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Persistent gut microbiota immaturity in malnourished Bangladeshi children
Open accessAbstract
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.
Overview
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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.
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66 Own result · 11 Not checked yet · 8 Own method · 5 Own interpretation
A result the paper reports from its own data — it cites no other source for it, so there is none to check. The quote shows it is in the paper.
In the paper
“Immaturity is also evident in less severe forms of malnutrition and correlates with anthropometric measurements.”
§ Persistent Gut Microbiota Immaturity in Malnourished Bangladeshi Children > Abstract
plain- Asserted: passes — The authors put it forward as true.
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In the paper
“Our results indicate that SAM is associated with significant relative microbiota immaturity that is only partially ameliorated following two widely used nutritional interventions.”
§ Persistent Gut Microbiota Immaturity in Malnourished Bangladeshi Children > Abstract
hedgedcorrelational- Asserted: passes — The authors put it forward as true.
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In the paper
“The regression explained 73% of the variance related to chronologic age.”
§ Persistent Gut Microbiota Immaturity in Malnourished Bangladeshi Children > Abstract
plaincorrelationaln = 12- Asserted: passes — The authors put it forward as true.
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In the paper
“Minimal improvement in predictive performance was observed when including taxa beyond the top 24”
§ Persistent Gut Microbiota Immaturity in Malnourished Bangladeshi Children > Abstract
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In the paper
“The model was found to be generalizable to both groups, (r2 = 0.71 and 0.68, respectively)”
§ Persistent Gut Microbiota Immaturity in Malnourished Bangladeshi Children > Abstract
plaincorrelationaln = 25- Asserted: passes — The authors put it forward as true.
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In the paper
“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 rRNA datasets generated from monthly fecal samples obtained from a birth-cohort of children”
§ Persistent Gut Microbiota Immaturity in Malnourished Bangladeshi Children > Abstract
plaincorrelational- Asserted: passes — The authors put it forward as true.
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In the paper
“Immaturity is also evident in less severe forms of malnutrition and correlates with anthropometric measurements.”
§ Persistent Gut Microbiota Immaturity in Malnourished Bangladeshi Children > Abstract
plaincorrelational- Asserted: passes — The authors put it forward as true.
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In the paper
“expansion of our sparse model from 24 to 60 taxa yielded similar results regarding the effects of diarrhea in healthy individuals, MAM and SAM (and its treatment with RUTF and Khichuri-Halwa) on microbiota maturity”
§ Persistent Gut Microbiota Immaturity in Malnourished Bangladeshi Children > Prospectus
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In the paper
“The fraction of fecal samples collected from each child where oral antibiotics had been consumed within the prior 7 days was not significantly different between the training and two validation sets (p=0.14; one-way ANOVA; see Extended Data Table 4).”
§ Persistent Gut Microbiota Immaturity in Malnourished Bangladeshi Children > Methods > Twins/Triplets birth cohort
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In the paper
“Linear mixed models of these specified environmental factors indicated that ‘diarrhea’, ‘month following diarrhea’ and ‘presence of formula in diet’ have significant effects on relative microbiota maturity, accounting for random effects arising from within-family and within-child dependence in measurements of this maturity metric.”
- Also stated in: § Extended Data · plain
“Diarrhea | -1.98 | 0.51 | 0.0001”
§ Persistent Gut Microbiota Immaturity in Malnourished Bangladeshi Children > Extended Data
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- Also stated in: § Extended Data · plain
- The quote only partly states this claim. 5
- It may state two separate claims as one. 21
- Probably not a substantial claim. 19
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In the paper
“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”
§ Persistent Gut Microbiota Immaturity in Malnourished Bangladeshi Children > The effects of SAM on microbiota maturity
plaindirect- Asserted: passes — The authors put it forward as true.
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In the paper
“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”
§ Persistent Gut Microbiota Immaturity in Malnourished Bangladeshi Children > Abstract
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In the paper
“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).”
§ Persistent Gut Microbiota Immaturity in Malnourished Bangladeshi Children > Extended Data
plaincorrelationaln = 33- Asserted: passes — The authors put it forward as true.
