Colonocyte-derived lactate promotes E. coli fitness in the context of inflammation-associated gut microbiota dysbiosis

Savannah J. Taylor; Maria G. Winter; Caroline C. Gillis; Laice Alves da Silva; Amanda L. Dobbins; Matthew K. Muramatsu; Angel G. Jimenez; Rachael B. Chanin; Luisella Spiga; Ernesto M. Llano; Vivian K. Rojas; Jiwoong Kim; Renato L. Santos; Wenhan Zhu; Sebastian E. Winter

doi:10.1186/s40168-022-01389-7

Colonocyte-derived lactate promotes E. coli fitness in the context of inflammation-associated gut microbiota dysbiosis

Savannah J. Taylor, Maria G. Winter, Caroline C. Gillis, Laice Alves da Silva, Amanda L. Dobbins, Matthew K. Muramatsu, Angel G. Jimenez, Rachael B. Chanin, Luisella Spiga, Ernesto M. Llano, Vivian K. Rojas, Jiwoong Kim, Renato L. Santos, Wenhan Zhu, Sebastian E. Winter

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1 Scopus citations

Abstract

Background: Intestinal inflammation disrupts the microbiota composition leading to an expansion of Enterobacteriaceae family members (dysbiosis). Associated with this shift in microbiota composition is a profound change in the metabolic landscape of the intestine. It is unclear how changes in metabolite availability during gut inflammation impact microbial and host physiology. Results: We investigated microbial and host lactate metabolism in murine models of infectious and non-infectious colitis. During inflammation-associated dysbiosis, lactate levels in the gut lumen increased. The disease-associated spike in lactate availability was significantly reduced in mice lacking the lactate dehydrogenase A subunit in intestinal epithelial cells. Commensal E. coli and pathogenic Salmonella, representative Enterobacteriaceae family members, utilized lactate via the respiratory L-lactate dehydrogenase LldD to increase fitness. Furthermore, mice lacking the lactate dehydrogenase A subunit in intestinal epithelial cells exhibited lower levels of inflammation in a model of non-infectious colitis. Conclusions: The release of lactate by intestinal epithelial cells during gut inflammation impacts the metabolism of gut-associated microbial communities. These findings suggest that during intestinal inflammation and dysbiosis, changes in metabolite availability can perpetuate colitis-associated disturbances of microbiota composition. [MediaObject not available: see fulltext.].

Original language	English (US)
Article number	200
Journal	Microbiome
Volume	10
Issue number	1
DOIs	https://doi.org/10.1186/s40168-022-01389-7
State	Published - Dec 2022
Externally published	Yes

Keywords

Gut inflammation
Host-microbe interactions
Lactate metabolism

ASJC Scopus subject areas

Microbiology
Microbiology (medical)

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10.1186/s40168-022-01389-7

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Taylor, S. J., Winter, M. G., Gillis, C. C., Silva, L. A. D., Dobbins, A. L., Muramatsu, M. K., Jimenez, A. G., Chanin, R. B., Spiga, L., Llano, E. M., Rojas, V. K., Kim, J., Santos, R. L., Zhu, W., & Winter, S. E. (2022). Colonocyte-derived lactate promotes E. coli fitness in the context of inflammation-associated gut microbiota dysbiosis. Microbiome, 10(1), [200]. https://doi.org/10.1186/s40168-022-01389-7

Taylor, SJ, Winter, MG, Gillis, CC, Silva, LAD, Dobbins, AL, Muramatsu, MK, Jimenez, AG, Chanin, RB, Spiga, L, Llano, EM, Rojas, VK, Kim, J, Santos, RL, Zhu, W & Winter, SE 2022, 'Colonocyte-derived lactate promotes E. coli fitness in the context of inflammation-associated gut microbiota dysbiosis', Microbiome, vol. 10, no. 1, 200. https://doi.org/10.1186/s40168-022-01389-7

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title = "Colonocyte-derived lactate promotes E. coli fitness in the context of inflammation-associated gut microbiota dysbiosis",

abstract = "Background: Intestinal inflammation disrupts the microbiota composition leading to an expansion of Enterobacteriaceae family members (dysbiosis). Associated with this shift in microbiota composition is a profound change in the metabolic landscape of the intestine. It is unclear how changes in metabolite availability during gut inflammation impact microbial and host physiology. Results: We investigated microbial and host lactate metabolism in murine models of infectious and non-infectious colitis. During inflammation-associated dysbiosis, lactate levels in the gut lumen increased. The disease-associated spike in lactate availability was significantly reduced in mice lacking the lactate dehydrogenase A subunit in intestinal epithelial cells. Commensal E. coli and pathogenic Salmonella, representative Enterobacteriaceae family members, utilized lactate via the respiratory L-lactate dehydrogenase LldD to increase fitness. Furthermore, mice lacking the lactate dehydrogenase A subunit in intestinal epithelial cells exhibited lower levels of inflammation in a model of non-infectious colitis. Conclusions: The release of lactate by intestinal epithelial cells during gut inflammation impacts the metabolism of gut-associated microbial communities. These findings suggest that during intestinal inflammation and dysbiosis, changes in metabolite availability can perpetuate colitis-associated disturbances of microbiota composition. [MediaObject not available: see fulltext.].",

keywords = "Gut inflammation, Host-microbe interactions, Lactate metabolism",

author = "Taylor, {Savannah J.} and Winter, {Maria G.} and Gillis, {Caroline C.} and Silva, {Laice Alves da} and Dobbins, {Amanda L.} and Muramatsu, {Matthew K.} and Jimenez, {Angel G.} and Chanin, {Rachael B.} and Luisella Spiga and Llano, {Ernesto M.} and Rojas, {Vivian K.} and Jiwoong Kim and Santos, {Renato L.} and Wenhan Zhu and Winter, {Sebastian E.}",

