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Cited by 1,270Gut microbiota and healthChild Nutrition and Water AccessInfant Nutrition and Health

Persistent gut microbiota immaturity in malnourished Bangladeshi children

Open access
Subramanian, Sathish, Huq, Sayeeda, Yatsunenko, Tanya, Haque, Rashidul, Mahfuz, Mustafa, Alam, Mohammed A., Benezra, Amber, DeStefano, Joseph +9 more·2014·Nature
DOI 10.1038/nature13421PMC PMC4189846
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Abstract

Therapeutic food interventions have reduced mortality in children with severe acute malnutrition (SAM), but incomplete restoration of healthy growth remains a major problem. The relationships between the type of nutritional intervention, the gut microbiota, and therapeutic responses are unclear. In the current study, bacterial species whose proportional representation define a healthy gut microbiota as it assembles during the first two postnatal years were identified by applying a machine-learning-based approach to 16S ribosomal RNA data sets generated from monthly faecal samples obtained from birth onwards in a cohort of children living in an urban slum of Dhaka, Bangladesh, who exhibited consistently healthy growth. These age-discriminatory bacterial species were incorporated into a model that computes a ‘relative microbiota maturity index’ and ‘microbiota-for-age Z-score’ that compare postnatal assembly (defined here as maturation) of a child’s faecal microbiota relative to healthy children of similar chronologic age. The model was applied to twins and triplets (to test for associations of these indices with genetic and environmental factors, including diarrhoea), children with SAM enrolled in a randomized trial of two food interventions, and children with moderate acute malnutrition. Our results indicate that SAM is associated with significant relative microbiota immaturity that is only partially ameliorated following two widely used nutritional interventions. Immaturity is also evident in less severe forms of malnutrition and correlates with anthropometric measurements. Microbiota maturity indices provide a microbial measure of human postnatal development, a way of classifying malnourished states, and a parameter for judging therapeutic efficacy. More prolonged interventions with existing or new therapeutic foods and/or addition of gut microbes may be needed to achieve enduring repair of gut microbiota immaturity in childhood malnutrition and improve clinical outcomes.

AI snapshot

Written from the paper’s full text.

TL;DR

A machine-learning model based on age-discriminatory fecal bacterial taxa defines gut microbiota maturation in healthy Bangladeshi children and shows that severe acute malnutrition (SAM) is associated with marked microbiota immaturity that is only partially and transiently improved by two food interventions. The same immaturity is seen in moderate acute malnutrition and correlates with anthropometric status.

Key findings

  • A Random Forests model using the top 24 age-discriminatory 97% ID OTUs explained 73% of variance in chronologic age in healthy Bangladeshi children and generalized to independent healthy singleton and twin/triplet validation sets (r² = 0.71 and 0.68, respectively).
  • In 64 children with SAM (mean enrollment WHZ −4.2 ± 0.7), relative microbiota maturity and microbiota-for-age Z-scores were significantly lower than in healthy children at enrollment and end of nutritional rehabilitation (Dunnett’s p < 0.0001 for both treatment groups); improvements after RUTF or Khichuri-Halwa were not durable, with regression to significant immaturity beyond 4 months after treatment stopped.
  • RUTF and Khichuri-Halwa did not differ significantly in weight gain (10.9 ± 4.6 vs 10.4 ± 5.4 g/kg/day; p = 0.7), and WHZ remained lower than healthy children during follow-up (−2.1 ± 1.2 Khichuri-Halwa; −2.4 ± 0.8 RUTF vs −0.5 ± 1.1 healthy; p < 0.0001).
  • In a cross-sectional analysis at 18 months, children with MAM had significantly lower relative microbiota maturity and MAZ scores than healthy children, and these metrics correlated with WHZ (Spearman rho = 0.62 and 0.63; p < 0.001); 220 bacterial taxa differed in SAM vs healthy, with 165 significantly diminished during longer-term follow-up in both treatment groups.

