Differences in immune status and fecal SCFA between Indonesian stunted children and children with normal nutritional status

Ingrid S Surono, Fasli Jalal, Syukrini Bahri, Andreas Romulo, Pratiwi Dyah Kusumo, Erida Manalu, Yusnita, Koen Venema, Ingrid S Surono, Fasli Jalal, Syukrini Bahri, Andreas Romulo, Pratiwi Dyah Kusumo, Erida Manalu, Yusnita, Koen Venema

Abstract

We recently showed that the gut microbiota composition of stunted children was different from that of children with normal nutritional status. Here, we compared immune status and fecal microbial metabolite concentrations between stunted and normal children, and we correlated macronutrient intake (including energy), metabolites and immune status to microbiota composition. The results show that macronutrient intake was lower in stunted children for all components, but after correction for multiple comparison significant only for energy and fat. Only TGF-β was significantly different between stunted children and children of normal nutritional status after correction for multiple comparisons. TNF-alpha, IL-10, lipopolysaccharide binding protein in serum and secretory IgA in feces were not significantly different. Strikingly, all the individual short-chain and branched-chain fatty acids were higher in fecal samples of stunted children (significant for acetate, valerate and total SCFA). These metabolites correlated with a number of different microbial taxa, but due to extensive cross-feeding between microbes, did not show a specific pattern. However, the energy-loss due to higher excretion in stunted children of these metabolites, which can be used as substrate for the host, is striking. Several microbial taxa also correlated to the intake of macronutrients (including dietary fibre) and energy. Eisenbergiella positively correlated with all macronutrients, while an uncharacterized genus within the Succinivibrionaceae family negatively correlated with all macronutrients. These, and the other correlations observed, may provide indication on how to modulate the gut microbiota of stunted children such that their growth lag can be corrected. Trail registered at https://ichgcp.net/clinical-trials-registry/NCT04698759.

Conflict of interest statement

The authors have declared that no competing interests exist.

Figures

Fig 1. CONSORT flow diagram of the…
Fig 1. CONSORT flow diagram of the cross-sectional study.
Fig 2. Spearman correlation between immune parameters…
Fig 2. Spearman correlation between immune parameters and gut microbiota composition.
Only taxa that are significant (q q to lowest q. Purple: Positive Spearman correlation factor (rho); red: Negative rho.
Fig 3. Spearman correlation between microbial metabolites…
Fig 3. Spearman correlation between microbial metabolites and gut microbiota composition.
Only taxa that are significant (q q to lowest q. A) individual and total SCFA; B) individual and total BCFA. Purple: Positive Spearman correlation factor (rho); red: Negative rho.

