Role of Probiotics in Alleviating Diarrheal Diseases in Children

Infectious Diarrhea: Indian scenario

Infectious diarrhea incidence in developing countries is typically six to twelve episodes per child per year, compared to two episodes in the United States. Diarrhea causes over 10% of infant mortality and almost 14% of deaths in children aged 0-4 years in India (1). Bacterial pathogens that have been major culprits include enterotoxigenic E. coli, Shigella, Yersinia, Salmonella, Vibrio cholera, and Campylobacter. In India, antibiotics are prescribed to 75% of pediatric patients for treating diarrhea; however, the fact that viral agents are the most common contributors to pediatric acute diarrhea limits their efficacy, (2) and at the same time increases the burden of antibiotic-associated diarrhea.

Managing Pediatric Diarrheas: Exploring Complementing Treatment Opportunities Beyond ORS & Antibiotics

Despite symptomatic management with oral rehydration solution, continued feeding, oral zinc, and antibiotics for diarrhea of bacterial etiology, there have been no other proven measures for diarrheal illnesses in children (3). Under such situations, pediatric diarrhea continues to be a growing health burden, making it essential to understand better the role of culprit diarrheal pathogens, and changes in gut microbiota composition and explore therapeutic ways to re-establish gut eubiosis. (4)

Over the past 50 years, several studies have focused on effect of probiotics in pediatric gastroenterology due to their ability to modulate the gut microbiome by combating bacterial infections. Known as live microorganisms that, when administered in adequate amounts, confer a health benefit on the host, probiotics help lower the duration and frequency of stools in children and improve the gut’s microbial equilibrium. Probiotics also combat infections on the mucosal surface of the gut. (5) This review aims to unfold the link between pediatric diarrhea and gut microbiome while analyzing the current role of probiotics in managing the same.

Gut microbiota, Diarrhea, and Role of Probiotics: Exploring the link

Gut microbes play an essential part in human health. The resident gut microbiota inhibits pathogen colonization, boosts immune system, generates specific GI hormones and a variety of neuroactive chemicals. Disruptions to a healthy gut microbiota produce gut microbiome imbalance or dysbiosis. (6,7)

Mechanism of action of probiotics in diarrhea;(3)

• Luminal -Many probiotic organisms produce bacteriocins, which inhibit the development or pathogenicity of non-homologous strains. Other probiotic activities, including lactic acid generation, short-chain fatty acid production, and hydrogen peroxide production, reduce intraluminal pH and contribute to a hostile environment for other potentially pathogenic species.
• Mucosal: Certain probiotics can bind directly to invasive species or impede their capacity to interact with or attach to epithelial receptors in other ways. Probiotics, particularly Lactobacillus species, have been demonstrated to increase goblet cell synthesis of mucins and protective ‘trefoil factors’. Trefoil factors are peptides which are widely distributed in the gastrointestinal tract and are known to be involved in the repair of epithelial surfaces.
• Submucosal: The presence of probiotic organisms has also been demonstrated to alter adaptive immune responses, with some able to promote immunoglobulin (especially secretory IgA) synthesis and modulate the formation and activity of regulatory T-lymphocytes. The enteric nervous and endocrine systems are known to be influenced by molecular interactions between host and bacteria.

Understanding Unique Features of Lactobacillus sporogenes in Modulating Gut microbiota:

L. sporogenes has become a focus of research as a spore-forming probiotic bacterium due to its high tolerance to extreme environments (8). L. sporogenes is one of the prominent lactic acid-producing bacteria that share features of both Bacillus and Lactobacillus. (1) L. sporogenes is a facultative anaerobic lactic acid-producing, spore-forming, catalase-positive bacteria. It’s ideal growing temperature is 35-50 °C, and its optimal pH is near 6 for optimal growth. L. sporogenes may break down glucose, sucrose, maltose, and mannitol during growth to create L-lactic acid. (8)

While the clinical applications of probiotics in pediatric gastroenterology range from Acute Infectious Diarrhea (AID), Nosocomial Diarrhea, Antibiotic-Associated Diarrhea (AAD), Traveler’s Diarrhea, Helicobacter pylori Infection, and Infant Colic; research highlights that specific probiotic strains and the patient's age may be the most critical factors determining the antidiarrheal benefits of probiotics. (9)

