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Dietary Modulation of Gut Microbiota Contributes to Alleviation of Both Genetic and Simple Obesity in Children.

Zhang C, Yin A, Li H, Wang R, Wu G, Shen J, Zhang M, Wang L, Hou Y, Ouyang H, Zhang Y, Zheng Y, Wang J, Lv X, Wang Y, Zhang F, Zeng B, Li W, Yan F, Zhao Y, Pang X, Zhang X, Fu H, Chen F, Zhao N, Hamaker BR, Bridgewater LC, Weinkove D, Clement K, Dore J, Holmes E, Xiao H, Zhao G, Yang S, Bork P, Nicholson JK, Wei H, Tang H, Zhang X, Zhao L - EBioMedicine (2015)

Bottom Line: NMR-based metabolomic profiling of urine showed diet-induced overall changes of host metabotypes and identified significantly reduced trimethylamine N-oxide and indoxyl sulfate, host-bacteria co-metabolites known to induce metabolic deteriorations.Specific bacterial genomes that were correlated with urine levels of these detrimental co-metabolites were found to encode enzyme genes for production of their precursors by fermentation of choline or tryptophan in the gut.A diet rich in non-digestible but fermentable carbohydrates significantly promoted beneficial groups of bacteria and reduced toxin-producers, which contributes to the alleviation of metabolic deteriorations in obesity regardless of the primary driving forces.

View Article: PubMed Central - PubMed

Affiliation: State Key Laboratory of Microbial Metabolism and Ministry of Education Key Laboratory of Systems Biomedicine, School of Life Sciences and Biotechnology, Shanghai Jiao Tong University, Shanghai 200240, China.

ABSTRACT

Unlabelled: Gut microbiota has been implicated as a pivotal contributing factor in diet-related obesity; however, its role in development of disease phenotypes in human genetic obesity such as Prader-Willi syndrome (PWS) remains elusive. In this hospitalized intervention trial with PWS (n = 17) and simple obesity (n = 21) children, a diet rich in non-digestible carbohydrates induced significant weight loss and concomitant structural changes of the gut microbiota together with reduction of serum antigen load and alleviation of inflammation. Co-abundance network analysis of 161 prevalent bacterial draft genomes assembled directly from metagenomic datasets showed relative increase of functional genome groups for acetate production from carbohydrates fermentation. NMR-based metabolomic profiling of urine showed diet-induced overall changes of host metabotypes and identified significantly reduced trimethylamine N-oxide and indoxyl sulfate, host-bacteria co-metabolites known to induce metabolic deteriorations. Specific bacterial genomes that were correlated with urine levels of these detrimental co-metabolites were found to encode enzyme genes for production of their precursors by fermentation of choline or tryptophan in the gut. When transplanted into germ-free mice, the pre-intervention gut microbiota induced higher inflammation and larger adipocytes compared with the post-intervention microbiota from the same volunteer. Our multi-omics-based systems analysis indicates a significant etiological contribution of dysbiotic gut microbiota to both genetic and simple obesity in children, implicating a potentially effective target for alleviation.

Research in context: Poorly managed diet and genetic mutations are the two primary driving forces behind the devastating epidemic of obesity-related diseases. Lack of understanding of the molecular chain of causation between the driving forces and the disease endpoints retards progress in prevention and treatment of the diseases. We found that children genetically obese with Prader-Willi syndrome shared a similar dysbiosis in their gut microbiota with those having diet-related obesity. A diet rich in non-digestible but fermentable carbohydrates significantly promoted beneficial groups of bacteria and reduced toxin-producers, which contributes to the alleviation of metabolic deteriorations in obesity regardless of the primary driving forces.

No MeSH data available.