References

    1. WHO. Guideline: Assessing and managing children at primary obesity health-care facilities to prevent overweight and malnutrition in the context of the double burden of malnutrition 2017. Available from: .
    1. Osendarp SJM, Brown KH, Neufeld LM, Udomkesmalee E, Moore SE. The double burden of malnutrition-further perspective. Lancet. 2020;396(10254):813. Epub 2020/09/21. doi: 10.1016/S0140-6736(20)31364-7 .
    1. Group" UWWB. Levels and trends in child malnutrition 2018. Available from: .
    1. Thompson DS, Bourdon C, Massara P, Boyne MS, Forrester T, Gonzales GB, et al.. Childhood severe acute malnutrition is associated with metabolic changes in adulthood. JCI Insight. 2020. Epub 2020/11/18. doi: 10.1172/jci.insight.141316 .
    1. Black RE, Victora CG, Walker SP, Bhutta ZA, Christian P, de Onis M, et al.. Maternal and child undernutrition and overweight in low-income and middle-income countries. Lancet. 2013;382(9890):427–51. Epub 2013/06/12. doi: 10.1016/S0140-6736(13)60937-X .
    1. WHO. The WHO Child Growth Standards 2006. Available from: .
    1. Titaley CR, Ariawan I, Hapsari D, Muasyaroh A, Dibley MJ. Determinants of the Stunting of Children Under Two Years Old in Indonesia: A Multilevel Analysis of the 2013 Indonesia Basic Health Survey. Nutrients. 2019;11(5). Epub 2019/05/22. doi: 10.3390/nu11051106 ; PubMed Central PMCID: PMC6567198.
    1. Torlesse H, Cronin AA, Sebayang SK, Nandy R. Determinants of stunting in Indonesian children: evidence from a cross-sectional survey indicate a prominent role for the water, sanitation and hygiene sector in stunting reduction. BMC Public Health. 2016;16:669. Epub 2016/07/31. doi: 10.1186/s12889-016-3339-8 ; PubMed Central PMCID: PMC4966764.
    1. Grantham-McGregor S, Cheung YB, Cueto S, Glewwe P, Richter L, Strupp B, et al.. Developmental potential in the first 5 years for children in developing countries. Lancet. 2007;369(9555):60–70. Epub 2007/01/09. doi: 10.1016/S0140-6736(07)60032-4 ; PubMed Central PMCID: PMC2270351.
    1. Gomez-Gallego C, Garcia-Mantrana I, Martinez-Costa C, Salminen S, Isolauri E, Collado MC. The Microbiota and Malnutrition: Impact of Nutritional Status During Early Life. Annu Rev Nutr. 2019;39:267–90. Epub 2019/08/23. doi: 10.1146/annurev-nutr-082117-051716 .
    1. Kamng’ona AW, Young R, Arnold CD, Kortekangas E, Patson N, Jorgensen JM, et al.. The association of gut microbiota characteristics in Malawian infants with growth and inflammation. Sci Rep. 2019;9(1):12893. Epub 2019/09/11. doi: 10.1038/s41598-019-49274-y ; PubMed Central PMCID: PMC6733848.
    1. Kane AV, Dinh DM, Ward HD. Childhood malnutrition and the intestinal microbiome. Pediatr Res. 2015;77(1–2):256–62. Epub 2014/10/31. doi: 10.1038/pr.2014.179 ; PubMed Central PMCID: PMC4476274.
    1. Surono IS, Widiyanti D, Kusumo PD, Venema K. Gut microbiota profile of Indonesian stunted children and children with normal nutritional status. PLoS One. 2021;16(1):e0245399. Epub 2021/01/27. doi: 10.1371/journal.pone.0245399 ; PubMed Central PMCID: PMC7837488.
    1. Sun M, Wu W, Chen L, Yang W, Huang X, Ma C, et al.. Microbiota-derived short-chain fatty acids promote Th1 cell IL-10 production to maintain intestinal homeostasis. Nat Commun. 2018;9(1):3555. Epub 2018/09/05. doi: 10.1038/s41467-018-05901-2 ; PubMed Central PMCID: PMC6120873.
    1. Sun M, Wu W, Liu Z, Cong Y. Microbiota metabolite short chain fatty acids, GPCR, and inflammatory bowel diseases. J Gastroenterol. 2017;52(1):1–8. Epub 2016/07/28. doi: 10.1007/s00535-016-1242-9 ; PubMed Central PMCID: PMC5215992.
    1. Ferguson A, Humphreys KA, Croft NM. Technical report: results of immunological tests on faecal extracts are likely to be extremely misleading. Clin Exp Immunol. 1995;99(1):70–5. Epub 1995/01/01. doi: 10.1111/j.1365-2249.1995.tb03474.x ; PubMed Central PMCID: PMC1534154.