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In the paper
“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”
§ Persistent Gut Microbiota Immaturity in Malnourished Bangladeshi Children > The effects of SAM on microbiota maturity
plaindirect- Asserted: passes — The authors put it forward as true.
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In the paper
“Diarrhea | -0.44 | 0.15 | 0.0028”
§ Persistent Gut Microbiota Immaturity in Malnourished Bangladeshi Children > Extended Data
plaindirect- Asserted: passes — The authors put it forward as true.
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The quote only partly states this claim.
A result the paper reports from its own data — it cites no other source for it, so there is none to check. The quote shows it is in the paper.
In the paper
“The reduced bacterial diversity associated with SAM persisted after Khichuri-Halwa and only transiently improved with RUTF”
§ Persistent Gut Microbiota Immaturity in Malnourished Bangladeshi Children > The effects of SAM on microbiota maturity
plaindirect- Asserted: passes — The authors put it forward as true.
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In the paper
“Month following Diarrhea | -0.37 | 0.16 | 0.0247”
§ Persistent Gut Microbiota Immaturity in Malnourished Bangladeshi Children > Extended Data
plaindirect- Asserted: passes — The authors put it forward as true.
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In the paper
“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”
§ Persistent Gut Microbiota Immaturity in Malnourished Bangladeshi Children > The effects of SAM on microbiota maturity
plaincorrelationaln = 10- Asserted: passes — The authors put it forward as true.
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In the paper
“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”
§ Persistent Gut Microbiota Immaturity in Malnourished Bangladeshi Children > The effects of SAM on microbiota maturity
plaincorrelational- Asserted: passes — The authors put it forward as true.
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A result the paper reports from its own data — it cites no other source for it, so there is none to check. The quote shows it is in the paper.
In the paper
“Three of these 97%ID OTUs are members of the top 24 age-discriminatory taxa (blue) and belong to the genus Bifidobacterium.”
§ Persistent Gut Microbiota Immaturity in Malnourished Bangladeshi Children > Extended Data
plainn = 3- Asserted: passes — The authors put it forward as true.
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In the paper
“opposing changes in the relative abundance of Streptococcaceae and Enterobacteriaceae were readily apparent”
§ Persistent Gut Microbiota Immaturity in Malnourished Bangladeshi Children > The effects of SAM on microbiota maturity
plaincorrelationaln = 9- Asserted: passes — The authors put it forward as true.
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In the paper
“Antibiotics | RUTF | -0.37 | 0.81 | 0.65”
§ Persistent Gut Microbiota Immaturity in Malnourished Bangladeshi Children > Extended Data
plain- Asserted: passes — The authors put it forward as true.
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In the paper
“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”
§ Persistent Gut Microbiota Immaturity in Malnourished Bangladeshi Children > Abstract
plaincorrelational- Asserted: passes — The authors put it forward as true.
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In the paper
“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)”
§ Persistent Gut Microbiota Immaturity in Malnourished Bangladeshi Children > The effects of SAM on microbiota maturity
plaincorrelational- Asserted: passes — The authors put it forward as true.
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In the paper
“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).”
§ Persistent Gut Microbiota Immaturity in Malnourished Bangladeshi Children > The effects of SAM on microbiota maturity
plaincorrelationaln = 23- Asserted: passes — The authors put it forward as true.
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In the paper
“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”
§ Persistent Gut Microbiota Immaturity in Malnourished Bangladeshi Children > The effects of SAM on microbiota maturity
plainn = 9- Asserted: passes — The authors put it forward as true.
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In the paper
“At enrollment, WHZ scores averaged -4.2±0.7 (mean±SD)”
§ Persistent Gut Microbiota Immaturity in Malnourished Bangladeshi Children > The effects of SAM on microbiota maturity
plainn = 4- Asserted: passes — The authors put it forward as true.
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In the paper
“Formula | +0.22 | 0.11 | 0.04”
§ Persistent Gut Microbiota Immaturity in Malnourished Bangladeshi Children > Extended Data
plaindirect- Asserted: passes — The authors put it forward as true.
