Gut physiology and environment explain variations in human gut microbiome composition and metabolism

Nicola Procházková; Martin F. Laursen; Giorgia La Barbera; Eirini Tsekitsidi; Malte S. Jørgensen; Morten A. Rasmussen; Jeroen Raes; Tine R. Licht; Lars O. Dragsted; Henrik M. Roager

doi:10.1038/s41564-024-01856-x

Gut physiology and environment explain variations in human gut microbiome composition and metabolism

Nicola Procházková, Martin F. Laursen, Giorgia La Barbera, Eirini Tsekitsidi, Malte S. Jørgensen, Morten A. Rasmussen, Jeroen Raes, Tine R. Licht, Lars O. Dragsted, Henrik M. Roager^*

^*Corresponding author for this work

Research output: Contribution to journal › Journal article › Research › peer-review

1 Citation (Scopus)

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Abstract

The human gut microbiome is highly personal. However, the contribution of gut physiology and environment to variations in the gut microbiome remains understudied. Here we performed an observational trial using multi-omics to profile microbiome composition and metabolism in 61 healthy adults for 9 consecutive days. We assessed day-to-day changes in gut environmental factors and measured whole-gut and segmental intestinal transit time and pH using a wireless motility capsule in a subset of 50 individuals. We observed substantial daily fluctuations, with intra-individual variations in gut microbiome and metabolism associated with changes in stool moisture and faecal pH, and inter-individual variations accounted for by whole-gut and segmental transit times and pH. Metabolites derived from microbial carbohydrate fermentation correlated negatively with the gut passage time and pH, while proteolytic metabolites and breath methane showed a positive correlation. Finally, we identified associations between segmental transit time/pH and coffee-, diet-, host- and microbial-derived metabolites. Our work suggests that gut physiology and environment are key to understanding the individuality of the human gut microbial composition and metabolism.

Original language	English
Journal	Nature Microbiology
Volume	9
Issue number	12
Pages (from-to)	3210-3225
ISSN	2058-5276
DOIs	https://doi.org/10.1038/s41564-024-01856-x
Publication status	Published - 2024

Bibliographical note

Funding Information:
We thank all the dedicated volunteers who participated in the PRIMA study. We acknowledge our colleague J. Stanstrup for help with the metabolomics data preprocessing, the students A. Seer, I. Barrau, S. H. Kaas and K. L. L. Clemmensen, as well as the bioanalysts S. F. B. Soltane and J. G. J\u00F8rgensen for their assistance during the study visits and laboratory work at the Department of Nutrition Exercise and Sports. We also thank \u00D6. C. Zeki for her help with metabolite annotation and L. L. Stevner for her guidance on General Data Protection Regulation (GDPR) and study protocol writing. Furthermore, we thank K. A. Kristensen (Technical University of Denmark) for the preparation for sequencing. We also thank D. Nguyen (KU Leuven) for the help with flow cytometry and J. F. V. Castellanos (KU Leuven) for the help with QMP analysis. This study was supported by the Novo Nordisk Foundation (NNF19OC0056246; PRIMA\u2014toward Personalized dietary Recommendations based on the Interaction between diet, Microbiome and Abiotic conditions in the gut). L.O.D. was supported by a Semper Ardens grant from the Carlsberg Foundation (CF15-0574). The funders had no role in study design, data collection and analysis, decision to publish or preparation of the manuscript.

Publisher Copyright:
© The Author(s) 2024.

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Gut physiology and environment explain variations in human gut microbiome composition and metabolism. / Procházková, Nicola; Laursen, Martin F.; La Barbera, Giorgia; Tsekitsidi, Eirini; Jørgensen, Malte S.; Rasmussen, Morten A.; Raes, Jeroen; Licht, Tine R.; Dragsted, Lars O.; Roager, Henrik M.

In: Nature Microbiology, Vol. 9, No. 12, 2024, p. 3210-3225.

Research output: Contribution to journal › Journal article › Research › peer-review

Procházková, Nicola ; Laursen, Martin F. ; La Barbera, Giorgia ; Tsekitsidi, Eirini ; Jørgensen, Malte S. ; Rasmussen, Morten A. ; Raes, Jeroen ; Licht, Tine R. ; Dragsted, Lars O. ; Roager, Henrik M. / Gut physiology and environment explain variations in human gut microbiome composition and metabolism. In: Nature Microbiology. 2024 ; Vol. 9, No. 12. pp. 3210-3225.

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title = "Gut physiology and environment explain variations in human gut microbiome composition and metabolism",

abstract = "The human gut microbiome is highly personal. However, the contribution of gut physiology and environment to variations in the gut microbiome remains understudied. Here we performed an observational trial using multi-omics to profile microbiome composition and metabolism in 61 healthy adults for 9 consecutive days. We assessed day-to-day changes in gut environmental factors and measured whole-gut and segmental intestinal transit time and pH using a wireless motility capsule in a subset of 50 individuals. We observed substantial daily fluctuations, with intra-individual variations in gut microbiome and metabolism associated with changes in stool moisture and faecal pH, and inter-individual variations accounted for by whole-gut and segmental transit times and pH. Metabolites derived from microbial carbohydrate fermentation correlated negatively with the gut passage time and pH, while proteolytic metabolites and breath methane showed a positive correlation. Finally, we identified associations between segmental transit time/pH and coffee-, diet-, host- and microbial-derived metabolites. Our work suggests that gut physiology and environment are key to understanding the individuality of the human gut microbial composition and metabolism.",

