{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,5,14]],"date-time":"2026-05-14T20:28:07Z","timestamp":1778790487793,"version":"3.51.4"},"reference-count":33,"publisher":"American Society of Tropical Medicine and Hygiene","issue":"4","license":[{"start":{"date-parts":[[2025,4,2]],"date-time":"2025-04-02T00:00:00Z","timestamp":1743552000000},"content-version":"unspecified","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":[],"published-print":{"date-parts":[[2025,4,2]]},"abstract":"<jats:title>ABSTRACT.<\/jats:title>\n<jats:p>Environmental enteric dysfunction (EED) is a subacute syndrome characterized by increased intestinal inflammation and permeability that affects children in low-income countries. It is associated with growth and neurodevelopmental deficits, and there is currently no known treatment for EED. VS001 (AmiLyfe Bioscience, LLC, Norwood, MA) is a medical food (beverage) containing free amino acids that has been shown to decrease enteric inflammation and improve gut permeability in murine models. We conducted a double-blind, placebo-controlled pilot study to assess the acceptability and tolerability of VS001 in Bangladeshi children aged 1\u20132 years (<jats:italic>n<\/jats:italic> = 10 per arm). We also examined the effects on EED biomarkers (lactulose\u2013mannitol (LM) ratio, fecal lactoferrin, alpha-antitrypsin, myeloperoxidase, and neopterin). Participants received 8 oz. of VS001 or an identical vehicle without amino acids daily for 14 days. Tolerability and acceptability were measured using parental surveys and daily in-home adverse event monitoring. Subjects took an average of 118 minutes to complete the dose each day. Caregivers found the product convenient and easy to administer and either agreed or strongly agreed that they would give this product to their child again. None reported that the intervention negatively affected their child\u2019s appetite. There were three mild adverse events deemed possibly related to the intervention, with two occurring in the active arm and one in the control arm. Children in the active arm exhibited a nonsignificant decrease in LM ratios (a marker of intestinal permeability) after treatment compared with the control arm (0.19\u20130.08 versus 0.19\u20130.17; <jats:italic>P<\/jats:italic> = 0.16). VS001 was acceptable to parents and reasonably well tolerated. Given the decrease in permeability observed in the active arm, a larger trial is warranted.<\/jats:p>","DOI":"10.4269\/ajtmh.24-0402","type":"journal-article","created":{"date-parts":[[2025,2,7]],"date-time":"2025-02-07T18:24:05Z","timestamp":1738952645000},"page":"859-864","source":"Crossref","is-referenced-by-count":3,"title":["A Pilot Study of Enterade (VS001), an Oral Amino Acid Formulation, in Malnourished Bangladeshi Children with Environmental Enteric Dysfunction"],"prefix":"10.4269","volume":"112","author":[{"given":"Masud","family":"Alam","sequence":"first","affiliation":[{"name":"Infectious Diseases Division, International Centre for Diarrhoeal Disease Research, Bangladesh, Dhaka, Bangladesh;"},{"name":"Vaccine Testing Center, University of Vermont, Burlington, Vermont;"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Tahsin","family":"Ferdous","sequence":"additional","affiliation":[{"name":"Infectious Diseases Division, International Centre for Diarrhoeal Disease Research, Bangladesh, Dhaka, Bangladesh;"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Rifat","family":"Ara","sequence":"additional","affiliation":[{"name":"Infectious Diseases Division, International Centre for Diarrhoeal Disease Research, Bangladesh, Dhaka, Bangladesh;"},{"name":"University College London, London, United Kingdom;"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Abdulla","family":"Siddique","sequence":"additional","affiliation":[{"name":"Infectious Diseases Division, International Centre for Diarrhoeal Disease Research, Bangladesh, Dhaka, Bangladesh;"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Mamun","family":"Kabir","sequence":"additional","affiliation":[{"name":"Infectious Diseases Division, International Centre for Diarrhoeal Disease Research, Bangladesh, Dhaka, Bangladesh;"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Rashidul","family":"Haque","sequence":"additional","affiliation":[{"name":"Infectious