note = "Funding Information: Work in SEW{\textquoteright}s lab was funded by the NIH (AI118807, AI166263, AI171537), The Welch Foundation (I-1969-20210327), the Burroughs Wellcome Fund (1017880), and a Research Scholar Grant (RSG-17-048-01-MPC) from the American Cancer Society. SJT and RBC were in part supported by a NIH institutional T32 training grant (AI007520). RBC was in part supported by a NIH F31 fellowship (DK121465). Any opinions, findings, and conclusions or recommendations expressed in this material are those of the author(s) and do not necessarily reflect the views of the funding agencies. The funders had no role in study design, data collection and interpretation, or the decision to submit the work for publication. Funding Information: The authors thank the UT Southwestern Transgenic Core for expert technical assistance in generating LdhaΔIECmice. Publisher Copyright: {\textcopyright} 2022, The Author(s).",

year = "2022",

month = dec,

doi = "10.1186/s40168-022-01389-7",

language = "English (US)",

volume = "10",

journal = "Microbiome",

issn = "2049-2618",

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TY - JOUR

T1 - Colonocyte-derived lactate promotes E. coli fitness in the context of inflammation-associated gut microbiota dysbiosis

AU - Taylor, Savannah J.

AU - Winter, Maria G.

AU - Gillis, Caroline C.

AU - Silva, Laice Alves da

AU - Dobbins, Amanda L.

AU - Muramatsu, Matthew K.

AU - Jimenez, Angel G.

AU - Chanin, Rachael B.

AU - Spiga, Luisella

AU - Llano, Ernesto M.

AU - Rojas, Vivian K.

AU - Kim, Jiwoong

AU - Santos, Renato L.

AU - Zhu, Wenhan

AU - Winter, Sebastian E.

N1 - Funding Information: Work in SEW’s lab was funded by the NIH (AI118807, AI166263, AI171537), The Welch Foundation (I-1969-20210327), the Burroughs Wellcome Fund (1017880), and a Research Scholar Grant (RSG-17-048-01-MPC) from the American Cancer Society. SJT and RBC were in part supported by a NIH institutional T32 training grant (AI007520). RBC was in part supported by a NIH F31 fellowship (DK121465). Any opinions, findings, and conclusions or recommendations expressed in this material are those of the author(s) and do not necessarily reflect the views of the funding agencies. The funders had no role in study design, data collection and interpretation, or the decision to submit the work for publication. Funding Information: The authors thank the UT Southwestern Transgenic Core for expert technical assistance in generating LdhaΔIECmice. Publisher Copyright: © 2022, The Author(s).

PY - 2022/12

Y1 - 2022/12

N2 - Background: Intestinal inflammation disrupts the microbiota composition leading to an expansion of Enterobacteriaceae family members (dysbiosis). Associated with this shift in microbiota composition is a profound change in the metabolic landscape of the intestine. It is unclear how changes in metabolite availability during gut inflammation impact microbial and host physiology. Results: We investigated microbial and host lactate metabolism in murine models of infectious and non-infectious colitis. During inflammation-associated dysbiosis, lactate levels in the gut lumen increased. The disease-associated spike in lactate availability was significantly reduced in mice lacking the lactate dehydrogenase A subunit in intestinal epithelial cells. Commensal E. coli and pathogenic Salmonella, representative Enterobacteriaceae family members, utilized lactate via the respiratory L-lactate dehydrogenase LldD to increase fitness. Furthermore, mice lacking the lactate dehydrogenase A subunit in intestinal epithelial cells exhibited lower levels of inflammation in a model of non-infectious colitis. Conclusions: The release of lactate by intestinal epithelial cells during gut inflammation impacts the metabolism of gut-associated microbial communities. These findings suggest that during intestinal inflammation and dysbiosis, changes in metabolite availability can perpetuate colitis-associated disturbances of microbiota composition. [MediaObject not available: see fulltext.].

AB - Background: Intestinal inflammation disrupts the microbiota composition leading to an expansion of Enterobacteriaceae family members (dysbiosis). Associated with this shift in microbiota composition is a profound change in the metabolic landscape of the intestine. It is unclear how changes in metabolite availability during gut inflammation impact microbial and host physiology. Results: We investigated microbial and host lactate metabolism in murine models of infectious and non-infectious colitis. During inflammation-associated dysbiosis, lactate levels in the gut lumen increased. The disease-associated spike in lactate availability was significantly reduced in mice lacking the lactate dehydrogenase A subunit in intestinal epithelial cells. Commensal E. coli and pathogenic Salmonella, representative Enterobacteriaceae family members, utilized lactate via the respiratory L-lactate dehydrogenase LldD to increase fitness. Furthermore, mice lacking the lactate dehydrogenase A subunit in intestinal epithelial cells exhibited lower levels of inflammation in a model of non-infectious colitis. Conclusions: The release of lactate by intestinal epithelial cells during gut inflammation impacts the metabolism of gut-associated microbial communities. These findings suggest that during intestinal inflammation and dysbiosis, changes in metabolite availability can perpetuate colitis-associated disturbances of microbiota composition. [MediaObject not available: see fulltext.].

KW - Gut inflammation

KW - Host-microbe interactions

KW - Lactate metabolism

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ER -

Colonocyte-derived lactate promotes E. coli fitness in the context of inflammation-associated gut microbiota dysbiosis

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