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In the paper
“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).”
§ Persistent Gut Microbiota Immaturity in Malnourished Bangladeshi Children > Methods > Twins/Triplets birth cohort
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In the paper
“Enrollment | RUTF | -5.62 | 0.78 | <0.001”
§ Persistent Gut Microbiota Immaturity in Malnourished Bangladeshi Children > Extended Data
plain- Asserted: passes — The authors put it forward as true.
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In the paper
“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).”
§ Persistent Gut Microbiota Immaturity in Malnourished Bangladeshi Children > Extended Data
plaincorrelational- Asserted: passes — The authors put it forward as true.
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In the paper
“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.”
§ Persistent Gut Microbiota Immaturity in Malnourished Bangladeshi Children > Extended Data
plainn = 10- Asserted: passes — The authors put it forward as true.
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None of the sources cited for this claim have been checked yet.
In the paper
“There is similar lack of clarity about the long-term efficacy of nutritional interventions for MAM7,8.”
§ Persistent Gut Microbiota Immaturity in Malnourished Bangladeshi Children > Abstract
What the sources say
- Not checked yetcites [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 yetcites [8] Prentice, A. M. et al. Critical windows for nutritional interventions against stunting. Am. J. Clin. Nutr. 97, 911–918 (2013) source
plain- Asserted: passes — The authors put it forward as true.
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Probably not a substantial claim. The paper’s conclusions may not depend on it.
None of the sources cited for this claim have been checked yet.
In the paper
“Therapeutic food interventions have reduced mortality in children with severe acute malnutrition (SAM) but incomplete restoration of healthy growth remains a major problem1,2.”
§ Persistent Gut Microbiota Immaturity in Malnourished Bangladeshi Children > Abstract
What the sources say
- Not checked yetcites [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 yetcites [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
plaindirect- Asserted: passes — The authors put it forward as true.
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In the paper
“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”
§ Persistent Gut Microbiota Immaturity in Malnourished Bangladeshi Children > Abstract
What the sources say
- Not checked yetcites [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 yetcites [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
hedged- Asserted: passes — The authors put it forward as true.
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- Based: passes — The paper gives a reason why it holds.
Probably not a substantial claim. The paper’s conclusions may not depend on it.
A conclusion the paper draws from its own results — it cites no other source for it, so there is none to check. The quote shows it is in the paper.
In the paper
“Microbiota maturity indices provide a microbial measure of human postnatal development, a way of classifying malnourished states, and a parameter for judging therapeutic efficacy.”
§ Persistent Gut Microbiota Immaturity in Malnourished Bangladeshi Children > Abstract
plaincorrelational- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: passes — The paper’s conclusions depend on it.
- Based: passes — The paper gives a reason why it holds.
It may state two separate claims as one.
In the paper
“A standardized treatment protocol for SAM and its complications has been developed in Bangladesh1.”
§ Persistent Gut Microbiota Immaturity in Malnourished Bangladeshi Children > Abstract
What the sources say
- Not checked yetcites [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
plain- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: fails — The paper’s conclusions may not depend on it.
- Based: passes — The paper gives a reason why it holds.
Probably not a substantial claim. The paper’s conclusions may not depend on it.
None of the sources cited for this claim have been checked yet.
In the paper
“Food is a major factor that shapes the proportional representation of organisms present in the gut microbial community (microbiota), and its gene content (microbiome).”
§ Persistent Gut Microbiota Immaturity in Malnourished Bangladeshi Children > Abstract
What the sources say
- Not checked yetcites [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 yetcites [10] Wu, G. D. et al. Linking long-term dietary patterns with gut microbial enterotypes. Science 334, 105–108 (2011) source
- Not checked yetcites [11] Yatsunenko, T. et al. Human gut microbiome viewed across age and geography. Nature 486, 222–227 (2012) source
- Not checked yetcites [12] Smith, M. I. et al. Gut microbiomes of Malawian twin pairs discordant for kwashiorkor. Science 339, 548–554 (2013) source
- Not checked yetcites [13] David, L. A. et al. Diet rapidly and reproducibly alters the human gut microbiome. Nature 505, 559–563 (2014) source
- Not checked yetcites [14] Tang, W. H. W. et al. Intestinal microbial metabolism of phosphatidylcholine and cardiovascular risk. N. Engl. J. Med. 368, 1575–1584 (2013) source
plaindirect- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: passes — The paper’s conclusions depend on it.
