The role of pH in determining the species composition of the human colonic microbiota

Duncan, Sylvia H.; Louis, Petra; Thomson, John; Flint, Harry J.

doi:10.1111/j.1462-2920.2009.01931.x

Cited by 622 publications

(487 citation statements)

References 52 publications

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“…Confirming previous results (15), Bt and Er are found to respond differently to changes in environmental pH values. Although Bt can grow faster than Er at neutral pH, Er has a less sensitive growth response to a drop in pH than Bt, and is thus less affected by the acidification caused by fermentative growth (Fig.…”

Section: Significancesupporting

confidence: 80%

“…1D). It has been shown that the pH dependence of these two strains is qualitatively representative of many abundant species in their respective phyla; Duncan et al (15) have tested 8 strains of the phylum Bacteroidetes, and 20 strains of the phylum Firmicutes at three different pH values, and consistently reported a less severe effect of low pH on Firmicutes. To model a coarse-grained gut microbiota composed of the two dominant phyla, the Bacteroidetes and the Firmicutes (6), we used the experimental parameters derived for Bt and Er ( Fig.…”

Section: Significancementioning

confidence: 99%

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Effect of water flow and chemical environment on microbiota growth and composition in the human colon

Cremer

Arnoldini

Hwa

2017

Proc. Natl. Acad. Sci. U.S.A.

143

192

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The human gut harbors a dynamic microbial community whose composition bears great importance for the health of the host. Here, we investigate how colonic physiology impacts bacterial growth, which ultimately dictates microbiota composition. Combining measurements of bacterial physiology with analysis of published data on human physiology into a quantitative, comprehensive modeling framework, we show how water flow in the colon, in concert with other physiological factors, determine the abundances of the major bacterial phyla. Mechanistically, our model shows that local pH values in the lumen, which differentially affect the growth of different bacteria, drive changes in microbiota composition. It identifies key factors influencing the delicate regulation of colonic pH, including epithelial water absorption, nutrient inflow, and luminal buffering capacity, and generates testable predictions on their effects. Our findings show that a predictive and mechanistic understanding of microbial ecology in the gut is possible. Such predictive understanding is needed for the rational design of intervention strategies to actively control the microbiota. T he human gut microbiota is composed of trillions of bacterial cells (1-4) from several hundred species (1-3, 5, 6). Over the last two decades, a multitude of studies have shown a strong impact of human health status on the composition of this microbiota, and in turn a strong effect of microbiota composition on host physiology has also been confirmed (7-9). Various intervention strategies are being investigated to modify the microbiota composition via prebiotics and probiotics (10). Despite this importance for human health, little is known about how the microbiota composition is shaped by the interplay between human and bacterial physiology in the gut.In this study, we present a physiological model that quantitatively describes this host-microbiota interplay. Our model is based on a hydrodynamic perspective, which posits that bacterial densities reached in the colon result from a dynamic balance between bacterial growth, flow through the colon, and peristaltic mixing (11). To build the present model, we extensively analyzed literature data on human gut physiology to obtain quantitative estimates for a range of relevant host parameters. We further characterized the rates of bacterial growth, carbohydrate consumption, and fermentation product excretion for representatives of the two dominant bacteria phyla, Bacteroidetes and Firmicutes, that typically make up more than 90% of the bacterial cells observed in the gut (6).Combining these aspects of human and bacterial physiology into a coarse-grained mathematical model allowed us to study bacterial growth dynamics in the human gut. Without resorting to ad hoc fitting parameters, model results are in quantitative agreement with available data on key observables of human gut physiology. We find that changes in pH values in the colon that are due to the secretion of acidic fermentation products and shaped by human physiology (such a...

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Section: Significancesupporting

confidence: 80%

Section: Significancementioning

confidence: 99%

Effect of water flow and chemical environment on microbiota growth and composition in the human colon

Cremer

Arnoldini

Hwa

2017

Proc. Natl. Acad. Sci. U.S.A.