author = "Nicola Proch{\'a}zkov{\'a} and Laursen, {Martin F.} and {La Barbera}, Giorgia and Eirini Tsekitsidi and J{\o}rgensen, {Malte S.} and Rasmussen, {Morten A.} and Jeroen Raes and Licht, {Tine R.} and Dragsted, {Lars O.} and Roager, {Henrik M.}",

note = "Funding Information: We thank all the dedicated volunteers who participated in the PRIMA study. We acknowledge our colleague J. Stanstrup for help with the metabolomics data preprocessing, the students A. Seer, I. Barrau, S. H. Kaas and K. L. L. Clemmensen, as well as the bioanalysts S. F. B. Soltane and J. G. J\u00F8rgensen for their assistance during the study visits and laboratory work at the Department of Nutrition Exercise and Sports. We also thank \u00D6. C. Zeki for her help with metabolite annotation and L. L. Stevner for her guidance on General Data Protection Regulation (GDPR) and study protocol writing. Furthermore, we thank K. A. Kristensen (Technical University of Denmark) for the preparation for sequencing. We also thank D. Nguyen (KU Leuven) for the help with flow cytometry and J. F. V. Castellanos (KU Leuven) for the help with QMP analysis. This study was supported by the Novo Nordisk Foundation (NNF19OC0056246; PRIMA\u2014toward Personalized dietary Recommendations based on the Interaction between diet, Microbiome and Abiotic conditions in the gut). L.O.D. was supported by a Semper Ardens grant from the Carlsberg Foundation (CF15-0574). The funders had no role in study design, data collection and analysis, decision to publish or preparation of the manuscript. Publisher Copyright: {\textcopyright} The Author(s) 2024.",

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AU - Jørgensen, Malte S.

AU - Rasmussen, Morten A.

AU - Raes, Jeroen

AU - Licht, Tine R.

AU - Dragsted, Lars O.

AU - Roager, Henrik M.

N1 - Funding Information: We thank all the dedicated volunteers who participated in the PRIMA study. We acknowledge our colleague J. Stanstrup for help with the metabolomics data preprocessing, the students A. Seer, I. Barrau, S. H. Kaas and K. L. L. Clemmensen, as well as the bioanalysts S. F. B. Soltane and J. G. J\u00F8rgensen for their assistance during the study visits and laboratory work at the Department of Nutrition Exercise and Sports. We also thank \u00D6. C. Zeki for her help with metabolite annotation and L. L. Stevner for her guidance on General Data Protection Regulation (GDPR) and study protocol writing. Furthermore, we thank K. A. Kristensen (Technical University of Denmark) for the preparation for sequencing. We also thank D. Nguyen (KU Leuven) for the help with flow cytometry and J. F. V. Castellanos (KU Leuven) for the help with QMP analysis. This study was supported by the Novo Nordisk Foundation (NNF19OC0056246; PRIMA\u2014toward Personalized dietary Recommendations based on the Interaction between diet, Microbiome and Abiotic conditions in the gut). L.O.D. was supported by a Semper Ardens grant from the Carlsberg Foundation (CF15-0574). The funders had no role in study design, data collection and analysis, decision to publish or preparation of the manuscript. Publisher Copyright: © The Author(s) 2024.

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N2 - The human gut microbiome is highly personal. However, the contribution of gut physiology and environment to variations in the gut microbiome remains understudied. Here we performed an observational trial using multi-omics to profile microbiome composition and metabolism in 61 healthy adults for 9 consecutive days. We assessed day-to-day changes in gut environmental factors and measured whole-gut and segmental intestinal transit time and pH using a wireless motility capsule in a subset of 50 individuals. We observed substantial daily fluctuations, with intra-individual variations in gut microbiome and metabolism associated with changes in stool moisture and faecal pH, and inter-individual variations accounted for by whole-gut and segmental transit times and pH. Metabolites derived from microbial carbohydrate fermentation correlated negatively with the gut passage time and pH, while proteolytic metabolites and breath methane showed a positive correlation. Finally, we identified associations between segmental transit time/pH and coffee-, diet-, host- and microbial-derived metabolites. Our work suggests that gut physiology and environment are key to understanding the individuality of the human gut microbial composition and metabolism.

AB - The human gut microbiome is highly personal. However, the contribution of gut physiology and environment to variations in the gut microbiome remains understudied. Here we performed an observational trial using multi-omics to profile microbiome composition and metabolism in 61 healthy adults for 9 consecutive days. We assessed day-to-day changes in gut environmental factors and measured whole-gut and segmental intestinal transit time and pH using a wireless motility capsule in a subset of 50 individuals. We observed substantial daily fluctuations, with intra-individual variations in gut microbiome and metabolism associated with changes in stool moisture and faecal pH, and inter-individual variations accounted for by whole-gut and segmental transit times and pH. Metabolites derived from microbial carbohydrate fermentation correlated negatively with the gut passage time and pH, while proteolytic metabolites and breath methane showed a positive correlation. Finally, we identified associations between segmental transit time/pH and coffee-, diet-, host- and microbial-derived metabolites. Our work suggests that gut physiology and environment are key to understanding the individuality of the human gut microbial composition and metabolism.

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