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Other therapies

and other non-pathogenic microbes in the treatment of infectious gastroenteritis. The possible
mechanisms of action include competition with pathogens for binding sites and substrates,
lowering of intestinal luminal pH, production of bacteriocins, promotion of mucin production,
upregulation of genes mediating immunity, and production of trophic short-chain fatty acids
to promote mucosal cell growth and differentiation. The published evidence on the use of
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probiotics in the treatment of children with gastroenteritis was therefore examined.

Evidence overview
Seven studies were identified for inclusion: three systematic reviews 196–198 and four RCTs. 40,199–201

8.5.1 Lactobacillus and saccharomyces yeast probiotics
One systematic review, 196 published in 2003, was conducted to examine the effectiveness of
probiotics compared with control in the treatment of infectious diarrhoea. This well-conducted
systematic review included 23 RCTs published between 1981 and 2002. Fourteen studies were
carried out in developing countries. The included studies enrolled a total of 1917 participants.
Of these, 1449 were children (740 were randomised into the intervention group and 709 into
the control group) and 352 were adults (173 were randomised into the intervention group and
179 into the control group). The participants included were inpatients as well as outpatients.
Although all the studies enrolled participants with acute diarrhoea, definition criteria were
not uniform across the studies. Many studies did not comment on the nutritional status of the
participants but those with underlying severe or chronic illnesses were excluded. Two studies
recruited specifically malnourished children and a further two studies included malnourished
children. The methodology was described in detail and studies were appraised for their quality.
The methodology and design of the trials included in the review were not uniform and only
three studies reported an adequate method of randomisation, allocation concealment, blinding
and loss to follow-up. Different types of probiotic were evaluated and there was a wide range of
treatment regimens. The number of organisms administered, duration of treatment, and timing of
intervention and means of administration varied across all the studies. Data were extracted and
meta-analysis performed for the following outcomes: diarrhoea lasting 3 or more days, diarrhoea
lasting 4 or more days, duration of diarrhoea, and mean stool frequency on day 2 and on day 3.
Other outcomes reported were need for unscheduled IVT and death. [EL = 1++]
The persistence of diarrhoea on day 3 of the intervention was reported in 15 studies (1341
participants). A meta-analysis was performed that showed that those receiving probiotics were
less likely to have diarrhoea lasting 3 or more days (RR 0.66; 95% CI 0.55 to 0.77), but there
was heterogeneity (I² =46.6%) between studies. When data from children were pooled (11 RCTs,
n = 1008), the analysis also showed that statistically significantly more of those receiving placebo
(265/490) had persistence of diarrhoea on day 3 compared with those receiving probiotics
(195/518) (RR 0.68; 95% CI 0.54 to 0.85; I² = 50.2%) (Figure 8.8).

Figure 8.8 Comparison of the effect of probiotics versus placebo on diarrhoea (persistence of diarrhoea on day 3)

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