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Microbial-Derived Metabolites Reflect an Altered Intestinal Microbiota during Catch-Up Growth in Undernourished Neonatal Mice.
J Nutr 2016; 146(5):940-8JN

Abstract

BACKGROUND

Protein-energy undernutrition during early development confers a lifelong increased risk of obesity-related metabolic disease. Mechanisms by which metabolic abnormalities persist despite catch-up growth are poorly understood.

OBJECTIVE

We sought to determine whether abnormal metabolomic and intestinal microbiota profiles from undernourished neonatal mice remain altered during catch-up growth.

METHODS

Male and female CD1 mouse pups were undernourished by timed separation from lactating dams for 4 h at 5 d of age, 8 h at 6 d of age, and 12 h/d from 7 to 15 d of age, then resumed ad libitum nursing, whereas controls fed uninterrupted. Both groups were weaned simultaneously to a standard unpurified diet. At 3 time points (0, 1, and 3 wk after ending feed deprivation), metabolites in urine, plasma, and stool were identified with the use of mass spectrometry, and fecal microbes were identified with the use of 16S metagenomic sequencing.

RESULTS

Undernourished mice completely recovered deficits of 36% weight and 9% length by 3 wk of refeeding, at which time they had 1.4-fold higher plasma phenyllactate and 2.0-fold higher urinary p-cresol sulfate concentrations than did controls. Plasma serotonin concentrations in undernourished mice were 25% lower at 0 wk but 1.5-fold higher than in controls at 3 wk. Whereas most urine and plasma metabolites normalized with refeeding, 117 fecal metabolites remained altered at 3 wk, including multiple N-linked glycans. Microbiota profiles from undernourished mice also remained distinct, with lower mean proportions of Bacteroidetes (67% compared with 83%) and higher proportions of Firmicutes (26% compared with 16%). Abundances of the mucolytic organisms Akkermansia muciniphila and Mucispirillum schaedleri were altered at 0 and 1 wk. Whereas microbiota from undernourished mice at 0 wk contained 11% less community diversity (P = 0.015), refed mice at 3 wk harbored 1.2-fold greater diversity (P = 0.0006) than did controls.

CONCLUSION

Microbial-derived metabolites and intestinal microbiota remain altered during catch-up growth in undernourished neonatal mice.

Authors+Show Affiliations

Section of Gastroenterology, Hepatology and Nutrition, Department of Pediatrics, Baylor College of Medicine and Texas Children's Hospital, Houston, TX; and geoffrey.preidis@bcm.edu.Department of Molecular Virology and Microbiology and Alkek Center for Metagenomics and Microbiome Research, Baylor College of Medicine, Houston, TX.Department of Molecular Virology and Microbiology and Alkek Center for Metagenomics and Microbiome Research, Baylor College of Medicine, Houston, TX.Section of Gastroenterology, Hepatology and Nutrition, Department of Pediatrics, Baylor College of Medicine and Texas Children's Hospital, Houston, TX; and.Department of Molecular Virology and Microbiology and.Department of Molecular Virology and Microbiology and Alkek Center for Metagenomics and Microbiome Research, Baylor College of Medicine, Houston, TX.

Pub Type(s)