Methods

  • Healthy Bangladeshi birth cohorts in Mirpur, Dhaka: 50 children followed monthly for up to ~24 months (25 singletons, 11 twin pairs, 1 triplet set; 996 fecal samples), plus twins/triplets for validation; SAM trial enrolled 64 children aged 6–20 months randomized to imported RUTF (Plumpy’Nut) or locally produced Khichuri-Halwa; MAM analysis used 33 children at 18 months.
  • Fecal bacterial communities were profiled by V4-16S rRNA sequencing (1,897 fecal DNA samples total; 1,222 97% ID OTUs passing detection filters), with Random Forests regression against chronologic age to identify age-discriminatory taxa and a sparse 24-taxon model to compute relative microbiota maturity and microbiota-for-age Z-score.
  • Associations with clinical/dietary factors used linear mixed models, Dunnett’s post-hoc comparisons, Spearman correlations, and Mann-Whitney/Wilcoxon tests; antibiotic effects were assessed in a subset of nine children with pre-antibiotic samples.

Limitations

  • The paper states that most children with SAM could not provide fecal samples before antibiotics, so effects of other antibiotics consumed singly or in combinations could not be measured; it also notes that functional roles of age-discriminatory taxa need clarification and that more clinical studies are needed to test whether microbiota immaturity persists beyond childhood.
  • The paper notes that systematic analyses across different populations may show a need for geographic specificity when constructing microbiota-based models or diagnostics.
  • Evident from the text: the main findings are associational, sample sizes for some subgroups are small (e.g., nine children with pre-antibiotic samples; 10 children with MAM), and treatment effects on microbiota maturity were not durable, limiting conclusions about causality or long-term therapeutic repair.

Model-written summary. Check it against the paper before relying on it.

Integrity signals

Registry

Crossref · 10.1038/nature13421

Cites

26 of 26 references verified0 citation errors · 0 not checkable

Statistics

Nothing to recompute.

Claims the paper makes

0 of 25 cited sources checked · 0 supported · 0 flagged

  • Findingown data

    Gut microbiota immaturity is also present in less severe malnutrition.

    “Immaturity is also evident in less severe forms of malnutrition and correlates with anthropometric measurements.”
    Quote in the paperSubstantial claim
  • Findingown data

    Severe acute malnutrition is associated with substantial relative gut microbiota immaturity.

    “Our results indicate that SAM is associated with significant relative microbiota immaturity that is only partially ameliorated following two widely used nutritional interventions.”
    Quote in the paperSubstantial claim
  • Findingown data

    The Random Forests regression of 1222 OTU relative abundances against chronologic age explained 73% of the variance in age.

    “The regression explained 73% of the variance related to chronologic age.”
    Quote in the paperSubstantial claim
  • Findingown data

    Adding taxa beyond the top 24 produced minimal improvement in predictive performance.

    “Minimal improvement in predictive performance was observed when including taxa beyond the top 24”
    Quote in the paperSubstantial claim
  • Findingown data

    The sparse model generalized to two additional healthy groups, with r2 values of 0.71 and 0.68.

    “The model was found to be generalizable to both groups, (r2 = 0.71 and 0.68, respectively)”
    Quote in the paperSubstantial claim
  • The quote only partly states this claim. 5
  • May combine two claims. 21
  • Classified as probably not a substantial claim. 19

  • The quote only partly states this claim.

    Findingown data

    The relative gut microbiota immaturity in severe acute malnutrition is only partially improved by two widely used nutritional interventions.

    “improvement in this metric was short-lived for the RUTF and Khichuri-Halwa groups, with regression to significant immaturity relative to healthy children beyond four months after treatment was stopped”
    Quote in the paperSubstantial claim

  • May combine two claims.

    Findingown data

    Monozygotic twins were not significantly more correlated in maturity profiles than dizygotic twins, and within the triplet set the monozygotic siblings were not more correlated than the fraternal sibling.

    “Monozygotic (MZ) twins were not significantly more correlated in their maturity profiles compared to dizygotic (DZ) twins, and within the set of triplets, the two MZ siblings were not more correlated than their fraternal sibling”
    Quote in the paperSubstantial claim

  • May combine two claims.

