Abstract
Antimicrobial peptides represent an important component of the innate immune defenses of living organisms, including humans. They are broad-spectrum surface-acting agents secreted by the epithelial cells of the body in response to infection. Recently, L-isoleucine and its analogues have been found to induce antimicrobial peptides. The objectives of the study were to examine if addition of L-isoleucine to oral rehydration salts (ORS) solution would reduce stool output and/or duration of acute diarrhoea in children and induce antimicrobial peptides in intestine. This double-blind randomized controlled trial was conducted at the Dhaka Hospital of ICDDR,B. Fifty male children, aged 6-36 months, with acute diarrhoea and some dehydration, attending the hospital, were included in the study. Twenty-five children received L-isoleucine (2 g/L)-added ORS (study), and 25 received ORS without L-isoleucine (control). Stool weight, ORS intake, and duration of diarrhoea were the primary outcomes. There was a trend in reduction in mean +/- standard deviation (SD) daily stool output (g) of children in the L-isoleucine group from day 2 but it was significant on day 3 (388 +/- 261 vs. 653 +/- 446; the difference between mean [95% confidence interval (CI) (-)265 (-509, -20); p = 0.035]. Although the cumulative stool output from day 1 to day 3 reduced by 26% in the isoleucine group, it was not significant. Also, there was a trend in reduction in the mean +/- SD intake of ORS solution (mL) in the L-isoleucine group but it was significant only on day 1 (410 +/- 169 vs. 564 +/- 301), the difference between mean (95% CI) (-)154 (-288, -18); p = 0.04. The duration (hours) of diarrhoea was similar in both the groups. A gradual increase in stool concentrations of beta-defensin 2 and 3 was noted but they were not significantly different between the groups. L-isoleucine-supplemented ORS might be beneficial in reducing stool output and ORS intake in children with acute watery diarrhoea. A further study is warranted to substantiate the therapeutic effect of L-isoleucine.
Highlights
Diarrhoea still accounts for 1.6-2.5 million deaths each year; children in the developing world experience an average of three episodes of diarrhoea each year; and despite the impressive declineL-isoleucine-added ORS in acute diarrhoea and, more importantly, the emergence of resistant pathogens are the major concerns for antimicrobial therapy for diarrhoea as it is for other bacterial infections
We have evaluated orally-administered L-isoleucine in the treatment of acute infectious diarrhoea in infants and young children
Effects of treatment on clinical response. Since this is an exploratory pilot study, we studied 50 patients—25 received L-isoleucine-supplemented ORS (L-isoleucine group), and 25 received ORS without L-isoleucine
Summary
Diarrhoea still accounts for 1.6-2.5 million deaths each year; children in the developing world experience an average of three episodes of diarrhoea each year; and despite the impressive declineL-isoleucine-added ORS in acute diarrhoea and, more importantly, the emergence of resistant pathogens are the major concerns for antimicrobial therapy for diarrhoea as it is for other bacterial infections. Antimicrobial peptides represent an important component of the innate immune defenses of organisms ranging from plants to insects to humans. They are membrane-active agents that kill microbes by various mechanisms [8,9]. Several groups have recently reported the discovery of substances with low molecular weight that induce epithelial antimicrobial peptides in cell-based assays [23,24]. Butyrate has been shown to induce antimicrobial peptides in the colonic epithelial cells and has been shown to exhibit therapeutic benefit in a rabbit model of shigellosis [23]; it cannot be administered orally as such for its foul smell
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