Related in: MedlinePlus

Functional shifts of the gut microbiome during the dietary intervention. (a) The PCA score plot of the KO Groups recognized with HUMAnN showing a significant shift of the KO profiles after the intervention (log-transformed). (b) Clustering of KO profiles based on distances between different groups calculated with MANOVA test of the first five PCs of PCA of KO. (c) Key pathways of gut microbiota responding to dietary intervention. The left histogram shows the LDA scores computed for features (on the pathway level) differentially abundant between all samples before and after the intervention. The heat map shows the abundance of the key pathways. The stacked bar chart shows relative contribution of GIGs to each pathway. For PWS, n = 17 at Day 0, 30, 60, and 90; For SO, n = 21 at Day 0 and n = 20 at Day 30. In (c) day 0 and day 30 data of PWS and SO combined together for this analysis.
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f0020: Functional shifts of the gut microbiome during the dietary intervention. (a) The PCA score plot of the KO Groups recognized with HUMAnN showing a significant shift of the KO profiles after the intervention (log-transformed). (b) Clustering of KO profiles based on distances between different groups calculated with MANOVA test of the first five PCs of PCA of KO. (c) Key pathways of gut microbiota responding to dietary intervention. The left histogram shows the LDA scores computed for features (on the pathway level) differentially abundant between all samples before and after the intervention. The heat map shows the abundance of the key pathways. The stacked bar chart shows relative contribution of GIGs to each pathway. For PWS, n = 17 at Day 0, 30, 60, and 90; For SO, n = 21 at Day 0 and n = 20 at Day 30. In (c) day 0 and day 30 data of PWS and SO combined together for this analysis.

Mentions: To see how the altered community structure of the gut microbiota affected its metabolic potential, we profiled the metagenomic data using HUMAnN to identify and quantify genes within biochemical pathways (Abubucker et al., 2012). In total, 5234 KEGG orthology groups (KOs) were recognized and quantified. The PCA score plot of all the KOs showed a significant shift after the intervention (MANOVA test, P = 2.00e − 7, Fig. 4a and b), indicating a modulation of the metabolic capacity of the gut microbiota concomitant with its diet-induced structural changes. There was no significant difference between the PWS and SO cohorts either before or after the intervention (MANOVA test P = 0.712 and P = 0.291, Fig. 4b). Thus, gut microbiota between PWS and SO children shared similar structural and functional features both before and after the intervention.


Dietary Modulation of Gut Microbiota Contributes to Alleviation of Both Genetic and Simple Obesity in Children.

Zhang C, Yin A, Li H, Wang R, Wu G, Shen J, Zhang M, Wang L, Hou Y, Ouyang H, Zhang Y, Zheng Y, Wang J, Lv X, Wang Y, Zhang F, Zeng B, Li W, Yan F, Zhao Y, Pang X, Zhang X, Fu H, Chen F, Zhao N, Hamaker BR, Bridgewater LC, Weinkove D, Clement K, Dore J, Holmes E, Xiao H, Zhao G, Yang S, Bork P, Nicholson JK, Wei H, Tang H, Zhang X, Zhao L - EBioMedicine (2015)

Functional shifts of the gut microbiome during the dietary intervention. (a) The PCA score plot of the KO Groups recognized with HUMAnN showing a significant shift of the KO profiles after the intervention (log-transformed). (b) Clustering of KO profiles based on distances between different groups calculated with MANOVA test of the first five PCs of PCA of KO. (c) Key pathways of gut microbiota responding to dietary intervention. The left histogram shows the LDA scores computed for features (on the pathway level) differentially abundant between all samples before and after the intervention. The heat map shows the abundance of the key pathways. The stacked bar chart shows relative contribution of GIGs to each pathway. For PWS, n = 17 at Day 0, 30, 60, and 90; For SO, n = 21 at Day 0 and n = 20 at Day 30. In (c) day 0 and day 30 data of PWS and SO combined together for this analysis.
© Copyright Policy - CC BY-NC-ND
Related In: Results  -  Collection

