Background Severe acute malnutrition (SAM) among children remains a major health problem in many developing countries. SAM manifests in both an oedematous and a non-oedematous form, with oedematous malnutrition in its most severe form also known as kwashiorkor. The pathogenesis of both types of malnutrition in children remains largely unknown, but gut microbiota (GM) dysbiosis has recently been linked to oedematous malnutrition. In the present study we aimed to assess whether GM composition differed between Ugandan children suffering from either oedematous or non-oedematous malnutrition. Methodology/Principal Findings As part of an observational study among children hospitalized with SAM aged 6–24 months in Uganda, fecal samples were collected at admission. Total genomic DNA was extracted from fecal samples, and PCR amplification was performed followed by Denaturing Gradient Gel Electrophoresis (DGGE) and tag-encoded 16S rRNA gene-targeted high throughput amplicon sequencing. Alpha and beta diversity measures were determined along with ANOVA mean relative abundance and G-test of independence followed by comparisons between groups. Of the 87 SAM children included, 62% suffered from oedematous malnutrition, 66% were boys and the mean age was 16.1 months. GM composition was found to differ between the two groups of children as determined by DGGE (p = 0.0317) and by high-throughput sequencing, with non-oedematous children having lower GM alpha diversity (p = 0.036). However, beta diversity analysis did not reveal larger differences between the GM of children with oedematous and non-oedematous SAM (ANOSIM analysis, weighted UniFrac, R = -0.0085, p = 0.584; unweighted UniFrac, R = 0.0719, p = 0.011). Conclusions/Significance Our results indicate that non-oedematous SAM children have lower GM diversity compared to oedematous SAM children, however no clear compositional differences were identified.
References
[1]
Black R.E., et al., Maternal and child undernutrition and overweight in low-income and middle-income countries. Lancet, 2013. 382(9890): p. 427–51. doi: 10.1016/S0140-6736(13)60937-X. pmid:23746772
[2]
Williams C.D., Oxon B.M., and Lond H., Kwashiorkor: a nutritional disease of children associated with a maize diet. 1935. Bull World Health Organ, 2003. 81(12): p. 912–3. pmid:14997245
[3]
Golden M.H., Golden B.E., and Jackson A.A., Albumin and nutritional oedema. Lancet, 1980. 1(8160): p. 114–6. pmid:6101456 doi: 10.1016/s0140-6736(80)90603-0
[4]
Gopalan C., Kwashiorkor and marasmus: evolution and distinguishing features. 1968. Natl Med J India, 1992. 5(3): p. 145–51. pmid:1306670
[5]
Ciliberto H., et al., Antioxidant supplementation for the prevention of kwashiorkor in Malawian children: randomised, double blind, placebo controlled trial. Bmj, 2005. 330(7500): p. 1109. pmid:15851401 doi: 10.1136/bmj.38427.404259.8f
[6]
Ahmed T., Rahman S., and Cravioto A., Oedematous malnutrition. Indian J Med Res, 2009. 130(5): p. 651–4. pmid:20090122
[7]
Smith M.I., et al., Gut microbiomes of Malawian twin pairs discordant for kwashiorkor. Science, 2013. 339(6119): p. 548–54. doi: 10.1126/science.1229000. pmid:23363771
[8]
Gupta S.S., et al., Metagenome of the gut of a malnourished child. Gut Pathog, 2011. 3: p. 7. doi: 10.1186/1757-4749-3-7. pmid:21599906
[9]
Monira S., et al., Gut microbiota of healthy and malnourished children in bangladesh. Front Microbiol, 2011. 2: p. 228. doi: 10.3389/fmicb.2011.00228. pmid:22125551
[10]
Ghosh T.S., et al., Gut microbiomes of Indian children of varying nutritional status. PLoS One, 2014. 9(4): p. e95547. doi: 10.1371/journal.pone.0095547. pmid:24763225
[11]
Subramanian S., et al., Persistent gut microbiota immaturity in malnourished Bangladeshi children. Nature, 2014. 509(7505): p. 417–21. doi: 10.1038/nature13421
[12]
Humphrey J.H., Child undernutrition, tropical enteropathy, toilets, and handwashing. Lancet, 2009. 374(9694): p. 1032–5. doi: 10.1016/S0140-6736(09)60950-8. pmid:19766883
[13]
Ashworth, A., Guidelines for the inpatient treatment of severely malnourished children. WHO Library Cataloguing-in-Publication Data. 2003.
[14]
World Health Organization, others. Service delivery approaches to HIV testing and conselling (HTC): a strategic HTC programme framework [Internet]. 2012 [cited 2015 Aug 22]. Available from:
[15]
WHO, U., WHO child growth standards and the identification of severe acute malnutrition in infants and children. A Joint Statement. . 2009.
[16]
Qiagen？, S.A.T., QIAamp？ DNA Stool Handbook . Vol. Second Edition. 2012, June.
[17]
Hufeldt M.R., et al., Family relationship of female breeders reduce the systematic inter-individual variation in the gut microbiota of inbred laboratory mice. Lab Anim, 2010. 44(4): p. 283–9. doi: 10.1258/la.2010.010058. pmid:20713427
[18]
Pyndt Jorgensen B., et al., A possible link between food and mood: dietary impact on gut microbiota and behavior in BALB/c mice. PLoS One, 2014. 9(8): p. e103398. doi: 10.1371/journal.pone.0103398. pmid:25133574
[19]
Caporaso J.G., et al., QIIME allows analysis of high-throughput community sequencing data. Nat Methods, 2010. 7(5): p. 335–6. doi: 10.1038/nmeth.f.303. pmid:20383131
[20]
Edgar R.C., et al., UCHIME improves sensitivity and speed of chimera detection. Bioinformatics, 2011. 27(16): p. 2194–200. doi: 10.1093/bioinformatics/btr381. pmid:21700674
[21]
McDonald D., et al., An improved Greengenes taxonomy with explicit ranks for ecological and evolutionary analyses of bacteria and archaea. Isme j, 2012. 6(3): p. 610–8. doi: 10.1038/ismej.2011.139. pmid:22134646
[22]
Rytter M.J., et al., Social, dietary and clinical correlates of oedema in children with severe acute malnutrition: a cross-sectional study. BMC Pediatr, 2015. 15(1): p. 25. doi: 10.1186/s12887-015-0341-8
[23]
De Filippo C., et al., Impact of diet in shaping gut microbiota revealed by a comparative study in children from Europe and rural Africa. Proc Natl Acad Sci U S A, 2010. 107(33): p. 14691–6. doi: 10.1073/pnas.1005963107. pmid:20679230
[24]
Mutlu E.A., et al., A compositional look at the human gastrointestinal microbiome and immune activation parameters in HIV infected subjects. PLoS Pathog, 2014. 10(2): p. e1003829. doi: 10.1371/journal.ppat.1003829. pmid:24586144
[25]
Lauber et al., Effect of storage conditions on the assessment of bacterial community structure in soil and human-associated samples (2010), FEMS Microbiol. Letters 307:80–86 doi: 10.1111/j.1574-6968.2010.01965.x
[26]
Allen S.J., et al., Probiotics for treating infectious diarrhoea. Cochrane Database Syst Rev, 2004(2): p. Cd003048. pmid:15106189 doi: 10.1002/14651858.cd003048.pub3
[27]
Kerac M., et al., Probiotics and prebiotics for severe acute malnutrition (PRONUT study): a double-blind efficacy randomised controlled trial in Malawi. Lancet, 2009. 374(9684): p. 136–44. doi: 10.1016/S0140-6736(09)60884-9. pmid:19595348