- Based: passes — The paper gives a reason why it holds.
It may state two separate claims as one.
None of the sources cited for this claim have been checked yet.
In the paper
“The microbiota/microbiome in turn plays an important role in extracting and metabolizing dietary ingredients9-14.”
§ Persistent Gut Microbiota Immaturity in Malnourished Bangladeshi Children > Abstract
What the sources say
- Not checked yetcites [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 yetcites [10] Wu, G. D. et al. Linking long-term dietary patterns with gut microbial enterotypes. Science 334, 105–108 (2011) source
- Not checked yetcites [11] Yatsunenko, T. et al. Human gut microbiome viewed across age and geography. Nature 486, 222–227 (2012) source
- Not checked yetcites [12] Smith, M. I. et al. Gut microbiomes of Malawian twin pairs discordant for kwashiorkor. Science 339, 548–554 (2013) source
- Not checked yetcites [13] David, L. A. et al. Diet rapidly and reproducibly alters the human gut microbiome. Nature 505, 559–563 (2014) source
- Not checked yetcites [14] Tang, W. H. W. et al. Intestinal microbial metabolism of phosphatidylcholine and cardiovascular risk. N. Engl. J. Med. 368, 1575–1584 (2013) source
plaindirect- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: fails — The paper’s conclusions may not depend on it.
- Based: passes — The paper gives a reason why it holds.
Probably not a substantial claim. The paper’s conclusions may not depend on it.
In the paper
“SAM and MAM typically develop between three and 24 months of life4.”
§ Persistent Gut Microbiota Immaturity in Malnourished Bangladeshi Children > Abstract
What the sources say
- Not checked yetcites [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
plain- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: fails — The paper’s conclusions may not depend on it.
- Based: passes — The paper gives a reason why it holds.
Probably not a substantial claim. The paper’s conclusions may not depend on it.
What the paper did — it cites no source for this, so there is none to check. The quote shows it is in the paper.
In the paper
“‘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.”
§ Persistent Gut Microbiota Immaturity in Malnourished Bangladeshi Children > Methods > Characterizing the bacterial component of the gut microbiota by V4-16S rRNA sequencing
plain- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: fails — The paper’s conclusions may not depend on it.
- Based: passes — The paper gives a reason why it holds.
Probably not a substantial claim. The paper’s conclusions may not depend on it.
What the paper did — it cites no source for this, so there is none to check. The quote shows it is in the paper.
In the paper
“clinical trial NCT01331044”
§ Persistent Gut Microbiota Immaturity in Malnourished Bangladeshi Children > Methods > Severe Acute Malnutrition (SAM) study
plain- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: fails — The paper’s conclusions may not depend on it.
- Based: passes — The paper gives a reason why it holds.
Probably not a substantial claim. The paper’s conclusions may not depend on it.
What the paper did — it cites no source for this, so there is none to check. The quote shows it is in the paper.
In the paper
“This survey, approved by the Washington University and icddr,b IRBs”
§ Persistent Gut Microbiota Immaturity in Malnourished Bangladeshi Children > Methods > Anthropologic study
plain- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: fails — The paper’s conclusions may not depend on it.
- Based: passes — The paper gives a reason why it holds.
Probably not a substantial claim. The paper’s conclusions may not depend on it. It may state two separate claims as one.
In the paper
“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.”
§ Persistent Gut Microbiota Immaturity in Malnourished Bangladeshi Children > The effects of SAM on microbiota maturity
What the sources say
- Not checked yetcites [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
hedgedcorrelational- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: fails — The paper’s conclusions may not depend on it.
- Based: passes — The paper gives a reason why it holds.