    Findingown data

    In a cross-sectional sample of 33 18-month-old children above and below the MAM threshold, WHZ scores are significantly inversely correlated with relative microbiota maturity and MAZ scores (Spearman rho = 0.62 and 0.63, p < 0.001).

    “WHZ scores are significantly inversely correlated with relative microbiota maturity (panel a) and MAZ scores (panel b) in a cross-sectional analysis of 33 children at 18 months of age who were above and below the anthropometric threshold for MAM (Spearman rho = 0.62 and 0.63, respectively; ***, p < 0.001).”
    Quote in the paperSubstantial claim

  • May combine two claims.

    Findingown data

    In the Khichuri-Halwa group, relative microbiota maturity and MAZ scores improved after treatment but later regressed, with significant differences from healthy children at 2-3 months and more than 4 months after treatment cessation.

    “In the Khichuri-Halwa group, relative microbiota maturity and MAZ scores improved following treatment, but subsequently regressed, exhibiting significant differences relative to healthy children at 2-3 months, and >4 months after cessation of treatment”
    Quote in the paperSubstantial claim

  • The quote only partly states this claim.

    Findingown data

    In healthy twins/triplets, diarrhea has a significant negative effect on age-adjusted SDI (effect -0.44, p=0.0028).

    “Diarrhea | -0.44 | 0.15 | 0.0028”
    Quote in the paperNot a substantial claim

  • May combine two claims.

    Findingown data

    The lower bacterial diversity seen in SAM remained after Khichuri-Halwa and improved only briefly with RUTF.

    “The reduced bacterial diversity associated with SAM persisted after Khichuri-Halwa and only transiently improved with RUTF”
    Quote in the paperSubstantial claim

  • The quote only partly states this claim.

    Findingown data

    In healthy twins/triplets, month following diarrhea has a significant negative effect on age-adjusted SDI (effect -0.37, p=0.0247).

    “Month following Diarrhea | -0.37 | 0.16 | 0.0247”
    Quote in the paperNot a substantial claim

  • May combine two claims.

    Findingown data

    Children with MAM had significantly lower relative microbiota maturity, lower MAZ scores, and differences in relative abundances of age-discriminatory taxa compared with healthy children.

    “Comparing children with MAM to those defined as healthy revealed significantly lower relative microbiota maturity, MAZ scores and differences in the relative abundances of age-discriminatory taxa in the malnourished group”
    Quote in the paperSubstantial claim

  • May combine two claims.

    Findingown data

    220 bacterial taxa differed significantly in proportional representation between SAM and healthy children, and 165 of these were significantly diminished in SAM during longer-term follow-up in both treatment groups.

    “We identified a total of 220 bacterial taxa that were significantly different in their proportional representation in the fecal microbiota of children with SAM compared to healthy; 165 of these 220 97%ID OTUs were significantly diminished in the microbiota of children with SAM during the longer term follow-up period in both treatment groups”
    Quote in the paperSubstantial claim

  • Probably not a substantial claim: may not pass S3 (load-bearing).

    Findingown data

    Three of the 97% ID OTUs enriched in mothers' first month postpartum are members of the top 24 age-discriminatory taxa and belong to the genus Bifidobacterium.

    “Three of these 97%ID OTUs are members of the top 24 age-discriminatory taxa (blue) and belong to the genus Bifidobacterium.”
    Quote in the paperNot a substantial claim

  • Probably not a substantial claim: may not pass S3 (load-bearing).

    Findingown data

    The relative abundances of Streptococcaceae and Enterobacteriaceae changed in opposite directions.

    “opposing changes in the relative abundance of Streptococcaceae and Enterobacteriaceae were readily apparent”
    Quote in the paperNot a substantial claim

  • May combine two claims. The quote only partly states this claim.

    Findingown data

    During post-intervention follow-up in the SAM trial, antibiotic usage and diarrhea are not significantly associated with relative microbiota maturity, MAZ, or SDI in either intervention arm (all p>0.05).

    “Antibiotics | RUTF | -0.37 | 0.81 | 0.65”
    Quote in the paperNot a substantial claim

  • May combine two claims.

