonellaceae, genus Eisenbergiella, Lachnoclostridium, RuminococcaceaeUCG014 and Ruminococcus2 were identified as protective factors, while class Betaproteobacteria, genus Eubacterium xylanophilum group and Blautia were risk factors. Furthermore, reverse the MR analysis did not reveal any evidence of a causal relationship between lactose intolerance or coeliac disease and the bacteria identified in our study. This study provides novel insights into exploring the role of gut microbiota in lactose intolerance and coeliac disease; however, further experiments investigations are required to elucidate the specific underlying mechanisms.

Gastrointestinal and Hepatobiliary Manifestations Associated with Untreated Celiac Disease in Adults and Children: A Narrative Overview.

Celiac disease (CeD) is a chronic inflammatory disease of the small intestine, produced by ingesting dietary gluten products in susceptible people. Gluten causes an impairment of the mucosal surface and, consequently, an abnormal absorption of nutrients. Although malabsorption of essential nutrients is a major risk factor for various CeD-associated morbidities, genetic, immunological, and environmental factors also play an important role. The clinical presentation of CeD widely varies and can range from asymptomatic to full-blown symptoms due to the multi-system nature of CeD. The typical gastrointestinal (GI) manifestations of CeD include abdominal pain, diarrhea, bloating, and weight loss, but several hepatobiliary manifestations and a poor nutritional status have also been described. Currently, a gluten-free diet (GFD) is the only current evidence-based treatment that leads to the complete recovery of mucosal damage and the reversibility of its progression. Conversely, undiagnosed CeD might have severe consequences in children as well as in adult patients. This narrative overview aims to characterize the GI and hepatobiliary manifestations, nutritional deficiencies, and delayed pediatric development associated with unrecognized CeD in order to identify it promptly. Moreover, the role of GFD and how it could prevent long-term complications of CeD are described.

Dysregulated serum concentrations of fat-soluble vitamins in dogs with chronic enteropathy.

In inflammatory bowel disease (IBD) of humans, nutrient malabsorption can result in fat-soluble vitamin deficiency, especially of vitamin D. In veterinary species, decreased concentrations of vitamin D are relatively common in dogs with chronic enteropathy (CE), but data on the status of other fat-soluble vitamins (FSVs) is lacking. Determine the serum concentrations of retinol, vitamin D, and α-tocopherol in dogs with CE compared with healthy dogs and compare clinical, clinicopathologic variables between CE and healthy dogs to detect associations with decreased FSVs concentrations. Eighteen client-owned dogs with CE and 33 healthy dogs. Serum 25-hydroxyvitamin D (25[OH]D), serum retinol and α-tocopherol concentrations were compared between groups. Correlations and multiple regression modeling were used to examine the relationship between serum 25(OH)D, retinol, and α-tocopherol concentrations and clinical and clinicopathological variables. Dogs with low serum albumin concentrations were more likely to have lower 25(OH)D concentrations than dogs with normal serum albumin concentration. Dogs with CE had higher serum concentrations of retinol, and variable α-tocopherol concentrations. The cause of these dysregulated vitamin concentrations is unclear and requires further study. Dogs with severe forms of CE should be monitored for decreased concentrations of 25(OH)D. Additional studies are needed to evaluate the clinical relevance and the possible benefit of vitamin D supplementation in these patients.

Acrodermatitis Enteropathica Following a Pull-Through Procedure

Abstract Introduction: Acrodermatitis Enteropathica is a rare condition traditionally expressed by perioral or acral dermatitis, diarrhea, and alopecia. Acrodermatitis Enteropathica can be inherited or acquired, with the acquired form linked to zinc deficiency. The pull-through procedure is a method used to treat Hirschsprung’s disease, a condition in which the large intestine is missing nerve cells that make it difficult to pass stool, which can lead to obstruction and absorption issues. Complications of pull-through procedures have been associated with bowel obstruction and malabsorption of essential nutrients, including zinc. Case Report: We present a 16-month-old male who developed perioral dermatitis, well-demarcated erythematous plaques, and alopecia after a pull-through procedure related to Hirschsprung’s disease. Discussion: Acrodermatitis Enteropathica can present with various cutaneous lesions, and dermatologists should be familiar with the differing morphologies. In this paper, we encourage dermatologists to consider Acrodermatitis Enteropathica as a differential diagnosis for patients who develop cutaneous lesions following pull-through procedures. Keywords: Acrodermatitis Enteropathica, Hirschsprung’s Disease, zinc deficiency, case report

