Pivotal Roles for pH, Lactate, and Lactate-Utilizing Bacteria in the Stability of a Human Colonic Microbial Ecosystem

ABSTRACT Lactate can be produced by many gut bacteria, but in adults its accumulation in the colon is often an indicator of microbiota perturbation. Using continuous culture anaerobic fermentor systems, we found that lactate concentrations remained low in communities of human colonic bacteria mainta...

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Autores principales:	Shui Ping Wang, Luis A. Rubio, Sylvia H. Duncan, Gillian E. Donachie, Grietje Holtrop, Galiana Lo, Freda M. Farquharson, Josef Wagner, Julian Parkhill, Petra Louis, Alan W. Walker, Harry J. Flint
Formato:	article
Lenguaje:	EN
Publicado:	American Society for Microbiology 2020
Materias:	lactate lactate-utilizing bacteria pH short-chain fatty acids mathematical modeling Microbiology QR1-502
Acceso en línea:	https://doaj.org/article/db6f39ae6a11410391e6b9fe0187e8e1
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spelling	oai:doaj.org-article:db6f39ae6a11410391e6b9fe0187e8e12021-12-02T19:46:19ZPivotal Roles for pH, Lactate, and Lactate-Utilizing Bacteria in the Stability of a Human Colonic Microbial Ecosystem10.1128/mSystems.00645-202379-5077https://doaj.org/article/db6f39ae6a11410391e6b9fe0187e8e12020-10-01T00:00:00Zhttps://journals.asm.org/doi/10.1128/mSystems.00645-20https://doaj.org/toc/2379-5077ABSTRACT Lactate can be produced by many gut bacteria, but in adults its accumulation in the colon is often an indicator of microbiota perturbation. Using continuous culture anaerobic fermentor systems, we found that lactate concentrations remained low in communities of human colonic bacteria maintained at pH 6.5, even when dl-lactate was infused at 10 or 20 mM. In contrast, lower pH (5.5) led to periodic lactate accumulation following lactate infusion in three fecal microbial communities examined. Lactate accumulation was concomitant with greatly reduced butyrate and propionate production and major shifts in microbiota composition, with Bacteroidetes and anaerobic Firmicutes being replaced by Actinobacteria, lactobacilli, and Proteobacteria. Pure-culture experiments confirmed that Bacteroides and Firmicutes isolates were susceptible to growth inhibition by relevant concentrations of lactate and acetate, whereas the lactate-producer Bifidobacterium adolescentis was resistant. To investigate system behavior further, we used a mathematical model (microPop) based on 10 microbial functional groups. By incorporating differential growth inhibition, our model reproduced the chaotic behavior of the system, including the potential for lactate infusion both to promote and to rescue the perturbed system. The modeling revealed that system behavior is critically dependent on the proportion of the community able to convert lactate into butyrate or propionate. Communities with low numbers of lactate-utilizing bacteria are inherently less stable and more prone to lactate-induced perturbations. These findings can help us to understand the consequences of interindividual microbiota variation for dietary responses and microbiota changes associated with disease states. IMPORTANCE Lactate is formed by many species of colonic bacteria, and can accumulate to high levels in the colons of inflammatory bowel disease subjects. Conversely, in healthy colons lactate is metabolized by lactate-utilizing species to the short-chain fatty acids butyrate and propionate, which are beneficial for the host. Here, we investigated the impact of continuous lactate infusions (up to 20 mM) at two pH values (6.5 and 5.5) on human colonic microbiota responsiveness and metabolic outputs. At pH 5.5 in particular, lactate tended to accumulate in tandem with decreases in butyrate and propionate and with corresponding changes in microbial composition. Moreover, microbial communities with low numbers of lactate-utilizing bacteria were inherently less stable and therefore more prone to lactate-induced perturbations. These investigations provide clear evidence of the important role these lactate utilizers may play in health maintenance. These should therefore be considered as potential new therapeutic probiotics to combat microbiota perturbations.Shui Ping WangLuis A. RubioSylvia H. DuncanGillian E. DonachieGrietje HoltropGaliana LoFreda M. FarquharsonJosef WagnerJulian ParkhillPetra LouisAlan W. WalkerHarry J. FlintAmerican Society for Microbiologyarticlelactatelactate-utilizing bacteriapHshort-chain fatty acidsmathematical modelingMicrobiologyQR1-502ENmSystems, Vol 5, Iss 5 (2020)
institution	DOAJ
collection	DOAJ
language	EN
topic	lactate lactate-utilizing bacteria pH short-chain fatty acids mathematical modeling Microbiology QR1-502