    Findingown data

    Microbiota maturity was significantly lower in fecal samples collected during and one month after diarrheal episodes, but not after that period.

    “Maturity was significantly decreased in fecal samples obtained during and one month following diarrheal episodes (p<0.001 and p<0.01 respectively) but not beyond that period”
    Quote in the paperNot a substantial claim

  • May combine two claims.

    Findingown data

    Compared with healthy children, SAM was associated with significant microbiota immaturity at the start and at the end of nutritional rehabilitation.

    “compared to healthy, SAM was associated with significant microbiota immaturity at the time that nutritional rehabilitation was initiated and at cessation of treatment (Dunnett’s post-hoc test, p<0.0001 for both groups; Fig. 2b)”
    Quote in the paperSubstantial claim

  • May combine two claims.

    Findingown data

    Microbiota maturity and MAZ scores were significantly correlated with WHZ (Spearman rho=0.62 and 0.63; p<0.001).

    “The relationship between microbiota maturity, MAZ scores and WHZ was significant (Spearman rho=0.62 and 0.63; p<0.001, respectively; Extended Data Fig. 9a,b).”
    Quote in the paperSubstantial claim

  • May combine two claims.

    Findingown data

    Preantibiotic samples and samples collected at the end of all treatment interventions did not differ significantly in microbiota maturity, bacterial diversity, or WHZ scores.

    “When preantibiotic fecal samples from these nine children were compared to samples collected at the end of all treatment interventions (dietary and antibiotic, 20±9d after admission), no significant differences in microbiota maturity (p=0.7, Wilcoxon), bacterial diversity (or WHZ scores) were found”
    Quote in the paperSubstantial claim

  • Probably not a substantial claim: may not pass S3 (load-bearing).

    Findingown data

    At enrollment, the SAM children's mean WHZ was -4.2±0.7.

    “At enrollment, WHZ scores averaged -4.2±0.7 (mean±SD)”
    Quote in the paperNot a substantial claim

  • Probably not a substantial claim: may not pass S3 (load-bearing).

    Findingown data

    In healthy twins/triplets, formula in diet has a significant positive effect on MAZ (effect +0.22, p=0.04).

    “Formula | +0.22 | 0.11 | 0.04”
    Quote in the paperNot a substantial claim

  • Probably not a substantial claim: may not pass S3 (load-bearing). May combine two claims.

    Findingown data

    The number of diarrheal episodes per year per child and the number of diarrheal days per year per child did not differ significantly between the singleton training and validation sets.

    “There were no significant differences in the number of diarrheal episodes/year/child and the number of diarrheal days/year/child between the singleton training and validation sets (Student’s t-test, p=0.5).”
    Quote in the paperNot a substantial claim

  • May combine two claims. The quote only partly states this claim.

    Findingown data

    In the SAM trial, relative microbiota maturity, MAZ, and SDI are significantly lower than healthy controls at enrollment, during, and end of intervention in both RUTF and Khichuri-Halwa arms (p<0.001).

    “Enrollment | RUTF | -5.62 | 0.78 | <0.001”
    Quote in the paperSubstantial claim

  • May combine two claims.

    Findingown data

    Children with MAM have significantly lower relative microbiota maturity and MAZ scores than healthy children.

    “Children with MAM (WHZ scores lower than -2 SD; grey) have significantly lower relative microbiota maturity (panel a) and MAZ scores (panel b) than healthy individuals (blue).”
    Quote in the paperSubstantial claim

  • May combine two claims.

    Findingown data

    In healthy twins/triplets, postnatal age, solid foods, exclusive breastfeeding, enteropathogen detected by microscopy, antibiotics, and other periods relative to diarrhea have no significant effect on relative microbiota maturity.

    “The factors ‘postnatal age’, ‘presence/absence of solid foods’,‘exclusive breastfeeding’, ‘enteropathogen detected by microscopy’, ‘antibiotics’ as well as ‘other periods relative to diarrhea’ had no significant effect.”
    Quote in the paperNot a substantial claim

  • Probably not a substantial claim: may not pass S3 (load-bearing).