Recent advances in fecal microbiota transplantation for Clostridium difficile infection-associated diarrhea after kidney transplantation

Kidney transplantation is considered to be the best treatment for end-stage renal disease. To reduce the incidence of rejection and improve the survival of recipients and kidney grafts, kidney transplant recipients must take immunosuppressive agents, and some patients require them for the rest of their lifetime. These treatment regimens can result in susceptibility to opportunistic infections and disrupt the intestinal microbiota, thereby leading to diarrhea, which causes water and electrolyte metabolism disorder, nutrient malabsorption, and instability in the blood concentrations of the immunosuppressive agents. Fluctuating blood concentration levels of these agents necessitate frequent laboratory monitoring and dose adjustments to avoid poor adherence and increase the risk of graft rejection. Furthermore, severe diarrhea can cause kidney transplant failure or death. Clostridium difficile infection (CDI) is the leading cause of diarrhea after renal transplantation. Traditional antibiotics can kill C. difficile; however, spores can remain in the gut. Disruption of the intestinal flora caused by antibiotherapy increases the risk of developing recurrent CDI (rCDI). Fecal microbiota transplantation (FMT) has been proven to be a safe and effective treatment for CDI and is recommended for rCDI owing to its convenient material acquisition method, high efficacy, and low incidence of adverse reactions. This review summarizes the recent progress in FMT for CDI-associated diarrhea after renal transplantation.

Are Infants and Children at Risk of Adverse Health Effects from Dietary Deoxynivalenol Exposure? An Integrative Review.

Deoxynivalenol (DON) is a foodborne mycotoxin produced by Fusarium molds that commonly infect cereal grains. It is a potent protein synthesis inhibitor that can significantly impact humans' gastrointestinal, immune, and nervous systems and can alter the microbiome landscape. Low-dose, chronic exposure to DON has been found to stimulate the immune system, inhibit protein synthesis, and cause appetite suppression, potentially leading to growth failure in children. At higher doses, DON has been shown to cause immune suppression, nausea, vomiting, abdominal pain, headache, diarrhea, gastroenteritis, the malabsorption of nutrients, intestinal hemorrhaging, dizziness, and fever. A provisional maximum tolerable daily intake (PMTDI) limit of 1 µg/kg/body weight has been established to protect humans, underscoring the potential health risks associated with DON intake. While the adverse effects of dietary DON exposure have been established, healthcare communities have not adequately investigated or addressed this threat to child health, possibly due to the assumption that current regulatory exposure limits protect the public appropriately. This integrative review investigated whether current dietary DON exposure rates in infants and children regularly exceed PMTDI limits, placing them at risk of negative health effects. On a global scale, the routine contamination of cereal grains, bakery products, pasta, and human milk with DON could lead to intake levels above PMTDI limits. Furthermore, evidence suggests that other food commodities, such as soy, coffee, tea, dried spices, nuts, certain seed oils, animal milk, and various water reservoirs, can be intermittently contaminated, further amplifying the scope of the issue. Better mitigation strategies and global measures are needed to safeguard vulnerable youth from this harmful toxicant.

Post-operative Ultrashort Bowel Syndrome in a Term Neonate: One-year Follow-up

Ultrashort bowel syndrome occurs when the length of the small bowel is below 10–25 cm, or 10% of that expected for age. It is a rare occurrence in neonates; however, when it occurs, it results in high morbidity and mortality. Surviving newborns face a significant detriment in growth and development due to malabsorption of nutrients. A multidisciplinary approach with aggressive parenteral nutrition is the mainstay of management. Our case presented at 20 days of life, with malrotation and midgut volvulus resulting in post-surgical ultrashort bowel syndrome. In spite of being left with only 20 cm of short bowel, the infant survived on conservative management and is thriving well; the infant has been off parenteral nutrition completely since 11 months of age.

