{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,2,27]],"date-time":"2026-02-27T05:10:29Z","timestamp":1772169029486,"version":"3.50.1"},"reference-count":23,"publisher":"F1000 Research Ltd","license":[{"start":{"date-parts":[[2018,8,2]],"date-time":"2018-08-02T00:00:00Z","timestamp":1533168000000},"content-version":"tdm","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/501100000265","name":"Medical Research Council","doi-asserted-by":"publisher","id":[{"id":"10.13039\/501100000265","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100004440","name":"Wellcome Trust","doi-asserted-by":"publisher","award":["203077"],"award-info":[{"award-number":["203077"]}],"id":[{"id":"10.13039\/100004440","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["wellcomeopenresearch.org"],"crossmark-restriction":false},"short-container-title":["Wellcome Open Res"],"abstract":"\n Background:<\/ns3:bold>\n Changes in intestinal mucosal integrity and gut microbial balance occur in severe acute malnutrition (SAM), resulting in treatment failure and adverse clinical outcomes (gram-negative sepsis, diarrhoea and high case-fatality). Transient lactose intolerance, due to loss of intestinal brush border lactase, also complicates SAM, thus milk based feeds may not be optimal for nutritional rehabilitation. Since the gut epithelial barrier can be supported by short chain fatty acids, derived from microbiota fermentation by particular fermentable carbohydrates, we postulated that an energy-dense nutritional feed comprising of legume-based fermentable carbohydrates, incorporated with lactose-free versions of standard World Health Organization (WHO) F75\/F100 nutritional feeds will enhance epithelial barrier function in malnourished children, reduce and promote resolution of diarrhoea and improve overall outcome.\n <\/ns3:p>\n \n Methods:<\/ns3:bold>\n We will investigate in an open-label trial in 160 Ugandan children with SAM, defined by mid-upper arm circumference <11.5cm and\/or presence of kwashiorkor. Children will be randomised to a lactose-free, chickpea-enriched feed containing 2 kcal\/ml, provided in quantities to match usual energy provision (experimental) or WHO standard treatment F75 (0.75 kcal\/ml) and F100 (1 kcal\/ml) feeds on a 1:1 basis, conducted at Mbale Regional Referral Hospital nutritional rehabilitation unit. The primary outcomes are change in MUAC at day 90 and survival to day 90. Secondary outcomes include: i) moderate to good weight gain (>5 g\/kg\/day), ii)\n de novo<\/ns3:italic>\n development of diarrhoea (>3 loose stools\/day), iii) time to diarrhoea resolution (if >3 loose stools\/day), and iv) time to oedema resolution (if kwashiorkor) and change in intestinal biomarkers (faecal calprotectin).\n <\/ns3:p>\n \n Discussion:<\/ns3:bold>\n We hypothesize that, if introduced early in the management of malnutrition, such lactose-free, fermentable carbohydrate-based feeds, could safely and cheaply improve global outcome by reducing lactose intolerance-related diarrhoea, improving mucosal integrity and enhancing immunity, and limiting the risk of systemic infection and associated broad-spectrum antibiotic resistance.\n <\/ns3:p>\n \n Registration:<\/ns3:bold>\n ISRCTN 10309022<\/ns3:ext-link>\n .\n <\/ns3:p>","DOI":"10.12688\/wellcomeopenres.14706.1","type":"journal-article","created":{"date-parts":[[2018,8,2]],"date-time":"2018-08-02T12:00:19Z","timestamp":1533211219000},"page":"95","update-policy":"https:\/\/doi.org\/10.12688\/wellcomeopenres.crossmark-policy","source":"Crossref","is-referenced-by-count":8,"title":["Modifying Intestinal Integrity and MicroBiome in Severe Malnutrition with Legume-Based Feeds (MIMBLE 2.0): protocol for a phase II refined feed and intervention trial"],"prefix":"10.12688","volume":"3","author":[{"ORCID":"https:\/\/orcid.org\/0000-0001-7943-0502","authenticated-orcid":false,"given":"Kevin","family":"Walsh","sequence":"first","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Nuala","family":"Calder","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-5757-609X","authenticated-orcid":false,"given":"Peter","family":"Olupot-Olupot","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Tonny","family":"Ssenyondo","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"William","family":"Okiror","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Charles 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status","group":{"name":"current-referee-status","label":"Current Referee Status"}},{"value":"10.21956\/wellcomeopenres.16015.r33640, Thomas Preston, Scottish Universities Environmental Research Centre, East Kilbride, UK, 31 Aug 2018, version 1, indexed","URL":"https:\/\/wellcomeopenresearch.org\/articles\/3-95\/v1#referee-response-33640","order":0,"name":"referee-response-33640","label":"Referee Report","group":{"name":"article-reports","label":"Article Reports"}},{"value":"10.21956\/wellcomeopenres.16015.r33704, Paluku Bahwere, Valid International, Oxford, UK, 24 Sep 2018, version 1, indexed","URL":"https:\/\/wellcomeopenresearch.org\/articles\/3-95\/v1#referee-response-33704","order":1,"name":"referee-response-33704","label":"Referee Report","group":{"name":"article-reports","label":"Article Reports"}},{"value":"This study is funded by the MRC Confidence in Concept 2017 Scheme which is also supported by GCRF funding, and led by the Wellcome Trust Centre for Global Health Research (grant number 203077) in conjunction with the Institute for Global Health Innovation, at Imperial College London. The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript.","order":2,"name":"grant-information","label":"Grant Information"},{"value":"This is an open access article distributed under the terms of the Creative Commons Attribution Licence, which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.","order":0,"name":"copyright-info","label":"Copyright"}]}}