Probably not a substantial claim. The paper’s conclusions may not depend on it. It may state two separate claims as one.
What the paper did — it cites no source for this, so there is none to check. The quote shows it is in the paper.
In the paper
“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”
§ Persistent Gut Microbiota Immaturity in Malnourished Bangladeshi Children > The effects of SAM on microbiota maturity
hedged- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: fails — The paper’s conclusions may not depend on it.
- Based: passes — The paper gives a reason why it holds.
Probably not a substantial claim. The paper’s conclusions may not depend on it.
None of the sources cited for this claim have been checked yet.
In the paper
“Data from the mock communities were used for diversity and precisionsensitivity analyses employing methods described previously15,23.”
§ Persistent Gut Microbiota Immaturity in Malnourished Bangladeshi Children > Methods > Characterizing the bacterial component of the gut microbiota by V4-16S rRNA sequencing
What the sources say
plain- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: fails — The paper’s conclusions may not depend on it.
- Based: passes — The paper gives a reason why it holds.
Probably not a substantial claim. The paper’s conclusions may not depend on it.
What the paper did — it cites no source for this, so there is none to check. The quote shows it is in the paper.
In the paper
“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).”
§ Persistent Gut Microbiota Immaturity in Malnourished Bangladeshi Children > Methods > Twins/Triplets birth cohort
plainn = 11- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: fails — The paper’s conclusions may not depend on it.
- Based: passes — The paper gives a reason why it holds.
Probably not a substantial claim. The paper’s conclusions may not depend on it.
What the paper did — it cites no source for this, so there is none to check. The quote shows it is in the paper.
In the paper
“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.”
§ Persistent Gut Microbiota Immaturity in Malnourished Bangladeshi Children > Methods > Defining maturation of the gut microbiota in healthy children using Random Forests
plainn = 272- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: passes — The paper’s conclusions depend on it.
- Based: passes — The paper gives a reason why it holds.
Probably not a substantial claim. It may state two separate claims as one.
What the paper did — it cites no source for this, so there is none to check. The quote shows it is in the paper.
In the paper
“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.”
§ Persistent Gut Microbiota Immaturity in Malnourished Bangladeshi Children > The effects of SAM on microbiota maturity
plainn = 4- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: fails — The paper’s conclusions may not depend on it.
- Based: passes — The paper gives a reason why it holds.
Probably not a substantial claim. The paper’s conclusions may not depend on it.
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.”
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?
In the citing paper
“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]
In the citing paper
“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.
Rated major: it would touch a result — a value a result rests on, reported and recomputed p-values on opposite sides of the significance level, two passages that conflict with no sign which is right, or a cited work retracted before this paper was published.
In the paper
§ Persistent Gut Microbiota Immaturity in Malnourished Bangladeshi Children > The effects of SAM on microbiota maturity
“Within one month of follow-up, both groups had improved significantly.”
§ Persistent Gut Microbiota Immaturity in Malnourished Bangladeshi Children > Extended Data
“| < 1 month | Khichuri-Halwa | 0.92 | 0.74 | 0.76 |”
Rated minor: it would not touch a result — a value no result rests on, a p-value that stays on the same side of the significance level, or a conflict that is clerical, resolved elsewhere in the paper, or outside its own findings.
In the paper
§ Persistent Gut Microbiota Immaturity in Malnourished Bangladeshi Children > Extended Data
“WHZ scores are significantly inversely correlated with relative microbiota maturity (panel a) and MAZ scores (panel b)”
§ Persistent Gut Microbiota Immaturity in Malnourished Bangladeshi Children > Extended Data
“Spearman rho = 0.62 and 0.63, respectively”
Citations
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“The prediction model was selected by the random forest method and cross-validation was used to select biomarkers for predicting disease versus health [31].”
Metadata
- 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
- Published
- 2014-06
- Volume
- 510
- Issue
- 7505
- Pages
- 417-421
- ISSN
- 0028-0836 (ISSN-L)
- 1476-4687
- 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
- green
- www.ncbi.nlm.nih.gov
- 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
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