    Premisecitation

    Long-term efficacy of nutritional interventions for MAM is similarly unclear.

    “There is similar lack of clarity about the long-term efficacy of nutritional interventions for MAM7,8.”
    Quote in the paperNot a substantial claim0 of 2 sources checked
    • cites [7] Lazzerini, M., Rubert, L. & Pani, P. Specially formulated foods for treating children with moderate acute malnutrition in low- and middle-income countries. Cochrane Database Syst. Rev. CD009584 (2013) source

      Not checked in the free run.

    • cites [8] Prentice, A. M. et al. Critical windows for nutritional interventions against stunting. Am. J. Clin. Nutr. 97, 911–918 (2013) source

      Not checked in the free run.

  • May combine two claims.

    Premisecitation

    Therapeutic food interventions lower mortality in severe acute malnutrition, but healthy growth is not fully restored, which remains a major problem.

    “Therapeutic food interventions have reduced mortality in children with severe acute malnutrition (SAM) but incomplete restoration of healthy growth remains a major problem1,2.”
    Quote in the paperSubstantial claim0 of 2 sources checked
    • cites [1] Ahmed, T. et al. Mortality in severely malnourished children with diarrhoea and use of a standardised management protocol. Lancet 353, 1919–1922 (1999) source

      Not checked in the free run.

    • cites [2] Ashraf, H. et al. A follow-up experience of 6 months after treatment of children with severe acute malnutrition in Dhaka, Bangladesh. J. Trop. Pediatr. 58, 253–257 (2012) source

      Not checked in the free run.

  • Probably not a substantial claim: may not pass S3 (load-bearing).

    Premisecitation

    The extent to which the standardized protocol restores normal growth and development over the long term remains to be determined by longitudinal studies.

    “although the extent to which this protocol results in long-term restoration of normal growth and development needs to be ascertained through longitudinal studies5,6”
    Quote in the paperNot a substantial claim0 of 2 sources checked
    • cites [5] Ahmed, T. & Begum, B. Badiuzzaman, Ali, M. & Fuchs, G. Management of severe malnutrition and diarrhea. Indian J. Pediatr. 68, 45–51 (2001) source

      Not checked in the free run.

    • cites [6] Ahmed, T. et al. P0580 Use of a standardized protocol based on local diet results in satisfactory rates of weight gain of severely malnourished children undergoing nutritional rehabilitation. J. Pediatr. Gastroenterol. Nutr. 39, S277 (2004) source

      Not checked in the free run.

  • May combine two claims.

    Interpretationreasoning

    Microbiota maturity indices offer a microbial measure of human postnatal development, a way to classify malnourished states, and a parameter for judging therapeutic efficacy.

    “Microbiota maturity indices provide a microbial measure of human postnatal development, a way of classifying malnourished states, and a parameter for judging therapeutic efficacy.”
    Quote in the paperSubstantial claim

  • Probably not a substantial claim: may not pass S3 (load-bearing).

    Premisecitation

    Bangladesh has a standardized protocol for treating SAM and its complications.

    “A standardized treatment protocol for SAM and its complications has been developed in Bangladesh1.”
    Quote in the paperNot a substantial claim0 of 1 sources checked
    • cites [1] Ahmed, T. et al. Mortality in severely malnourished children with diarrhoea and use of a standardised management protocol. Lancet 353, 1919–1922 (1999) source

      Not checked in the free run.

  • May combine two claims.

    Premisecitation

    Food is a major determinant of the proportional representation of organisms in the gut microbiota and of its gene content.

    “Food is a major factor that shapes the proportional representation of organisms present in the gut microbial community (microbiota), and its gene content (microbiome).”
    Quote in the paperSubstantial claim0 of 6 sources checked
    • cites [9] Muegge, B. D. et al. Diet drives convergence in gut microbiome functions across mammalian phylogeny and within humans. Science 332, 970–974 (2011) source

      Not checked in the free run.

