Causal relationships among the gut microbiome, short-chain fatty acids and metabolic diseases
Microbiome-wide association studies on large population cohorts have highlighted associations between the gut microbiome and complex traits, including type 2 diabetes (T2D) and obesity1. However, the causal relationships remain largely unresolved. We leveraged information from 952 normoglycemic indi...
| Main Authors: | , , , , , , , , , , , , , , , , |
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| Format: | Journal article |
| Published: |
Springer Nature
2019
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| _version_ | 1826270882479210496 |
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| author | Sanna, S Van Zuydam, NR Mahajan, A Kurilshikov, A Vila, AV Võsa, U Mujagic, Z Masclee, AAM Jonkers, DMAE Oosting, M Joosten, LAB Netea, MG Franke, L Zhernakova, A Fu, J Wijmenga, C McCarthy, M |
| author_facet | Sanna, S Van Zuydam, NR Mahajan, A Kurilshikov, A Vila, AV Võsa, U Mujagic, Z Masclee, AAM Jonkers, DMAE Oosting, M Joosten, LAB Netea, MG Franke, L Zhernakova, A Fu, J Wijmenga, C McCarthy, M |
| author_sort | Sanna, S |
| collection | OXFORD |
| description | Microbiome-wide association studies on large population cohorts have highlighted associations between the gut microbiome and complex traits, including type 2 diabetes (T2D) and obesity1. However, the causal relationships remain largely unresolved. We leveraged information from 952 normoglycemic individuals for whom genome-wide genotyping, gut metagenomic sequence and fecal short-chain fatty acid (SCFA) levels were available2, then combined this information with genome-wide-association summary statistics for 17 metabolic and anthropometric traits. Using bidirectional Mendelian randomization (MR) analyses to assess causality3, we found that the host-genetic-driven increase in gut production of the SCFA butyrate was associated with improved insulin response after an oral glucose-tolerance test (P = 9.8 × 10−5), whereas abnormalities in the production or absorption of another SCFA, propionate, were causally related to an increased risk of T2D (P = 0.004). These data provide evidence of a causal effect of the gut microbiome on metabolic traits and support the use of MR as a means to elucidate causal relationships from microbiome-wide association findings. |
| first_indexed | 2024-03-06T21:47:50Z |
| format | Journal article |
| id | oxford-uuid:4a35177d-3dc5-4784-831e-9d500f1f878b |
| institution | University of Oxford |
| last_indexed | 2024-03-06T21:47:50Z |
| publishDate | 2019 |
| publisher | Springer Nature |
| record_format | dspace |
| spelling | oxford-uuid:4a35177d-3dc5-4784-831e-9d500f1f878b2022-03-26T15:36:15ZCausal relationships among the gut microbiome, short-chain fatty acids and metabolic diseasesJournal articlehttp://purl.org/coar/resource_type/c_dcae04bcuuid:4a35177d-3dc5-4784-831e-9d500f1f878bSymplectic Elements at OxfordSpringer Nature2019Sanna, SVan Zuydam, NRMahajan, AKurilshikov, AVila, AVVõsa, UMujagic, ZMasclee, AAMJonkers, DMAEOosting, MJoosten, LABNetea, MGFranke, LZhernakova, AFu, JWijmenga, CMcCarthy, MMicrobiome-wide association studies on large population cohorts have highlighted associations between the gut microbiome and complex traits, including type 2 diabetes (T2D) and obesity1. However, the causal relationships remain largely unresolved. We leveraged information from 952 normoglycemic individuals for whom genome-wide genotyping, gut metagenomic sequence and fecal short-chain fatty acid (SCFA) levels were available2, then combined this information with genome-wide-association summary statistics for 17 metabolic and anthropometric traits. Using bidirectional Mendelian randomization (MR) analyses to assess causality3, we found that the host-genetic-driven increase in gut production of the SCFA butyrate was associated with improved insulin response after an oral glucose-tolerance test (P = 9.8 × 10−5), whereas abnormalities in the production or absorption of another SCFA, propionate, were causally related to an increased risk of T2D (P = 0.004). These data provide evidence of a causal effect of the gut microbiome on metabolic traits and support the use of MR as a means to elucidate causal relationships from microbiome-wide association findings. |
| spellingShingle | Sanna, S Van Zuydam, NR Mahajan, A Kurilshikov, A Vila, AV Võsa, U Mujagic, Z Masclee, AAM Jonkers, DMAE Oosting, M Joosten, LAB Netea, MG Franke, L Zhernakova, A Fu, J Wijmenga, C McCarthy, M Causal relationships among the gut microbiome, short-chain fatty acids and metabolic diseases |
| title | Causal relationships among the gut microbiome, short-chain fatty acids and metabolic diseases |
| title_full | Causal relationships among the gut microbiome, short-chain fatty acids and metabolic diseases |
| title_fullStr | Causal relationships among the gut microbiome, short-chain fatty acids and metabolic diseases |
| title_full_unstemmed | Causal relationships among the gut microbiome, short-chain fatty acids and metabolic diseases |
| title_short | Causal relationships among the gut microbiome, short-chain fatty acids and metabolic diseases |
| title_sort | causal relationships among the gut microbiome short chain fatty acids and metabolic diseases |
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