A novel framework for assessing causal effect of microbiome on health: long-term antibiotic usage as an instrument

Assessing causality is undoubtedly one of the key questions in microbiome studies for the upcoming years. Since randomized trials in human subjects are often unethical or difficult to pursue, analytical methods to derive causal effects from observational data deserve attention. As simple covariate a...

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Main Authors: Nele Taba, Krista Fischer, Estonian Biobank Research Team, Elin Org, Oliver Aasmets
Format: Article
Language:English
Published: Taylor & Francis Group 2025-12-01
Series:Gut Microbes
Subjects:
Online Access:https://www.tandfonline.com/doi/10.1080/19490976.2025.2453616
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author Nele Taba
Krista Fischer
Estonian Biobank Research Team
Elin Org
Oliver Aasmets
author_facet Nele Taba
Krista Fischer
Estonian Biobank Research Team
Elin Org
Oliver Aasmets
author_sort Nele Taba
collection DOAJ
description Assessing causality is undoubtedly one of the key questions in microbiome studies for the upcoming years. Since randomized trials in human subjects are often unethical or difficult to pursue, analytical methods to derive causal effects from observational data deserve attention. As simple covariate adjustment is not likely to account for all potential confounders, the idea of instrumental variable (IV) analysis is worth exploiting. Here we propose a novel framework of antibiotic instrumental variable regression (AB-IVR) for estimating the causal relationships between microbiome and various diseases. We rely on the recent studies showing that antibiotic treatment has a cumulative long-term effect on the microbiome, resulting in individuals with higher antibiotic usage to have a more perturbed microbiome. We apply the AB-IVR method on the Estonian Biobank data and show that the microbiome has a causal role in numerous diseases including migraine, depression and irritable bowel syndrome. We show with a plethora of sensitivity analyses that the identified causal effects are robust and propose ways for further methodological developments.
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institution Kabale University
issn 1949-0976
1949-0984
language English
publishDate 2025-12-01
publisher Taylor & Francis Group
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series Gut Microbes
spelling doaj-art-c360a0ecb0a9481eb5159608188f0dae2025-01-24T05:10:33ZengTaylor & Francis GroupGut Microbes1949-09761949-09842025-12-0117110.1080/19490976.2025.2453616A novel framework for assessing causal effect of microbiome on health: long-term antibiotic usage as an instrumentNele Taba0Krista Fischer1Estonian Biobank Research Team2Elin Org3Oliver Aasmets4Estonian Genome Center, Institute of Genomics, University of Tartu, Tartu, EstoniaEstonian Genome Center, Institute of Genomics, University of Tartu, Tartu, EstoniaEstonian Genome Center, Institute of Genomics, University of Tartu, Tartu, EstoniaEstonian Genome Center, Institute of Genomics, University of Tartu, Tartu, EstoniaEstonian Genome Center, Institute of Genomics, University of Tartu, Tartu, EstoniaAssessing causality is undoubtedly one of the key questions in microbiome studies for the upcoming years. Since randomized trials in human subjects are often unethical or difficult to pursue, analytical methods to derive causal effects from observational data deserve attention. As simple covariate adjustment is not likely to account for all potential confounders, the idea of instrumental variable (IV) analysis is worth exploiting. Here we propose a novel framework of antibiotic instrumental variable regression (AB-IVR) for estimating the causal relationships between microbiome and various diseases. We rely on the recent studies showing that antibiotic treatment has a cumulative long-term effect on the microbiome, resulting in individuals with higher antibiotic usage to have a more perturbed microbiome. We apply the AB-IVR method on the Estonian Biobank data and show that the microbiome has a causal role in numerous diseases including migraine, depression and irritable bowel syndrome. We show with a plethora of sensitivity analyses that the identified causal effects are robust and propose ways for further methodological developments.https://www.tandfonline.com/doi/10.1080/19490976.2025.2453616gut microbiomeelectronic health registriesantibioticscausal inference
spellingShingle Nele Taba
Krista Fischer
Estonian Biobank Research Team
Elin Org
Oliver Aasmets
A novel framework for assessing causal effect of microbiome on health: long-term antibiotic usage as an instrument
Gut Microbes
gut microbiome
electronic health registries
antibiotics
causal inference
title A novel framework for assessing causal effect of microbiome on health: long-term antibiotic usage as an instrument
title_full A novel framework for assessing causal effect of microbiome on health: long-term antibiotic usage as an instrument
title_fullStr A novel framework for assessing causal effect of microbiome on health: long-term antibiotic usage as an instrument
title_full_unstemmed A novel framework for assessing causal effect of microbiome on health: long-term antibiotic usage as an instrument
title_short A novel framework for assessing causal effect of microbiome on health: long-term antibiotic usage as an instrument
title_sort novel framework for assessing causal effect of microbiome on health long term antibiotic usage as an instrument
topic gut microbiome
electronic health registries
antibiotics
causal inference
url https://www.tandfonline.com/doi/10.1080/19490976.2025.2453616
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