    • cites [10] Wu, G. D. et al. Linking long-term dietary patterns with gut microbial enterotypes. Science 334, 105–108 (2011) source

      Not checked in the free run.

    • cites [11] Yatsunenko, T. et al. Human gut microbiome viewed across age and geography. Nature 486, 222–227 (2012) source

      Not checked in the free run.

    • cites [12] Smith, M. I. et al. Gut microbiomes of Malawian twin pairs discordant for kwashiorkor. Science 339, 548–554 (2013) source

      Not checked in the free run.

    • cites [13] David, L. A. et al. Diet rapidly and reproducibly alters the human gut microbiome. Nature 505, 559–563 (2014) source

      Not checked in the free run.

    • cites [14] Tang, W. H. W. et al. Intestinal microbial metabolism of phosphatidylcholine and cardiovascular risk. N. Engl. J. Med. 368, 1575–1584 (2013) source

      Not checked in the free run.

  • Probably not a substantial claim: may not pass S3 (load-bearing).

    Premisecitation

    The gut microbiota and microbiome help extract and metabolize dietary ingredients.

    “The microbiota/microbiome in turn plays an important role in extracting and metabolizing dietary ingredients9-14.”
    Quote in the paperNot a substantial claim0 of 6 sources checked
    • cites [9] Muegge, B. D. et al. Diet drives convergence in gut microbiome functions across mammalian phylogeny and within humans. Science 332, 970–974 (2011) source

      Not checked in the free run.

    • cites [10] Wu, G. D. et al. Linking long-term dietary patterns with gut microbial enterotypes. Science 334, 105–108 (2011) source

      Not checked in the free run.

    • cites [11] Yatsunenko, T. et al. Human gut microbiome viewed across age and geography. Nature 486, 222–227 (2012) source

      Not checked in the free run.

    • cites [12] Smith, M. I. et al. Gut microbiomes of Malawian twin pairs discordant for kwashiorkor. Science 339, 548–554 (2013) source

      Not checked in the free run.

    • cites [13] David, L. A. et al. Diet rapidly and reproducibly alters the human gut microbiome. Nature 505, 559–563 (2014) source

      Not checked in the free run.

    • cites [14] Tang, W. H. W. et al. Intestinal microbial metabolism of phosphatidylcholine and cardiovascular risk. N. Engl. J. Med. 368, 1575–1584 (2013) source

      Not checked in the free run.

  • Probably not a substantial claim: may not pass S3 (load-bearing).

    Premisecitation

    SAM and MAM usually arise between three and 24 months of age.

    “SAM and MAM typically develop between three and 24 months of life4.”
    Quote in the paperNot a substantial claim0 of 1 sources checked
    • cites [4] Victora, C. G., de Onis, M., Hallal, P. C., Blössner, M. & Shrimpton, R. Worldwide timing of growth faltering: revisiting implications for interventions. Pediatrics 125, e473–e480 (2010) source

      Not checked in the free run.

  • Probably not a substantial claim: may not pass S3 (load-bearing).

    Study design and conductown data

    Internal control mock communities were run alongside the Illumina MiSeq samples.

    “‘Mock’ communities, consisting of mixtures of DNAs isolated from 48 sequenced members of the human gut microbiota combined in one equivalent and two intentionally varied combinations, were included as internal controls in the Illumina MiSeq runs.”
    Quote in the paperNot a substantial claim

  • Probably not a substantial claim: may not pass S3 (load-bearing).

    Study design and conductnone given

    The SAM trial was registered as clinical trial NCT01331044.

    “clinical trial NCT01331044”
    Quote in the paperNot a substantial claim

  • Probably not a substantial claim: may not pass S3 (load-bearing). May combine two claims.

    Study design and conductnone given

    Washington University and icddr,b IRBs approved the anthropologic survey.

    “This survey, approved by the Washington University and icddr,b IRBs”
    Quote in the paperNot a substantial claim

  • Probably not a substantial claim: may not pass S3 (load-bearing). May combine two claims.

    Premisecitation

    Prior epidemiological work links MAM episodes to later SAM and to stunting.

