Association of faecal pH with childhood stunting: Results from a cross-sectional study

Md Shabab Hossain, Subhasish Das, Md Amran Gazi, Md Ashraful Alam, Nur Muhammad Shahedul Haque, Mustafa Mahfuz, Tahmeed Ahmed, Chris J Damman, Md Shabab Hossain, Subhasish Das, Md Amran Gazi, Md Ashraful Alam, Nur Muhammad Shahedul Haque, Mustafa Mahfuz, Tahmeed Ahmed, Chris J Damman

Abstract

Background: Gut microbiota plays an important role in the growth of children. The gut of children with optimum growth is enriched in certain species, especially Bifidobacteria and Clostridia. Bifidobacteria and commensal Clostridia both contribute to formation of acidic stool, and an elevated faecal pH indicates reduction of these species in the gut. The purpose of the study was to investigate the association of faecal pH with childhood stunting.

Methods: In this cross-sectional study, 100 children with length-for-age Z score (LAZ) <-1 aged between 12 and 18 months were enrolled from the ongoing Bangladesh Environmental Enteric Dysfunction study conducted in Dhaka, Bangladesh. LAZ was measured by anthropometry and data on factors affecting linear growth were recorded. Faecal pH measurement was done using pH metre on freshly collected non-diarrhoeal faecal samples following standard procedure. Multiple quantile regression was done to quantify the relation between faecal pH and LAZ scores.

Results: The mean LAZ and faecal pH of the children were -2.12±0.80 and 5.84±1.11, respectively. Pearson correlation analysis showed a statistically significant negative correlation between stool pH and the LAZ scores (p<0.01). After inclusion of other factors affecting linear growth into the regression model, a statistically significant inverse association was observed between faecal pH and LAZ score (p<0.01).

Conclusion: Elevated faecal pH was found to have a significant association with stunted growth. As an indicator of gut microbiota status, faecal pH might have emerged as a possible indirect determinant of childhood stunting.

Trial registration number: NCT02812615.

Keywords: Bangladesh; Faecal pH; children; growth.

Conflict of interest statement

Competing interests: None declared.

© Author(s) (or their employer(s)) 2019. Re-use permitted under CC BY. Published by BMJ.

Figures

Figure 1
Figure 1
Scatter diagram showing negative correlation between faecal pH and LAZ scores. LAZ, length-for-age Z score.

