Abstract:
Background: 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.
Methods: 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) de novo 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).
Discussion: 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.
Registration: ISRCTN 10309022.