• Bekkali et al. researched 20 children aged 6 to 16 years who were given probiotics containing Lactobacilli and Bifidobacterium for four weeks. The results of the study revealed that there was a significant decrease in fecal incontinence 4.0 (0.0–35.0) to 0.3 (0.0–7.0) (p = 0.001) and abdominal pain from 45% to 20% (p = 0.006) in four weeks. (10)
• Another study evaluated the efficacy and safety of L. sporogenes in treating acute diarrhea in children between 1 and 12 years of age with AAD and acute infective diarrhea. The results revealed that the probiotic improved recovery and reduced the course of acute infectious diarrhea and AAD in children, with no reported adverse effects. (1)
• In a prospective, double-blind, placebo-controlled study, Chandra et al. investigated the effect of L. sporogenes on the severity of acute rotavirus diarrhea and administered L. sporogenes to infants. Results highlighted a decrease in the episodes of rotavirus diarrhea a (3.4 ± 1.0 vs 8.6 ± 1.7 in the placebo group, p < 0.02) and a reduced duration s (13 ± 3 days vs 35 ± 5 days in the placebo group, p < 0.01) of each episode with a reduction in the number of days of illness/year. (11)

Key Pointers

• Diarrheal diseases significantly cause morbidity and death among children in developing nations.
• The rationale and clinical applicability of probiotics for the prevention and treatment of pediatric diarrhea have been gaining ground rapidly.
• Probiotics in infectious diarrhea work by competing for binding sites and accessible nutrients, producing a range of compounds, and increasing specific and non-specific immune responses.
• L. sporogenes has specific features that make this species stand out among the commonly used probiotics in managing pediatric diarrhea. They include stability in an acidic pH of the stomach and the ability to colonize in an anaerobic GI tract environment. They can form biofilms, which aid in gut colonization, and create different surfactants, which help in gut adherence.

References

1. Dhongade, A. R., Joshi, S. S., Kulkarni, S. V., Jadhav, S. S., Nargundkar, N., Deshmukh, D., & Mehta, A. D. (2022). The Efficacy and Safety of a Bacillus Probiotic Combination for the Treatment of Acute Diarrhea in Children: A Double-blind, Randomized, Placebo-controlled Multicentric Study. Pediatric Infectious Disease, 4(3), 86-91

2. Bari, M. A., & Islam, M. R. (2017). Probiotics: A new horizon for treating childhood diarrhea in Bangladesh. Food and Nutrition Sciences, 8(06), 613.

3. Mandal, A., & Sahi, P. K. (2017). Probiotics for diarrhea in children. Journal of Medical Research and Innovation, 1(2), AV5-AV12.

4. Pop, M., Walker, A. W., Paulson, J., Lindsay, B., Antonio, M., Hossain, M. A., ... & Stine, O. C. (2014). Diarrhea in young children from low-income countries leads to large-scale alterations in intestinal microbiota composition. Genome biology, 15(6), 1-12.

5. Cruchet, S., Furnes, R., Maruy, A., Hebel, E., Palacios, J., Medina, F., ... & Zablah, R. A. (2015). The use of probiotics in pediatric gastroenterology: a review of the literature and recommendations by Latin-American experts. Pediatric Drugs, 17(3), 199-216.

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7. Dudek-Wicher RK, Junka A, Bartoszewicz M. The influence of antibiotics and dietary components on gut microbiota. Prz Gastroenterol 2018;13(2):85–92. 10.5114/pg.2018.76005

8. Cao, J., Yu, Z., Liu, W., Zhao, J., Zhang, H., Zhai, Q., & Chen, W. (2020). Probiotic characteristics of Bacillus coagulans and associated implications for human health and diseases. Journal of Functional Foods, 64, 103643. https://doi.org/10.1016/j.jff.2019.103643

9. Sazawal S, Hiremath G, Dhingra U, et al. Efficacy of probiotics in preventing acute diarrhea: a meta-analysis of masked, randomized, placebo-controlled trials. Lancet Infect Dis 2006;6(6):374–382. DOI: 10.1016/S1473-3099(06)70495-9

10. Bekkali N, Bongers ME, Berg MMVD, et al. The role of a probiotics mixture in treating childhood constipation: a pilot study. Nutr J 2007;6:17. DOI: 10.1186/1475-2891-6-17

11. Chandra RK. Effect of Lactobacillus on the incidence and severity of acute rotavirus diarrhea in infants. A prospective placebo-controlled double-blind study. Nutr Res 2002;22(1–2):65–69. DOI: 10.1016/S0271-5317(01)00367-0