Diseases Division, International Centre for Diarrhoeal Disease Research, Bangladesh, Dhaka, Bangladesh;"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Jeffrey R.","family":"Donowitz","sequence":"additional","affiliation":[{"name":"Division of Pediatric Infectious Diseases, Children\u2019s Hospital of Richmond at Virginia Commonwealth University, Richmond, Virginia;"},{"name":"Division of Pediatric Infectious Diseases, University of Virginia, Charlottesville, Virginia"}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"2795","reference":[{"key":"b1","series-title":"Nat Rev Gastroenterol Hepatol","first-page":"220","article-title":"The impoverished gut\u2014A triple burden of diarrhoea, stunting and chronic disease","volume":"10","author":"Guerrant","year":"2013"},{"key":"b2","series-title":"EBioMedicine","first-page":"1759","article-title":"Environmental enteropathy, oral vaccine failure and growth faltering in infants in Bangladesh","volume":"2","author":"Naylor","year":"2015"},{"key":"b3","series-title":"Am J Clin Nutr","first-page":"1129","article-title":"REG1B as a predictor of childhood stunting in Bangladesh and Peru","volume":"97","author":"Peterson","year":"2013"},{"key":"b4","series-title":"Lancet","first-page":"519","article-title":"Intestinal biopsy in Kwashiorkor","volume":"2","author":"Stanfield","year":"1965"},{"key":"b5","series-title":"Clin Infect Dis","first-page":"S239","article-title":"Assessment of environmental enteropathy in the MAL-ED cohort study: Theoretical and analytic framework","volume":"59 (Suppl 4)","author":"Kosek","year":"2014"},{"key":"b6","series-title":"Am J Trop Med Hyg","first-page":"390","article-title":"Fecal markers of intestinal inflammation and permeability associated with the subsequent acquisition of linear growth deficits in infants","volume":"88","author":"Kosek","year":"2013"},{"key":"b7","series-title":"Trends Mol Med","first-page":"328","article-title":"Environmental enteropathy: Critical implications of a poorly understood condition","volume":"18","author":"Korpe","year":"2012"},{"key":"b8","series-title":"PLOS Negl Trop Dis","first-page":"e0006363","article-title":"Role of maternal health and inflammation in infancy in nutritional and neurodevelopmental outcomes of two-year-old Bangladeshi children","volume":"12","author":"Donowitz","year":"2018"},{"key":"b9","series-title":"J Infect Dis","first-page":"1794","article-title":"Etiology of diarrhea in Bangladeshi infants in the first year of life analyzed using molecular methods","volume":"208","author":"Taniuchi","year":"2013"},{"key":"b10","series-title":"Lancet","first-page":"907","article-title":"Intestinal permeability, mucosal injury, and growth faltering in Gambian infants","volume":"338","author":"Lunn","year":"1991"},{"key":"b11","series-title":"Lancet Glob Health","first-page":"e564","article-title":"Pathogen-specific burdens of community diarrhoea in developing countries: A multisite birth cohort study (MAL-ED)","volume":"3","author":"Platts-Mills","year":"2015"},{"key":"b12","series-title":"Clin Infect Dis","first-page":"S213","article-title":"Use of the lactulose to mannitol ratio to evaluate childhood environmental enteric dysfunction: A systematic review","volume":"59 (Suppl 4)","author":"Denno","year":"2014"},{"key":"b13","series-title":"BMC Med","first-page":"181","article-title":"Environmental enteric dysfunction: A review of potential mechanisms, consequences and management strategies","volume":"17","author":"Tickell","year":"2019"},{"key":"b14","series-title":"J Pediatr Gastroenterol Nutr","first-page":"6","article-title":"Environmental enteric dysfunction in children","volume":"63","author":"Syed","year":"2016"},{"key":"b15","series-title":"Adv Cancer Res","doi-asserted-by":"crossref","first-page":"131","DOI":"10.1016\/bs.acr.2022.02.007","article-title":"Chemotherapy induced gastrointestinal toxicities","volume":"155","author":"Akbarali","year":"2022"},{"key":"b16","series-title":"Health Phys","first-page":"734","article-title":"An amino acid mixture mitigates radiation-induced gastrointestinal toxicity","volume":"106","author":"Yin","year":"2014"},{"key":"b17","series-title":"Sci