    1. Kusumo PD, Bela B, Wibowo H, Munasir Z, Surono IS. Lactobacillus plantarum IS-10506 supplementation increases faecal sIgA and immune response in children younger than two years. Benef Microbes. 2019;10(3):245–52. Epub 2019/01/30. doi: 10.3920/BM2017.0178 .
    1. Kusumo PD, Maulahela H, Utari AP, Surono IS, Soebandrio A, Abdullah M. Probiotic Lactobacillus plantarum IS 10506 supplementation increase SCFA of women with functional constipation. Iran J Microbiol. 2019;11(5):389–96. Epub 2020/03/10. ; PubMed Central PMCID: PMC7049320.
    1. Ibrahim MK, Zambruni M, Melby CL, Melby PC. Impact of Childhood Malnutrition on Host Defense and Infection. Clin Microbiol Rev. 2017;30(4):919–71. Epub 2017/08/05. doi: 10.1128/CMR.00119-16 ; PubMed Central PMCID: PMC5608884.
    1. Huus KE, Rodriguez-Pozo A, Kapel N, Nestoret A, Habib A, Dede M, et al.. Immunoglobulin recognition of fecal bacteria in stunted and non-stunted children: findings from the Afribiota study. Microbiome. 2020;8(1):113. Epub 2020/07/29. doi: 10.1186/s40168-020-00890-1 ; PubMed Central PMCID: PMC7385872.
    1. Hamer HM, Jonkers D, Venema K, Vanhoutvin S, Troost FJ, Brummer RJ. Review article: the role of butyrate on colonic function. Aliment Pharmacol Ther. 2008;27(2):104–19. Epub 2007/11/02. doi: 10.1111/j.1365-2036.2007.03562.x .
    1. Verbeke KA, Boobis AR, Chiodini A, Edwards CA, Franck A, Kleerebezem M, et al.. Towards microbial fermentation metabolites as markers for health benefits of prebiotics. Nutr Res Rev. 2015;28(1):42–66. Epub 2015/07/15. doi: 10.1017/S0954422415000037 ; PubMed Central PMCID: PMC4501371.
    1. Wu GD, Chen J, Hoffmann C, Bittinger K, Chen YY, Keilbaugh SA, et al.. Linking long-term dietary patterns with gut microbial enterotypes. Science. 2011;334(6052):105–8. Epub 2011/09/03. doi: 10.1126/science.1208344 ; PubMed Central PMCID: PMC3368382.
    1. Togo AH, Khelaifia S, Bittar F, Maraninchi M, Raoult D, Million M. ’Eisenbergiella massiliensis’, a new species isolated from human stool collected after bariatric surgery. New Microbes New Infect. 2016;13:15–6. Epub 2016/07/01. doi: 10.1016/j.nmni.2016.05.015 ; PubMed Central PMCID: PMC4917486.
    1. Amir I, Bouvet P, Legeay C, Gophna U, Weinberger A. Eisenbergiella tayi gen. nov., sp. nov., isolated from human blood. Int J Syst Evol Microbiol. 2014;64(Pt 3):907–14. Epub 2013/11/28. doi: 10.1099/ijs.0.057331-0 .
    1. Izhak MB, Eshel A, Cohen R, Shapiro LM, Meiri H, Wachtel C, et al.. Projection of gut microbiome pre and post-bariatric surgery to predict surgery outcome preprint on bioRxiv. 2020;2020.08.27.271312; 10.1101/2020.08.27.271312.
    1. Zhang C, Zhang M, Wang S, Han R, Cao Y, Hua W, et al.. Interactions between gut microbiota, host genetics and diet relevant to development of metabolic syndromes in mice. ISME J. 2010;4(2):232–41. Epub 2009/10/30. doi: 10.1038/ismej.2009.112 .
    1. Mancabelli L, Milani C, Lugli GA, Turroni F, Mangifesta M, Viappiani A, et al.. Unveiling the gut microbiota composition and functionality associated with constipation through metagenomic analyses. Sci Rep. 2017;7(1):9879. Epub 2017/08/31. doi: 10.1038/s41598-017-10663-w ; PubMed Central PMCID: PMC5575163.
    1. Vacca M, Celano G, Calabrese FM, Portincasa P, Gobbetti M, De Angelis M. The Controversial Role of Human Gut Lachnospiraceae. Microorganisms. 2020;8(4). Epub 2020/04/25. doi: 10.3390/microorganisms8040573 ; PubMed Central PMCID: PMC7232163.
    1. Li H, Liu F, Lu J, Shi J, Guan J, Yan F, et al.. Probiotic Mixture of Lactobacillus plantarum Strains Improves Lipid Metabolism and Gut Microbiota Structure in High Fat Diet-Fed Mice. Front Microbiol. 2020;11:512. Epub 2020/04/11. doi: 10.3389/fmicb.2020.00512 ; PubMed Central PMCID: PMC7113563.
    1. Duncan SH, Russell WR, Quartieri A, Rossi M, Parkhill J, Walker AW, et al.. Wheat bran promotes enrichment within the human colonic microbiota of butyrate-producing bacteria that release ferulic acid. Environ Microbiol. 2016;18(7):2214–25. Epub 2015/12/05. doi: 10.1111/1462-2920.13158 ; PubMed Central PMCID: PMC4949515.

Source: PubMed

3
Se inscrever