Malnutrition in sickle cell anemia: Prevalence, impact, and interventions: A Review.

Sickle Cell Anemia (SCA) is a hereditary hemoglobinopathy characterized by chronic hemolytic anemia, vaso-occlusive events, and a wide range of clinical complications. Malnutrition, often an underexplored aspect of this complex condition, plays a critical role in disease management and overall patient well-being. This publication provides a comprehensive review of the prevalence, impact, and interventions related to malnutrition in individuals with SCA. A thorough literature review reveals the multifaceted challenges faced by SCA patients in maintaining adequate nutrition. The pathophysiology of SCA, involving chronic inflammation, oxidative stress, and hypermetabolism, contributes to increased nutritional requirements and altered dietary patterns. Factors such as reduced appetite, nutrient malabsorption, dietary restrictions, and socioeconomic disparities further exacerbate the risk of malnutrition. Malnutrition is a prevalent issue among individuals with SCA, affecting patients of different age groups and disease severities. Nutritional deficiencies, including vitamins, minerals, and essential nutrients, are common in this population. The impact of malnutrition on disease outcomes is significant, with associations between nutrient status and complications such as pain crises, infections, and impaired quality of life. This paper also reviews nutritional interventions aimed at addressing malnutrition in SCA patients. While dietary counseling, supplementation, and personalized nutrition plans have shown promise in improving nutritional status, challenges such as patient adherence and access to healthcare must be addressed to optimize their effectiveness.

Synergistic Effect of Postbiotic Yeast ABB C22® on Gut Inflammation, Barrier Function, and Protection from Rotavirus Infection in In Vitro Models

Diarrhoea is a serious cause of mortality worldwide that can lead to dehydration, gut barrier function impairment, nutrient malabsorption, and alterations of the gut microbiota (dysbiosis). The current solutions for its management, such as oral rehydration salts (ORS), inhibitors of gut motility, antibiotics, and living probiotics, only partially counteract the mechanisms of the disease and do not provide a full coverage of the problem. The potential risks of the use of living probiotic strains, particularly in immunocompromised patients, can be eliminated with the use of tyndallized (heat-killed) postbiotic bacteria and yeast. ABB C22® is a postbiotic combination of three tyndallized yeasts, namely Saccharomyces boulardii, Saccharomyces cerevisiae, and Kluyveromyces marxianus. To assess the action of the postbiotic combination on diarrhoea, immune and gut epithelial cell signalling assays, the gut barrier formation assay, and the rotavirus gene expression assay were performed. ABB C22® showed a strong anti-inflammatory effect, an induction of the build-up of the gut epithelium, and a degree of protection against rotavirus infection. These experimental studies support the use of the postbiotic ABB C22® as a solution for the management of diarrhoea and gastrointestinal conditions, alone or in combination with existing but incomplete treatments.

The Impacts of the Low-FODMAP Diet on the Management of Irritable Bowel Syndrome Symptoms: Possibilities, Feasibility, and Alternatives