References

    1. Black RE, Victora CG, Walker SP, et al. . Maternal and child undernutrition and overweight in low-income and middle-income countries. The Lancet 2013;382:427–51. 10.1016/S0140-6736(13)60937-X
    1. Farràs M, Chandwe K, Mayneris-Perxachs J, et al. . Characterizing the metabolic phenotype of intestinal villus blunting in Zambian children with severe acute malnutrition and persistent diarrhea. PLoS One 2018;13:e0192092 10.1371/journal.pone.0192092
    1. Amadi B, Besa E, Zyambo K, et al. . Impaired barrier function and autoantibody generation in malnutrition enteropathy in Zambia. EBioMedicine 2017;22:191–9. 10.1016/j.ebiom.2017.07.017
    1. Dinh DM, Ramadass B, Kattula D, et al. . Longitudinal analysis of the intestinal microbiota in persistently stunted young children in South India. PLoS One 2016;11:e0155405 10.1371/journal.pone.0155405
    1. Grantham-McGregor S, Cheung YB, Cueto S, et al. . Developmental potential in the first 5 years for children in developing countries. The Lancet 2007;369:60–70. 10.1016/S0140-6736(07)60032-4
    1. Harper KM, Mutasa M, Prendergast AJ, et al. . Environmental enteric dysfunction pathways and child stunting: a systematic review. PLoS Negl Trop Dis 2018;12:e0006205 10.1371/journal.pntd.0006205
    1. Kane AV, Dinh DM, Ward HD. Childhood malnutrition and the intestinal microbiome. Pediatr Res 2015;77:256–62. 10.1038/pr.2014.179
    1. Kau AL, Ahern PP, Griffin NW, et al. . Human nutrition, the gut microbiome and the immune system. Nature 2011;474:327–36. 10.1038/nature10213
    1. Gordon JI, Dewey KG, Mills DA, et al. . The human gut microbiota and undernutrition. Sci Transl Med 2012;4:137ps12 10.1126/scitranslmed.3004347
    1. Dewey KG, Begum K. Long-Term consequences of stunting in early life. Matern Child Nutr 2011;7:5–18. 10.1111/j.1740-8709.2011.00349.x
    1. Keusch GT, Rosenberg IH, Denno DM, et al. . Implications of acquired environmental enteric dysfunction for growth and stunting in infants and children living in low- and middle-income countries. Food Nutr Bull 2013;34:357–64. 10.1177/156482651303400308
    1. Keusch GT, Denno DM, Black RE, et al. . Environmental enteric dysfunction: pathogenesis, diagnosis, and clinical consequences. Clin Infect Dis 2014;59(suppl_4):S207–12. 10.1093/cid/ciu485
    1. Investigators M-EN. Childhood stunting in relation to the pre-and postnatal environment during the first 2 years of life: the MAL-ED longitudinal birth cohort study. PLoS medicine 2017;14:e1002408.
    1. Donowitz JR, Haque R, Kirkpatrick BD, et al. . Small intestine bacterial overgrowth and environmental enteropathy in Bangladeshi children. MBio 2016;7:e02102–15. 10.1128/mBio.02102-15
    1. Gough EK, Stephens DA, Moodie EEM, et al. . Linear growth faltering in infants is associated with Acidaminococcus sp. and community-level changes in the gut microbiota. Microbiome 2015;3 10.1186/s40168-015-0089-2
    1. Bäckhed F, Ley RE, Sonnenburg JL. Host-Bacterial mutualism in the human intestine. Science 2005;307:1915–20. 10.1126/science.1104816
    1. O'Hara AM, Shanahan F. The gut flora as a forgotten organ. EMBO Rep 2006;7:688–93. 10.1038/sj.embor.7400731
    1. Evans JM, Morris LS, Marchesi JR. The gut microbiome: the role of a virtual organ in the endocrinology of the host. J Endocrinol 2013;218:R37–47. 10.1530/JOE-13-0131
    1. Henrick BM, Hutton AA, Palumbo MC, et al. . Elevated Fecal pH Indicates a Profound Change in the Breastfed Infant Gut Microbiome Due to Reduction of Bifidobacterium over the Past Century. mSphere 2018;3:e00041–18. 10.1128/mSphere.00041-18
    1. Vonaesch P, Morien E, Andrianonimiadana L, et al. . Stunted childhood growth is associated with decompartmentalization of the gastrointestinal tract and overgrowth of oropharyngeal taxa. Proc Natl Acad Sci U S A 2018;115:E8489–98. 10.1073/pnas.1806573115
    1. Lopetuso LR, Scaldaferri F, Petito V, et al. . Commensal clostridia: leading players in the maintenance of gut homeostasis. Gut Pathog 2013;5:23 10.1186/1757-4749-5-23