143

192

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“…This in vivo enrichment of Firmicutes in mucus, although sometimes less strong as during our in vitro study, suggests that similar forces may drive the mucosal microbiota composition in vivo and in vitro, likely to include selection of specific groups that adhere to mucins (Leitch et al, 2007) or insoluble substrates in general (Walker et al, 2008). Furthermore, as opposed to the luminal content where the pH was maintained constant, local accumulation of acids in mucus may cause a lower pH, selecting for Firmicutes over Bacteroidetes and Proteobacteria (Duncan et al, 2009). In addition, mucins may also serve as a growth substrate for butyrate-producing Firmicutes, possibly via cross-feeding with mucin-degrading microbes that deliver partial breakdown products, acetate and/or lactate (Belzer and de Vos 2012), similar as reported for fructo-oligosaccharides (Belenguer et al, 2006;Falony et al, 2006).…”

Section: Discussionmentioning

confidence: 98%

Butyrate-producing Clostridium cluster XIVa species specifically colonize mucins in an in vitro gut model

et al. 2012

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The human gut is colonized by a complex microbiota with multiple benefits. Although the surfaceattached, mucosal microbiota has a unique composition and potential to influence human health, it remains difficult to study in vivo. Therefore, we performed an in-depth microbial characterization (human intestinal tract chip (HITChip)) of a recently developed dynamic in vitro gut model, which simulates both luminal and mucosal gut microbes (mucosal-simulator of human intestinal microbial ecosystem (M-SHIME)). Inter-individual differences among human subjects were confirmed and microbial patterns unique for each individual were preserved in vitro. Furthermore, in correspondence with in vivo studies, Bacteroidetes and Proteobacteria were enriched in the luminal content while Firmicutes rather colonized the mucin layer, with Clostridium cluster XIVa accounting for almost 60% of the mucin-adhered microbiota. Of the many acetate and/or lactate-converting butyrate producers within this cluster, Roseburia intestinalis and Eubacterium rectale most specifically colonized mucins. These 16S rRNA gene-based results were confirmed at a functional level as butyryl-CoA:acetate-CoA transferase gene sequences belonged to different species in the luminal as opposed to the mucin-adhered microbiota, with Roseburia species governing the mucosal butyrate production. Correspondingly, the simulated mucosal environment induced a shift from acetate towards butyrate. As not only inter-individual differences were preserved but also because compared with conventional models, washout of relevant mucin-adhered microbes was avoided, simulating the mucosal gut microbiota represents a breakthrough in modeling and mechanistically studying the human intestinal microbiome in health and disease. Finally, as mucosal butyrate producers produce butyrate close to the epithelium, they may enhance butyrate bioavailability, which could be useful in treating diseases, such as inflammatory bowel disease.

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“…In addition to the type of carbohydrate available to the microbiota, other factors also have to be considered with regard to propionate production in the gut. Thus, pH is an important determinant in the competition between Bacteroidetes and Firmicutes (Walker et al, 2005;Duncan et al, 2009), and the level of propionate production in Bacteroidetes is dependent on carbon dioxide levels (Macfarlane and Gibson, 1997).…”

mentioning

confidence: 99%

Phylogenetic distribution of three pathways for propionate production within the human gut microbiota

et al. 2014

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Propionate is produced in the human large intestine by microbial fermentation and may help maintain human health. We have examined the distribution of three different pathways used by bacteria for propionate formation using genomic and metagenomic analysis of the human gut microbiota and by designing degenerate primer sets for the detection of diagnostic genes for these pathways. Degenerate primers for the acrylate pathway (detecting the lcdA gene, encoding lactoylCoA dehydratase) together with metagenomic mining revealed that this pathway is restricted to only a few human colonic species within the Lachnospiraceae and Negativicutes. The operation of this pathway for lactate utilisation in Coprococcus catus (Lachnospiraceae) was confirmed using stable isotope labelling. The propanediol pathway that processes deoxy sugars such as fucose and rhamnose was more abundant within the Lachnospiraceae (based on the pduP gene, which encodes propionaldehyde dehydrogenase), occurring in relatives of Ruminococcus obeum and in Roseburia inulinivorans. The dominant source of propionate from hexose sugars, however, was concluded to be the succinate pathway, as indicated by the widespread distribution of the mmdA gene that encodes methylmalonyl-CoA decarboxylase in the Bacteroidetes and in many Negativicutes. In general, the capacity to produce propionate or butyrate from hexose sugars resided in different species, although two species of Lachnospiraceae (C. catus and R. inulinivorans) are now known to be able to switch from butyrate to propionate production on different substrates. A better understanding of the microbial ecology of short-chain fatty acid formation may allow modulation of propionate formation by the human gut microbiota.

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The role of pH in determining the species composition of the human colonic microbiota

Cited by 622 publications

References 52 publications

Effect of water flow and chemical environment on microbiota growth and composition in the human colon

Effect of water flow and chemical environment on microbiota growth and composition in the human colon

Butyrate-producing Clostridium cluster XIVa species specifically colonize mucins in an in vitro gut model

Phylogenetic distribution of three pathways for propionate production within the human gut microbiota

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