Irritable bowel syndrome (IBS) is a common gastrointestinal (GI) condition characterized by a myriad of GI symptoms (e.g., diarrhea, nutrient malabsorption) that vary in severity. Due to its complex and individual nature, there is no known cure for IBS, but many diets have been assessed for their viability in managing symptoms. The low-FODMAP diet has recently been investigated for its potential benefits for IBS patients. FODMAPs, or Fermentable Oligosaccharides, Disaccharides, Monosaccharides, and Polyols are short- and medium-chain carbohydrates that are poorly absorbed in the small intestine and are prone to absorb water and ferment in the colon. Consumption of these FODMAPs correlates with increasing severity of IBS symptoms. The purpose of this randomized controlled trial systematic review was to compile various evidence-based dietary recommendations for the low-FODMAP diet for adult patients suffering from IBS from randomized controlled and clinical trials. The possibilities, feasibilities, and potential alternatives are proposed to determine if there is sufficient evidence to recommend the low-FODMAP diet for this patient population. Over 1,000 studies were screened and 6 were reviewed to determine the benefits of this diet. It was found that the low-FODMAP diet has demonstrated efficacy in delivering IBS symptom relief by changing patients’ metabolomes, microbiomes, and physiology. Specifically, this diet showed a greater overall decrease in abdominal pain, bloating, stool consistency, frequency, and urgency. Greater diversity of actinobacteria was found in the stool samples of these patients. Nociceptive neurons were also shown to be less sensitive and GI gas production was also markedly decreased. Despite these benefits, the low-FODMAP diet is more recommended for acute flare-ups due to its difficult adherence and attrition. Instead, we conclude that the balanced Mediterranean diet contains aspects of the traditional Mediterranean and low-FODMAP diet that can relieve IBS symptoms for daily life, while the low-FODMAP diet can be an effective treatment to ameliorate conditions when severe symptoms are experienced.

Obeticholic acid attenuates the intestinal barrier disruption in a rat model of short bowel syndrome

BackgroundShort bowel syndrome (SBS) features nutrients malabsorption and impaired intestinal barrier. Patients with SBS are prone to sepsis, intestinal flora dysbiosis and intestinal failure associated liver disease. Protecting intestinal barrier and preventing complications are potential strategies for SBS treatment. This study aims to investigate the effects of farnesoid X receptor (FXR) agonist, obeticholic acid (OCA), have on intestinal barrier and ecological environment in SBS. Methods and resultsThrough testing the small intestine and serum samples of patients with SBS, impaired intestinal barrier was verified, as evidenced by reduced expressions of intestinal tight junction proteins (TJPs), increased levels of apoptosis and epithelial cell damage. The intestinal expressions of FXR and related downstream molecules were decreased in SBS patients. Then, global FXR activator OCA was used to further dissect the potential role of the FXR in a rat model of SBS. Low expressions of FXR-related molecules were observed on the small intestine of SBS rats, along with increased proinflammatory factors and damaged barrier function. Furthermore, SBS rats possessed significantly decreased body weight and elevated death rate. Supplementation with OCA mitigated the damaged intestinal barrier and increased proinflammatory factors in SBS rats, accompanied by activated FXR-related molecules. Using 16S rDNA sequencing, the regulatory role of OCA on gut microbiota in SBS rats was witnessed. LPS stimulation to Caco-2 cells induced apoptosis and overexpression of proinflammatory factors in vitro. OCA incubation of LPS-pretreated Caco-2 cells activated FXR-related molecules, increased the expressions of TJPs, ameliorated apoptosis and inhibited overexpression of proinflammatory factors. ConclusionsOCA supplementation could effectively ameliorate the intestinal barrier disruption and inhibit overexpression of proinflammatory factors in a rat model of SBS and LPS-pretreated Caco-2 cells. As a selective activator of FXR, OCA might realize its protective function through FXR activation.

Risk of Gluten Cross-Contamination Due to Food Handling Practices: A Mini-Review.