    1. Mahfuz M, Das S, Mazumder RN, et al. . Bangladesh environmental enteric dysfunction (BEED) study: protocol for a community-based intervention study to validate non-invasive biomarkers of environmental enteric dysfunction. BMJ Open 2017;7:e017768 10.1136/bmjopen-2017-017768
    1. de Onis M, Group WMGRS . Reliability of anthropometric measurements in the who multicentre growth reference study. Acta Paediatrica 2006;95:38–46.
    1. Kosek M, Guerrant RL, Kang G, et al. . Assessment of environmental enteropathy in the MAL-ED cohort study: theoretical and analytic framework. Clin Infect Dis 2014;59(Suppl 4):S239–47. 10.1093/cid/ciu457
    1. Acosta AM, Chavez CB, Flores JT, et al. . The MAL-ED study: a multinational and multidisciplinary approach to understand the relationship between enteric pathogens, malnutrition, gut physiology, physical growth, cognitive development, and immune responses in infants and children up to 2 years of age in resource-poor environments. Clin Infect Dis 2014;59(Suppl 4):S193–206. 10.1093/cid/ciu653
    1. Osuka A, Shimizu K, Ogura H, et al. . Prognostic impact of fecal pH in critically ill patients. Critical Care 2012;16 10.1186/cc11413
    1. Gasbarrini A, Corazza GR, Gasbarrini G, et al. . Methodology and indications of H2-breath testing in gastrointestinal diseases: the Rome consensus conference. Aliment Pharmacol Ther 2009;29(Suppl 1):1–49. 10.1111/j.1365-2036.2009.03951.x
    1. Stein AD, Wang M, Martorell R, et al. . Growth patterns in early childhood and final attained stature: data from five birth cohorts from low- and middle-income countries. Am J Hum Biol 2010;22:353–9. 10.1002/ajhb.20998
    1. Psaki SR, Seidman JC, Miller M, et al. . Measuring socioeconomic status in multicountry studies: results from the eight-country MAL-ED study. Popul Health Metr 2014;12:8 10.1186/1478-7954-12-8
    1. Kvissberg MA, Dalvi PS, Kerac M, et al. . Carbohydrate malabsorption in acutely malnourished children and infants: a systematic review. Nutr Rev 2016;74:48–58. 10.1093/nutrit/nuv058
    1. Betrán AP, Ye J, Moller A-B, et al. . The increasing trend in caesarean section rates: global, regional and national estimates: 1990-2014. PLoS One 2016;11:e0148343 10.1371/journal.pone.0148343
    1. Duranti S, Lugli GA, Mancabelli L, et al. . Prevalence of antibiotic resistance genes among human gut-derived bifidobacteria. Appl Environ Microbiol 2017;83:e02894–16. 10.1128/AEM.02894-16
    1. Rivera-Chávez F, Zhang LF, Faber F, et al. . Depletion of butyrate-producing clostridia from the gut microbiota drives an aerobic luminal expansion of Salmonella. Cell Host Microbe 2016;19:443–54. 10.1016/j.chom.2016.03.004
    1. Logan WR. The intestinal flora of infants and young children. J Pathol Bacteriol 1913;18:527–51. 10.1002/path.1700180154
    1. Akter S, Rahman MM. Duration of breastfeeding and its correlates in Bangladesh. J Health Popul Nutr 2010;28:595 10.3329/jhpn.v28i6.6608
    1. Voth-Gaeddert LE, Torres O, Maldonado J, et al. . Aflatoxin exposure, child stunting, and dysbiosis in the intestinal microbiome among children in Guatemala. Environ Eng Sci 2019;36:958–68. 10.1089/ees.2019.0104
    1. Dukowicz AC, Lacy BE, Levine GM. Small intestinal bacterial overgrowth: a comprehensive review. Gastroenterol Hepatol 2007;3.
    1. Gasbarrini A, Lauritano EC, Gabrielli M, et al. . Small intestinal bacterial overgrowth: diagnosis and treatment. Dig Dis 2007;25:237–40. 10.1159/000103892
    1. Vonaesch P, Anderson M, Sansonetti PJ. Pathogens, microbiome and the host: emergence of the ecological Koch's postulates. FEMS Microbiol Rev 2018;42:273–92. 10.1093/femsre/fuy003
    1. Atarashi K, Tanoue T, Shima T, et al. . Induction of colonic regulatory T cells by Indigenous Clostridium species. Science 2011;331:337–41. 10.1126/science.1198469
    1. Underwood MA, German JB, Lebrilla CB, et al. . Bifidobacterium longum subspecies infantis: champion colonizer of the infant gut. Pediatr Res 2015;77:229–35. 10.1038/pr.2014.156
    1. Bode L. Recent advances on structure, metabolism, and function of human milk oligosaccharides. J Nutr 2006;136:2127–30. 10.1093/jn/136.8.2127

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