Green Banana Reduces Clinical Severity of Childhood Shigellosis: A Double-blind, Randomized, Controlled Clinical Trial

Golam H. Rabbani, MD, PhD, FACG; Shamsir Ahmed, MBBS; Md. Iqbal Hossain, MBBS, PhD; Rafiqul Islam, MBBS, MPH; Farzana Marni, MSc; Mastura Akhtar, MSc; Nashiha Majid, MSc

Disclosures

Pediatr Infect Dis J. 2009;28(5):420-425. 

In This Article

Discussion

This study confirms our earlier observations on the beneficial effects of GB in the management of persistent diarrhea in children[3,4] further showing that GB is also useful in the treatment of invasive dysentery due to Shigella infections. GB added to regular diet produced significant clinical improvement and higher rates of recovery. There was a concurrent stimulation of colonic fatty acid production and a corresponding reduction in fecal myeloperoxidase activity; both supporting the fact that the protective effects of GB are the consequences of colonic fatty acid production and their metabolic actions.

All children in our study in both groups were treated with an effective antibiotic, ciprofloxacin, which is known to modify the clinical and bacteriologic characteristics of shigellosis.[16] Ciprofloxacin given alone for 3 and 5 days produced clinical cure rates of 65% and 69%, respectively, in a comparable groups of Bangladeshi children with shigellosis.[16] By adding GB to ciprofloxacin, we achieved substantially higher cure rates of 85% in similar types of children. Thus, the additional benefits we observed over ciprofloxacin can be attributed to the actions of GB therapy. Because GB given concurrently with ciprofloxacin produces a better effect, it could be a useful therapeutic adjunct in the management of childhood shigellosis. Nevertheless, future studies should explore whether GB alone could be an effective alternative to antibiotics, particularly in treating viral gastroenteritis where antibiotics are not primarily indicated.

Well controlled studies evaluating therapeutic effects of GB in digestive diseases are limited although the role of amylase-resistant starch, the major constituent of GB, has been studied from the metabolic and nutritional point of view.[19,20] Most unripe, green fruits including GB contain resistant starch which escapes digestion in the small bowel and provides fermentable substrates for colonic microflora.[5,6,21,22] GB-resistant starch has poor digestibility in vitro (38%) and in human intestine (32%), and low glycemic index (65%).[20,23] Faisant et al[5,6] reported 84% of raw GB starch is resistant to amylase action in human small intestine and passage through intestine increases its resistance to hydrolysis. Beneficial effects of various types of resistant starch similar to that of GB have been described in patients with colonic diseases including IBD[24,25] and ulcerative colitis[9] and antibacterial effects have been observed against pathogenic bacteria.[24] A maize-based oral rehydration solution and hydrolyzed guar gum (both rich in resistant starch) were found be useful in treating patients with cholera[26] and children with infective diarrhea,[27] respectively. These observations provide supportive evidence for our findings that GB is capable of ameliorating intestinal inflammation and secretion induced by enteric infections.

The mechanisms of GB action have not been well understood. However, it has been observed that administration of resistant starch in human colon leads to increased production of fatty acids, lowered luminal pH, lowered concentrations of ammonia, phenols, and secondary bile acids, and delayed transit time.[28,29] Moreover, bacterial conversion of plant-derived lignans and flavanoids into enteroligans and enterolactones having antioxidative properties[30,31] and inhibitory effects of resistant starch on lactic acid bacteria could be important mechanisms of its cytoprotective effects.[32] Specific interactions of these compounds, alone or in combination with colonic microflora, may lead to mucosal protection against pathogenic bacterial invasion; however, these remain to be elucidated.

Very limited information is available on fatty acid production in children with colonic bacterial infection. Although children up to 2 years are reported to have slower fermentation rates than adults, fecal fatty acid concentrations in our study children are consistent with those reported earlier[33] but were lower at the beginning of GB treatment, increasing afterward by 51% to 157%. This indicates that if colonic microflora is supported with sufficient supply of resistant starch as its metabolic substrate (prebiotic), colonic fermentation in children can be stimulated to produce adequate amounts of fatty acids despite anitibiotic treatment. In our study children, the reason(s) for increased production of fatty acids despite antibacterial effects of ciprofloxacin remain speculative; however, it may be related to complex interrelationship of colonic microflora, dietary substrate (GB), cell metabolism, and products of inflammation. There is paucity of information on the antibacterial effects of ciprofloxacin on colonic microflora, which represents only a fraction of the bacterial population; the diversity of fecal gut flora is considerably higher than anticipated by growing cultivable organisms in vitro.[30] Moreover, starch-based oral solutions have been found to be useful in cholera and noncholera diarrheal patients who also received antibiotics.[26,27]

Reduced fatty acid production in shigellosis may result in loss of mucosal protection and invasion by Shigellae by a variety of mechanisms,[22,24,34] which can be prevented by administration of resistant starch[35] as well as fatty acids.[15] At a molecular level, butyrate increases cellular resistance by decreasing colonic expression of cytokines during shigella infection,[36] inhibits NF-kB,[37,38] induces cyclin-dependent kinase inhibitors,[39,40] and induces the expression of an endogenous antimicrobial peptide (CAP 18), and inhibits expressions of cytokine (γ INF, NF-kB) and heat shock protein 70.[40,41]

We also observed that GB diet significantly reduced fecal MPO activity and numbers of fecal inflammatory cells indicating its anti-inflammatory effects that is associated with concurrent clinical improvement and disappearance of fecal blood and mucus. These observations together with increased fatty acid production provide conclusive evidence that fatty acids are the primary endogenous mediators of GB-induced antiinflammatory effects. Further studies should examine the mechanism of antiinflammatory effects of resistant starch of GB by specifically determining fecal cytokine levels in childhood shigellosis as well as effects of fatty acids on in vitro cell lines.

Regardless of the mechanisms of action, GB has the therapeutic potential to be a useful, safe, and simple antidiarrheal agent that could be incorporated into the standard management of childhood diarrhea using oral rehydration therapy (ORT) and zinc.[42] At present, ORT remains the mainstay of management of diarrhea; nevertheless ORT alone does not reduce stool volume and fecal excretion of blood and mucus, and its utilization rates still remain at below 30% in many developing countries. Where readily available, the addition of GB diet to children over 6 months of age with diarrhea or dysentery holds the potential to be a safe, simple, and affordable adjunct to conventional management that could be easily integrated into primary healthcare programs of many developing countries.

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