Celiac disease (CD) is an autoimmune disease triggered by the ingestion of gluten in genetically predisposed individuals, affecting 1.4% of the world population. CD induces an inflammatory reaction that compromises small intestine villi, leading to nutrient malabsorption, and gastro and extraintestinal manifestations. Although other treatment approaches are being studied, adherence to a gluten-free diet (GFD) is the only effective intervention to date. Despite this, about 50% of patients experience persistent inflammation, often associated with unintentional gluten ingestion through contaminated food. There are regulations for labeling gluten-free foods which specify a limit of 20 mg/kg (20 ppm). The risks of gluten cross-contamination above that level are present throughout the whole food production chain, emphasizing the need for caution. This review explores studies that tested different procedures regarding the shared production of gluten-containing and gluten-free food, including the use of shared equipment and utensils. A literature review covering PubMed, Scielo, Web of Science, VHL and Scopus identified five relevant studies. The results indicate that shared environments and equipment may not significantly increase gluten cross-contamination if appropriate protocols are followed. Simultaneous cooking of gluten-containing and gluten-free pizzas in shared ovens has demonstrated a low risk of contamination. In general, shared kitchen utensils and equipment (spoon, ladle, colander, knife, fryer, toaster) in controlled experiments did not lead to significant contamination of samples. On the other hand, cooking gluten-free and gluten-containing pasta in shared water resulted in gluten levels above the established limit of 20 ppm. However, rinsing the pasta under running water for a few seconds was enough to reduce the gluten content of the samples to less than 20 ppm.

Gastrointestinal Acute Radiation Syndrome: Mechanisms, Models, Markers, and Medical Countermeasures.

There have been a number of reported human exposures to high dose radiation, resulting from accidents at nuclear power plants (e.g., Chernobyl), atomic bombings (Hiroshima and Nagasaki), and mishaps in industrial and medical settings. If absorbed radiation doses are high enough, evolution of acute radiation syndromes (ARS) will likely impact both the bone marrow as well as the gastrointestinal (GI) tract. Damage incurred in the latter can lead to nutrient malabsorption, dehydration, electrolyte imbalance, altered microbiome and metabolites, and impaired barrier function, which can lead to septicemia and death. To prepare for a medical response should such an incident arise, the National Institute of Allergy and Infectious Diseases (NIAID) funds basic and translational research to address radiation-induced GI-ARS, which remains a critical and prioritized unmet need. Areas of interest include identification of targets for damage and mitigation, animal model development, and testing of medical countermeasures (MCMs) to address GI complications resulting from radiation exposure. To appropriately model expected human responses, it is helpful to study analogous disease states in the clinic that resemble GI-ARS, to inform on best practices for diagnosis and treatment, and translate them back to inform nonclinical drug efficacy models. For these reasons, the NIAID partnered with two other U.S. government agencies (the Biomedical Advanced Research and Development Authority, and the Food and Drug Administration), to explore models, biomarkers, and diagnostics to improve understanding of the complexities of GI-ARS and investigate promising treatment approaches. A two-day workshop was convened in August 2022 that comprised presentations from academia, industry, healthcare, and government, and highlighted talks from 26 subject matter experts across five scientific sessions. This report provides an overview of information that was presented during the conference, and important discussions surrounding a broad range of topics that are critical for the research, development, licensure, and use of MCMs for GI-ARS.

Influence of Bariatric Surgery on Gut Microbiota Composition and Its Implication on Brain and Peripheral Targets.

Obesity remains a significant global health challenge, with bariatric surgery remaining as one of the most effective treatments for severe obesity and its related comorbidities. This review highlights the multifaceted impact of bariatric surgery beyond mere physical restriction or nutrient malabsorption, underscoring the importance of the gut microbiome and neurohormonal signals in mediating the profound effects on weight loss and behavior modification. The various bariatric surgery procedures, such as Roux-en-Y gastric bypass (RYGB) and sleeve gastrectomy (SG), act through distinct mechanisms to alter the gut microbiome, subsequently impacting metabolic health, energy balance, and food reward behaviors. Emerging evidence has shown that bariatric surgery induces profound changes in the composition of the gut microbiome, notably altering the Firmicutes/Bacteroidetes ratio and enhancing populations of beneficial bacteria such as Akkermansia. These microbiota shifts have far-reaching effects beyond gut health, influencing dopamine-mediated reward pathways in the brain and modulating the secretion and action of key gut hormones including ghrelin, leptin, GLP-1, PYY, and CCK. The resultant changes in dopamine signaling and hormone levels contribute to reduced hedonic eating, enhanced satiety, and improved metabolic outcomes. Further, post-bariatric surgical effects on satiation targets are in part mediated by metabolic byproducts of gut microbiota like short-chain fatty acids (SCFAs) and bile acids, which play a pivotal role in modulating metabolism and energy expenditure and reducing obesity-associated inflammation, as well as influencing food reward pathways, potentially contributing to the regulation of body weight and reduction in hedonic eating behaviors. Overall, a better understanding of these mechanisms opens the door to developing non-surgical interventions that replicate the beneficial effects of bariatric surgery on the gut microbiome, dopamine signaling, and gut hormone regulation, offering new avenues for obesity treatment.