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Show All Figures
getmorefigures.php?uid=PMC4563136&req=5

f0020: Functional shifts of the gut microbiome during the dietary intervention. (a) The PCA score plot of the KO Groups recognized with HUMAnN showing a significant shift of the KO profiles after the intervention (log-transformed). (b) Clustering of KO profiles based on distances between different groups calculated with MANOVA test of the first five PCs of PCA of KO. (c) Key pathways of gut microbiota responding to dietary intervention. The left histogram shows the LDA scores computed for features (on the pathway level) differentially abundant between all samples before and after the intervention. The heat map shows the abundance of the key pathways. The stacked bar chart shows relative contribution of GIGs to each pathway. For PWS, n = 17 at Day 0, 30, 60, and 90; For SO, n = 21 at Day 0 and n = 20 at Day 30. In (c) day 0 and day 30 data of PWS and SO combined together for this analysis.
Mentions: To see how the altered community structure of the gut microbiota affected its metabolic potential, we profiled the metagenomic data using HUMAnN to identify and quantify genes within biochemical pathways (Abubucker et al., 2012). In total, 5234 KEGG orthology groups (KOs) were recognized and quantified. The PCA score plot of all the KOs showed a significant shift after the intervention (MANOVA test, P = 2.00e − 7, Fig. 4a and b), indicating a modulation of the metabolic capacity of the gut microbiota concomitant with its diet-induced structural changes. There was no significant difference between the PWS and SO cohorts either before or after the intervention (MANOVA test P = 0.712 and P = 0.291, Fig. 4b). Thus, gut microbiota between PWS and SO children shared similar structural and functional features both before and after the intervention.

Bottom Line: NMR-based metabolomic profiling of urine showed diet-induced overall changes of host metabotypes and identified significantly reduced trimethylamine N-oxide and indoxyl sulfate, host-bacteria co-metabolites known to induce metabolic deteriorations.Specific bacterial genomes that were correlated with urine levels of these detrimental co-metabolites were found to encode enzyme genes for production of their precursors by fermentation of choline or tryptophan in the gut.A diet rich in non-digestible but fermentable carbohydrates significantly promoted beneficial groups of bacteria and reduced toxin-producers, which contributes to the alleviation of metabolic deteriorations in obesity regardless of the primary driving forces.

View Article: PubMed Central - PubMed

Affiliation: State Key Laboratory of Microbial Metabolism and Ministry of Education Key Laboratory of Systems Biomedicine, School of Life Sciences and Biotechnology, Shanghai Jiao Tong University, Shanghai 200240, China.

ABSTRACT

Unlabelled: Gut microbiota has been implicated as a pivotal contributing factor in diet-related obesity; however, its role in development of disease phenotypes in human genetic obesity such as Prader-Willi syndrome (PWS) remains elusive. In this hospitalized intervention trial with PWS (n = 17) and simple obesity (n = 21) children, a diet rich in non-digestible carbohydrates induced significant weight loss and concomitant structural changes of the gut microbiota together with reduction of serum antigen load and alleviation of inflammation. Co-abundance network analysis of 161 prevalent bacterial draft genomes assembled directly from metagenomic datasets showed relative increase of functional genome groups for acetate production from carbohydrates fermentation. NMR-based metabolomic profiling of urine showed diet-induced overall changes of host metabotypes and identified significantly reduced trimethylamine N-oxide and indoxyl sulfate, host-bacteria co-metabolites known to induce metabolic deteriorations. Specific bacterial genomes that were correlated with urine levels of these detrimental co-metabolites were found to encode enzyme genes for production of their precursors by fermentation of choline or tryptophan in the gut. When transplanted into germ-free mice, the pre-intervention gut microbiota induced higher inflammation and larger adipocytes compared with the post-intervention microbiota from the same volunteer. Our multi-omics-based systems analysis indicates a significant etiological contribution of dysbiotic gut microbiota to both genetic and simple obesity in children, implicating a potentially effective target for alleviation.

Research in context: Poorly managed diet and genetic mutations are the two primary driving forces behind the devastating epidemic of obesity-related diseases. Lack of understanding of the molecular chain of causation between the driving forces and the disease endpoints retards progress in prevention and treatment of the diseases. We found that children genetically obese with Prader-Willi syndrome shared a similar dysbiosis in their gut microbiota with those having diet-related obesity. A diet rich in non-digestible but fermentable carbohydrates significantly promoted beneficial groups of bacteria and reduced toxin-producers, which contributes to the alleviation of metabolic deteriorations in obesity regardless of the primary driving forces.

No MeSH data available.


Related in: MedlinePlus