The fecal metabolome as a functional readout of the gut microbiome

Zierer, Jonas; Jackson, Matthew A.; Kastenmüller, Gabi; Mangino, Massimo; Long, Tao; Telenti, Amalio; Mohney, Robert P.; Small, Kerrin S.; Bell, Jordana T.; Steves, Claire J.; Valdes, Ana M.; Spector, Tim D.; Menni, Cristina

doi:10.1038/s41588-018-0135-7

Cited by 549 publications

(503 citation statements)

References 54 publications

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“…Metabolomics and the gut microbiome are strongly related, and a metabolomics approach sheds light on the type of microbes present in the gut and their metabolic interactions . In this study, amino acid metabolism, the most common metabolic pathway in the gut, was inversely correlated with the abundance of the phylum Firmicutes which is the dominant component of the fecal microbiome.…”

Section: Discussionmentioning

confidence: 77%

“…A metabolomics approach has been applied to studies on the gut microbiome for detailed information on the metabolic pathways leading to the development of diseases. The fecal metabolome provides a complementary functional approach to the gut microbial metabolism and its interaction with the host, offering the opportunity to characterize diseases effectively . Clinically, house dust mite sensitization with elevated serum immunoglobulin E (IgE) levels is a significant factor in relation to both allergic rhinitis and asthma .…”

Section: Introductionmentioning

confidence: 99%

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Gut microbial‐derived butyrate is inversely associated with IgE responses to allergens in childhood asthma

Chiu

Cheng

Chiang

et al. 2019

Pediatric Allergy Immunology

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Background A comprehensive metabolomics‐based approach to address the impact of specific gut microbiota on allergen sensitization for childhood rhinitis and asthma is still lacking. Methods Eighty‐five children with rhinitis (n = 27) and with asthma (n = 34) and healthy controls (n = 24) were enrolled. Fecal metabolomic analysis with 1H‐nuclear magnetic resonance (NMR) spectroscopy and microbiome composition analysis by bacterial 16S rRNA sequencing were performed. An integrative analysis of their associations with allergen‐specific IgE levels for allergic rhinitis and asthma was also assessed. Results Amino acid, β‐alanine, and butanoate were the predominant metabolic pathways in the gut. Among them, amino acid metabolism was negatively correlated with the phylum Firmicutes, which was significantly reduced in children with rhinitis and asthma. Levels of histidine and butyrate metabolites were significantly reduced in children with rhinitis (P = 0.029) and asthma (P = 0.009), respectively. In children with asthma, a reduction in butyrate‐producing bacteria, including Faecalibacterium and Roseburia spp., and an increase in Clostridium spp. were negatively correlated with fecal amino acids and butyrate, respectively (P < 0.01). Increased Escherichia spp. accompanied by increased β‐alanine and 4‐hydroxybutyrate appeared to reduce butyrate production. Low fecal butyrate was significantly associated with increased total serum and mite allergen–specific IgE levels in children with asthma (P < 0.05). Conclusion A reduced fecal butyrate is associated with increased mite‐specific IgE levels and the risk of asthma in early childhood. Fecal β‐alanine could be a specific biomarker connecting the metabolic dysbiosis of gut microbiota, Clostridium and Escherichia spp., in childhood asthma.

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Section: Discussionmentioning

confidence: 77%

Section: Introductionmentioning

confidence: 99%

Gut microbial‐derived butyrate is inversely associated with IgE responses to allergens in childhood asthma

Chiu

Cheng

Chiang

et al. 2019

Pediatric Allergy Immunology

View full text Add to dashboard Cite

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“…7 A large portion of the variance in fecal metabolites can be explained by the composition of the fecal microbiome. 7, 8 Dysbiosis is associated with the pathogenesis of several gastrointestinal diseases (inflammatory bowel disease, irritable bowel syndrome) 9 , as well as other diseases such as obesity, the metabolic syndrome, diabetes 10–12 and pancreatic diseases including pancreatic cancer. 1314 …”

Section: Introductionmentioning

confidence: 99%

The Gut Microbiome in Pancreatic Disease

Akshintala¹,

Talukdar

Singh³

et al. 2019

Clinical Gastroenterology and Hepatology

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The gut microbiome is increasingly recognized for its role in human health and disease. Initial evidence indicates that gut microbial dysbiosis is associated with several pancreatic diseases. Although it is not known if these associations are causative, gut dysbiosis is hypothesized to mediate chronic pro-inflammatory changes in the pancreas. Further mechanistic and epidemiological studies of the microbiome are needed. Ultimately, targeted modulation of the microbiota could have therapeutic value.

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“…The faecal metabolome provides a functional readout of gut microbial activity and has been found to reflect, on average, 67.7% of the gut microbial composition (Zierer et al . ). The close relationship between the faecal metabolome and faecal microbiome is a result of the inter‐individual nature of the gut microbiome, differences in gastrointestinal transit and personalised diets.…”

Section: Diet Shapes the Gut Metabolomementioning

confidence: 97%

Diet‐derived microbial metabolites in health and disease

Roager

Dragsted

2019

Nutrition Bulletin

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The gut microbiota helps us digest food and has been associated with both good health and risk of disease. Although compositions of the gut microbiota are highly divergent, the gut microbiota exhibits a high level of functional redundancy making it difficult to reliably link gut microbiome patterns to health and diet across individuals. Thus, there is a need to move beyond profiling of the gut microbial composition to the assessment of gut microbial metabolic activity in order to expand knowledge on the impact of the gut microbiota on health. Metabolomics has already proven its utility in identifying gut‐derived microbial metabolites, which may be mediators of diet‐induced host–microbial crosstalk important for health. These diet‐derived metabolites include, among many others, the short‐chain fatty acids originating from bacterial degradation of dietary fibres and proteins, secondary bile acids derived from primary bile acids, microbial tryptophan catabolites resulting from proteolysis, imidazole propionate produced from histidine and trimethylamine N‐oxide, a host–microbial co‐metabolite of nutrients such as phosphatidylcholine, choline and L‐carnitine, present in high‐fat foods. These co‐metabolites have been associated with beneficial and detrimental effects in the host. However, the vast majority of metabolites measured by untargeted metabolomics in human blood and excreta remain unknown and may include additional microbial molecules of importance for health. Thus, there is great potential, yet to be explored, for identifying additional diet‐derived microbial products that affect the host. Herein, we review key advances, challenges and limitations in our understanding of diet–microbiome interactions and diet‐derived microbial metabolites in relation to human health and discuss how metabolomics may shed light on inter‐individual differences in dietary responses.

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The fecal metabolome as a functional readout of the gut microbiome

Cited by 549 publications

References 54 publications

Gut microbial‐derived butyrate is inversely associated with IgE responses to allergens in childhood asthma

Gut microbial‐derived butyrate is inversely associated with IgE responses to allergens in childhood asthma

The Gut Microbiome in Pancreatic Disease

Diet‐derived microbial metabolites in health and disease

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