Erythrocyte and iron profiles in soil-transmitted helminth-infected children in a rural area in Banten, Indonesia

BACKGROUND Soil-transmitted helminth (STH) infection, frequently caused by Ascaris lumbricoides, Trichuris trichiura, and hookworms (Ancylostoma duodenale and Necator americanus), often gives rise to malabsorption of nutrients that form hemoglobin (Hb) thereby causing anemia. This study aimed to know the difference in erythrocyte profile in children with and without STH infections. METHODS This cross-sectional study involved 205 children from two Panimbang Jaya elementary schools in Pandeglang, Banten, Indonesia. Blood and stool samples were collected from a previous study conducted from November 2021 to May 2022. Erythrocyte parameters were Hb concentration, erythrocyte count, mean corpuscular volume (MCV), mean corpuscular Hb (MCH), and red cell distribution width (RDW). The iron profile included serum iron, total iron-biding capacity (TIBC), and ferritin. Worm infestation was detected by direct stool microscopical examination. Statistical analysis was performed using SPSS software version 20. RESULTS The prevalence of STH infection in Pandeglang was 44.4%, primarily characterized by mild intensity STH infection (79%). The identified STH species were A. lumbricoides, T. trichiura, and combination of both. The median differences between erythrocyte count, MCV, and MCH, and the mean differences of TIBC and serum iron were not statistically significant (p = 0.388, 0.098, and 0.057, and p = 0.304 and 0.455). However, children with STH infection had lower Hb (12.57 versus 12.95 g/dl) and ferritin (19.60 versus 30.57 µg/dl) levels but higher RDW (13.20 versus 13.10%). CONCLUSIONS A high prevalence of STH infection was identified among schoolchildren, but their erythrocyte profiles were similar regardless of STH infection status.

Cystic fibrosis and fat malabsorption: Pathophysiology of the cystic fibrosis gastrointestinal tract and the impact of highly effective CFTR modulator therapy.

Cystic fibrosis (CF) is a progressive, genetic, multi-organ disease affecting the respiratory, digestive, endocrine, and reproductive systems. CF can affect any aspect of the gastrointestinal (GI) tract, including the esophagus, stomach, small intestine, colon, pancreas, liver, and gall bladder. GI pathophysiology associated with CF results from CF membrane conductance regulator (CFTR) dysfunction. The majority of people with CF (pwCF) experience exocrine pancreatic insufficiency resulting in malabsorption of nutrients and malnutrition. Additionally, other factors can cause or worsen fat malabsorption, including the potential for short gut syndrome with a history of meconium ileus, hepatobiliary diseases, and disrupted intraluminal factors, such as inadequate bile salts, abnormal pH, intestinal microbiome changes, and small intestinal bacterial overgrowth. Signs and symptoms associated with fat malabsorption, such as abdominal pain, bloating, malodorous flatus, gastroesophageal reflux, nausea, anorexia, steatorrhea, constipation, and distal intestinal obstruction syndrome, are seen in pwCF despite the use of pancreatic enzyme replacement therapy. Given the association of poor nutrition status with lung function decline and increased mortality, aggressive nutrition support is essential in CF care to optimize growth in children and to achieve and maintain a healthy body mass index in adults. The introduction of highly effective CFTR modulator therapy and other advances in CF care have profoundly changed the course of CF management. However, GI symptoms in some pwCF may persist. The use of current knowledge of the pathophysiology of the CF GI tract as well as appropriate, individualized management of GI symptoms continue to be integral components of care for pwCF.