Rep","first-page":"37220","article-title":"An amino acid-based oral rehydration solution (AA-ORS) enhanced intestinal epithelial proliferation in mice exposed to radiation","volume":"6","author":"Yin","year":"2016"},{"key":"b18","series-title":"J Nutr","first-page":"1100","article-title":"An amino acid-based oral rehydration solution regulates radiation-induced intestinal barrier disruption in mice","volume":"150","author":"Gupta","year":"2020"},{"key":"b19","series-title":"BMC Cancer","first-page":"580","article-title":"Can an amino acid mixture alleviate gastrointestinal symptoms in neuroendocrine tumor patients?","volume":"21","author":"Chauhan","year":"2021"},{"key":"b20","series-title":"Asian Pac J Cancer Prev","first-page":"301","article-title":"Randomized study of Enterade\u00ae to reduce diarrhea in patients receiving high-dose chemotherapy and autologous hematopoietic stem cell transplantation","volume":"22","author":"De Filipp","year":"2021"},{"key":"b21","series-title":"PLoS One","first-page":"e0220397","article-title":"Measurement of intestinal permeability using lactulose and mannitol with conventional five hours and shortened two hours urine collection by two different methods: HPAE-PAD and LC-MSMS","volume":"14","author":"Musa","year":"2019"},{"key":"b22","series-title":"Clin Infect Dis","first-page":"738","article-title":"Effects of water, sanitation, handwashing, and nutritional interventions on environmental enteric dysfunction in young children: A cluster-randomized, controlled trial in rural Bangladesh","volume":"70","author":"Lin","year":"2020"},{"key":"b23","series-title":"Lancet Glob Health","first-page":"e1139","article-title":"The WASH Benefits and SHINE trials: Interpretation of WASH intervention effects on linear growth and diarrhoea","volume":"7","author":"Pickering","year":"2019"},{"key":"b24","series-title":"Lancet Child Adolesc Health","first-page":"255","article-title":"Effect of water quality, sanitation, hand washing, and nutritional interventions on child development in rural Bangladesh (WASH Benefits Bangladesh): A cluster-randomised controlled trial","volume":"2","author":"Tofail","year":"2018"},{"key":"b25","series-title":"BMC Med","first-page":"133","article-title":"Mesalazine in the initial management of severely acutely malnourished children with environmental enteric dysfunction: A pilot randomized controlled trial","volume":"12","author":"Jones","year":"2014"},{"key":"b26","series-title":"Nat Commun","first-page":"2910","article-title":"Malnutrition enteropathy in Zambian and Zimbabwean children with severe acute malnutrition: A multi-arm randomized phase II trial","volume":"15","author":"Chandwe","year":"2024"},{"key":"b27","series-title":"Am J Clin Nutr","first-page":"1040","article-title":"Effect of Lactobacillus GG on intestinal integrity in Malawian children at risk of tropical enteropathy","volume":"82","author":"Galpin","year":"2005"},{"key":"b28","series-title":"N Engl J Med","first-page":"1517","article-title":"A microbiota-directed food intervention for undernourished children","volume":"384","author":"Chen","year":"2021"},{"key":"b29","series-title":"Commun Med (Lond)","first-page":"128","article-title":"Intestinal disturbances associated with mortality of children with complicated severe malnutrition","volume":"3","author":"Wen","year":"2023"},{"key":"b30","series-title":"N Engl J Med","first-page":"425","article-title":"Antibiotics as part of the management of severe acute malnutrition","volume":"368","author":"Trehan","year":"2013"},{"key":"b31","series-title":"Am J Epidemiol","first-page":"2210","article-title":"Identification of etiology-specific diarrhea associated with linear growth faltering in Bangladeshi infants","volume":"187","author":"Schnee","year":"2018"},{"key":"b32","series-title":"Trop Med Int Health","first-page":"1242","article-title":"Association of intestinal pathogens with faecal markers of environmental enteric dysfunction among slum-dwelling children in the first 2 years of life in Bangladesh","volume":"23","author":"Fahim","year":"2018"},{"key":"b33","series-title":"Clin Infect Dis","first-page":"e683","article-title":"Diarrheal pathogens associated with growth and 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