spellingShingle	lactate lactate-utilizing bacteria pH short-chain fatty acids mathematical modeling Microbiology QR1-502 Shui Ping Wang Luis A. Rubio Sylvia H. Duncan Gillian E. Donachie Grietje Holtrop Galiana Lo Freda M. Farquharson Josef Wagner Julian Parkhill Petra Louis Alan W. Walker Harry J. Flint Pivotal Roles for pH, Lactate, and Lactate-Utilizing Bacteria in the Stability of a Human Colonic Microbial Ecosystem
description	ABSTRACT Lactate can be produced by many gut bacteria, but in adults its accumulation in the colon is often an indicator of microbiota perturbation. Using continuous culture anaerobic fermentor systems, we found that lactate concentrations remained low in communities of human colonic bacteria maintained at pH 6.5, even when dl-lactate was infused at 10 or 20 mM. In contrast, lower pH (5.5) led to periodic lactate accumulation following lactate infusion in three fecal microbial communities examined. Lactate accumulation was concomitant with greatly reduced butyrate and propionate production and major shifts in microbiota composition, with Bacteroidetes and anaerobic Firmicutes being replaced by Actinobacteria, lactobacilli, and Proteobacteria. Pure-culture experiments confirmed that Bacteroides and Firmicutes isolates were susceptible to growth inhibition by relevant concentrations of lactate and acetate, whereas the lactate-producer Bifidobacterium adolescentis was resistant. To investigate system behavior further, we used a mathematical model (microPop) based on 10 microbial functional groups. By incorporating differential growth inhibition, our model reproduced the chaotic behavior of the system, including the potential for lactate infusion both to promote and to rescue the perturbed system. The modeling revealed that system behavior is critically dependent on the proportion of the community able to convert lactate into butyrate or propionate. Communities with low numbers of lactate-utilizing bacteria are inherently less stable and more prone to lactate-induced perturbations. These findings can help us to understand the consequences of interindividual microbiota variation for dietary responses and microbiota changes associated with disease states. IMPORTANCE Lactate is formed by many species of colonic bacteria, and can accumulate to high levels in the colons of inflammatory bowel disease subjects. Conversely, in healthy colons lactate is metabolized by lactate-utilizing species to the short-chain fatty acids butyrate and propionate, which are beneficial for the host. Here, we investigated the impact of continuous lactate infusions (up to 20 mM) at two pH values (6.5 and 5.5) on human colonic microbiota responsiveness and metabolic outputs. At pH 5.5 in particular, lactate tended to accumulate in tandem with decreases in butyrate and propionate and with corresponding changes in microbial composition. Moreover, microbial communities with low numbers of lactate-utilizing bacteria were inherently less stable and therefore more prone to lactate-induced perturbations. These investigations provide clear evidence of the important role these lactate utilizers may play in health maintenance. These should therefore be considered as potential new therapeutic probiotics to combat microbiota perturbations.
format	article
author	Shui Ping Wang Luis A. Rubio Sylvia H. Duncan Gillian E. Donachie Grietje Holtrop Galiana Lo Freda M. Farquharson Josef Wagner Julian Parkhill Petra Louis Alan W. Walker Harry J. Flint
author_facet	Shui Ping Wang Luis A. Rubio Sylvia H. Duncan Gillian E. Donachie Grietje Holtrop Galiana Lo Freda M. Farquharson Josef Wagner Julian Parkhill Petra Louis Alan W. Walker Harry J. Flint
author_sort	Shui Ping Wang
title	Pivotal Roles for pH, Lactate, and Lactate-Utilizing Bacteria in the Stability of a Human Colonic Microbial Ecosystem
title_short	Pivotal Roles for pH, Lactate, and Lactate-Utilizing Bacteria in the Stability of a Human Colonic Microbial Ecosystem
title_full	Pivotal Roles for pH, Lactate, and Lactate-Utilizing Bacteria in the Stability of a Human Colonic Microbial Ecosystem
title_fullStr	Pivotal Roles for pH, Lactate, and Lactate-Utilizing Bacteria in the Stability of a Human Colonic Microbial Ecosystem
title_full_unstemmed	Pivotal Roles for pH, Lactate, and Lactate-Utilizing Bacteria in the Stability of a Human Colonic Microbial Ecosystem
title_sort	pivotal roles for ph, lactate, and lactate-utilizing bacteria in the stability of a human colonic microbial ecosystem
publisher	American Society for Microbiology
publishDate	2020
url	https://doaj.org/article/db6f39ae6a11410391e6b9fe0187e8e1
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Pivotal Roles for pH, Lactate, and Lactate-Utilizing Bacteria in the Stability of a Human Colonic Microbial Ecosystem

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