    “Epidemiological studies indicate that periods of MAM are associated with progression to SAM, and with stunting which affects >40% of children under the age of five in Bangladesh17.”
    Quote in the paperNot a substantial claim0 of 1 sources checked
    • cites [17] Dewey, K. G. et al. Infant weight-for-length is positively associated with subsequent linear growth across four different populations. Matern. Child Nutr. 1, 11–20 (2005) source

      Not checked in the free run.

  • Probably not a substantial claim: may not pass S3 (load-bearing).

    Study design and conductown data

    The study could not measure the effects of other antibiotics, taken alone or in combinations, on microbiota maturation metrics in children who could not provide pre-intervention fecal samples.

    “we could not, in cases where children were not able to provide pre-intervention fecal samples, measure the effects of other antibiotics, consumed singly or in various combinations, on their metrics of microbiota maturation”
    Quote in the paperNot a substantial claim

  • Probably not a substantial claim: may not pass S3 (load-bearing).

    Study design and conductown data

    Mock-community data supported diversity and precision-sensitivity analyses.

    “Data from the mock communities were used for diversity and precisionsensitivity analyses employing methods described previously15,23.”
    Quote in the paperNot a substantial claim0 of 2 sources checked
    • cites [15] Faith, J. J. et al. The long-term stability of the human gut microbiota. Science 341, (2013) source

      Not checked in the free run.

    • cites [23] Bokulich, N. A. et al. Quality-filtering vastly improves diversity estimates from Illumina amplicon sequencing. Nature Meth. 10, 57–59 (2013) source

      Not checked in the free run.

  • Probably not a substantial claim: may not pass S3 (load-bearing).

    Study design and conductown data

    Plasma DNA and 96 polymorphic SNPs were used to establish twin and triplet zygosity.

    “The zygosity of twin pairs and triplets was determined using plasma DNA and a panel of 96 polymorphic SNPs (Center for Inherited Disease Research, Johns Hopkins University).”
    Quote in the paperNot a substantial claim

  • Classified as probably not a substantial claim. May combine two claims.

    Study design and conductown data

    The sparse model was trained on 12 healthy singletons (272 fecal samples) and validated in other healthy children without further parameter optimization.

    “A sparse model consisting of the top 24 taxa was then trained on the training set of 12 healthy singletons (272 fecal samples). Without any further parameter optimization, this model was validated in other healthy children (13 singletons, 25 twins and triplets) and then applied to samples in children with SAM and MAM.”
    Quote in the paperSubstantial claim

  • Probably not a substantial claim: may not pass S3 (load-bearing).

    Study design and conductown data

    Children with SAM were randomly assigned to the RUTF or Khichuri-Halwa treatment arm.

    “Children ranged in age from 6 to 20 months of age at the time of enrollment and were randomly assigned to either of the treatment arms.”
    Quote in the paperNot a substantial claim
39 of 39

  • The paper relies on this without support.

    The relationships among nutritional intervention type, gut microbiota, and therapeutic responses are unclear.

    “The relationships between the type of nutritional intervention, the gut microbiota, and therapeutic responses are unclear.”
1 of 1

Claims other papers make about this one

Each is checked against this paper’s own text: does it say what the citing paper says it does?

  • Children in an urban slum in Bangladesh with moderate or severe acute malnutrition had an 'immature' gut microbiota, with discriminatory taxa more similar to younger rather than age-matched healthy individuals from the same location.

    “a sample of children living in an urban slum in Bangladesh with either moderate acute malnutrition or severe acute malnutrition had a gut microbiota that was ‘immature’; meaning discriminatory taxa in their gut communities were more similar to younger rather than age-matched healthy individuals from the same location [165].”

    From The athletic gut microbiota (2020) · cites this paper as [165]

  • The 'immaturity' of the gut microbiota was greater in more severely malnourished children, with probable physiologic, metabolic, and immunologic consequences.

    “This ‘immaturity’ was greater in those more severely malnourished with probable physiologic, metabolic, and immunologic consequences [165].”