Journal Article

Language

eng

PubMed ID

27052538

Citation

Preidis, Geoffrey A., et al. "Microbial-Derived Metabolites Reflect an Altered Intestinal Microbiota During Catch-Up Growth in Undernourished Neonatal Mice." The Journal of Nutrition, vol. 146, no. 5, 2016, pp. 940-8.
Preidis GA, Ajami NJ, Wong MC, et al. Microbial-Derived Metabolites Reflect an Altered Intestinal Microbiota during Catch-Up Growth in Undernourished Neonatal Mice. J Nutr. 2016;146(5):940-8.
Preidis, G. A., Ajami, N. J., Wong, M. C., Bessard, B. C., Conner, M. E., & Petrosino, J. F. (2016). Microbial-Derived Metabolites Reflect an Altered Intestinal Microbiota during Catch-Up Growth in Undernourished Neonatal Mice. The Journal of Nutrition, 146(5), pp. 940-8. doi:10.3945/jn.115.229179.
Preidis GA, et al. Microbial-Derived Metabolites Reflect an Altered Intestinal Microbiota During Catch-Up Growth in Undernourished Neonatal Mice. J Nutr. 2016;146(5):940-8. PubMed PMID: 27052538.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - Microbial-Derived Metabolites Reflect an Altered Intestinal Microbiota during Catch-Up Growth in Undernourished Neonatal Mice. AU - Preidis,Geoffrey A, AU - Ajami,Nadim J, AU - Wong,Matthew C, AU - Bessard,Brooke C, AU - Conner,Margaret E, AU - Petrosino,Joseph F, Y1 - 2016/04/06/ PY - 2015/12/28/received PY - 2016/02/16/accepted PY - 2016/4/8/entrez PY - 2016/4/8/pubmed PY - 2017/6/10/medline KW - N-linked glycans KW - metabolomics KW - metagenomics KW - mucolytic bacteria KW - neonatal mice KW - one-carbon metabolism KW - p-cresol sulfate KW - phenyllactate KW - protein-energy undernutrition KW - serotonin SP - 940 EP - 8 JF - The Journal of nutrition JO - J. Nutr. VL - 146 IS - 5 N2 - BACKGROUND: Protein-energy undernutrition during early development confers a lifelong increased risk of obesity-related metabolic disease. Mechanisms by which metabolic abnormalities persist despite catch-up growth are poorly understood. OBJECTIVE: We sought to determine whether abnormal metabolomic and intestinal microbiota profiles from undernourished neonatal mice remain altered during catch-up growth. METHODS: Male and female CD1 mouse pups were undernourished by timed separation from lactating dams for 4 h at 5 d of age, 8 h at 6 d of age, and 12 h/d from 7 to 15 d of age, then resumed ad libitum nursing, whereas controls fed uninterrupted. Both groups were weaned simultaneously to a standard unpurified diet. At 3 time points (0, 1, and 3 wk after ending feed deprivation), metabolites in urine, plasma, and stool were identified with the use of mass spectrometry, and fecal microbes were identified with the use of 16S metagenomic sequencing. RESULTS: Undernourished mice completely recovered deficits of 36% weight and 9% length by 3 wk of refeeding, at which time they had 1.4-fold higher plasma phenyllactate and 2.0-fold higher urinary p-cresol sulfate concentrations than did controls. Plasma serotonin concentrations in undernourished mice were 25% lower at 0 wk but 1.5-fold higher than in controls at 3 wk. Whereas most urine and plasma metabolites normalized with refeeding, 117 fecal metabolites remained altered at 3 wk, including multiple N-linked glycans. Microbiota profiles from undernourished mice also remained distinct, with lower mean proportions of Bacteroidetes (67% compared with 83%) and higher proportions of Firmicutes (26% compared with 16%). Abundances of the mucolytic organisms Akkermansia muciniphila and Mucispirillum schaedleri were altered at 0 and 1 wk. Whereas microbiota from undernourished mice at 0 wk contained 11% less community diversity (P = 0.015), refed mice at 3 wk harbored 1.2-fold greater diversity (P = 0.0006) than did controls. CONCLUSION: Microbial-derived metabolites and intestinal microbiota remain altered during catch-up growth in undernourished neonatal mice. SN - 1541-6100 UR - https://www.unboundmedicine.com/medline/citation/27052538/Microbial_Derived_Metabolites_Reflect_an_Altered_Intestinal_Microbiota_during_Catch_Up_Growth_in_Undernourished_Neonatal_Mice_ L2 - https://academic.oup.com/jn/article-lookup/doi/10.3945/jn.115.229179 DB - PRIME DP - Unbound Medicine ER -