    From The athletic gut microbiota (2020) · cites this paper as [165]

Self-check

Percentages, sums and reported differences re-computed from the paper’s own numbers.

Each contradiction between two passages listed here was confirmed by an independent check.

  • Claim of improvement within one month conflicts with Khichuri-Halwa result

    Major

    The text says both groups improved significantly within one month, but Table ED14 reports no significant change from enrollment in relative microbiota maturity for the Khichuri-Halwa group at that time (p=0.76). Its MAZ comparison is also nonsignificant (p=0.20).

  • Positive correlations are described as inverse

    Minor

    The caption calls the correlations between WHZ and both microbiota maturity measures inverse, but reports positive Spearman coefficients for both.

2 of 2

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Authors
Subramanian, S., Huq, S., Yatsunenko, T., Haque, R., Mahfuz, M., Alam, M. A., Benezra, A., DeStefano, J., Meier, M. F., Muegge, B. D., Barratt, M. J., VanArendonk, L. G., Zhang, Q., Province, M. A., Petri Jr, W. A., Ahmed, T., & Gordon, J. I.
Affiliations
  • Washington University in St. Louis (US)
  • International Centre for Diarrhoeal Disease Research (BD)
  • The New School (US)
Corresponding author
Gordon, Jeffrey I.
ORCID
Venue
Nature
Publisher
Springer Science and Business Media LLC
Published
2014-06
Volume
510
Issue
7505
Pages
417-421
ISSN
  • 0028-0836 (ISSN-L)
  • 1476-4687
DOI
10.1038/nature13421
PMC
PMC4189846
OpenAlex
W2151241623
Semantic Scholar
2322f52fd0751c363caa63b546dc30848772f2e3
Cited by
1,270
References
28
Citations by year
2026: 83 · 2025: 91 · 2024: 101 · 2023: 118 · 2022: 126 · 2021: 159 · 2020: 131 · 2019: 101 · 2018: 89 · 2017: 87 · 2016: 94 · 2015: 66 · 2014: 23
FWCI
36.93
Type
journal article
Language
en
Open access
Licence
www.springer.com/tdm (tdm)
Locations
  • Nature (publishedVersion)
  • PubMed (publishedVersion)
  • PubMed Central (acceptedVersion)
  • RePEc: Research Papers in Economics (submittedVersion)
Funders
  • International Atomic Energy Agency
  • National Institute of General Medical Sciences (T32GM007067)
  • National Institute of Allergy and Infectious Diseases (AI 043596, R01AI043596)
Topics
  • Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Gut microbiota and health
  • Health Sciences › Nursing › Nutrition and Dietetics › Child Nutrition and Water Access
  • Health Sciences › Nursing › Nutrition and Dietetics › Infant Nutrition and Health
Keywords
gut microbiota, severe acute malnutrition, child malnutrition, food-based interventions, probiotics, prebiotics, fecal microbiota transplantation, diarrhea, twins and triplets, Bangladesh, low-income countries, 16S rRNA
MeSH terms
Bacteria, Bangladesh, Feces, Female, Humans, Infant, Infant Nutrition Disorders, Male, Models, Biological, Nutritional Status, RNA, Ribosomal, 16S, Bacterial Physiological Phenomena, Gastrointestinal Tract, Biodiversity, Microbiota

About these checks

Registry, retraction, Cites and statistics results are computed, not judged, with one exception: a printed reference that no index lists is read once by a model before it counts as a citation error. Claims are extracted by a model and kept only when their quote appears verbatim in the text; each cited source is then checked, with a model’s help, for whether it says what the claim relies on. Those verdicts can be wrong — read the claim’s quote and the cited source before relying on one.

Claims read by deepseek-v4.1-flash under definition version 3 (extract-v3) on 2026-10-08.

Classified by jev-1.13-20260917 (gold-guideline-v0.2) on 2026-10-08.

Statistics and arithmetic are recomputed, not judged.

Confidence bands are shown only for fields calibrated on our annotated test set. None is calibrated yet, so no band is shown.

What counts as a claim ›How we measure confidence ›How we check this ›

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