Vitamin B 12 as a Modulator of Gut Microbial Ecology

Degnan, Patrick H.; Taga, Michiko E.; Goodman, Andrew L.

doi:10.1016/j.cmet.2014.10.002

Cited by 367 publications

(354 citation statements)

References 95 publications

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“…The most well-studied corrinoid variants are cobalamins, with dimethylbenzimidazole (DMB) as the lower axial ligand, and which include vitamin B 12 (or cyanocobalamin, Cbl), which has a CN group as the upper axial ligand. Major sites of corrinoid production are soil and aquatic habitats and within animal gut environments (15). Heterotrophic bacteria, cyanobacteria, and archaea are major sources of corrinoids in marine environments (9,(16)(17)(18).…”

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An Amoebal Grazer of Cyanobacteria Requires Cobalamin Produced by Heterotrophic Bacteria

Beld

Brahamsha

2017

Appl Environ Microbiol

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Amoebae are unicellular eukaryotes that consume microbial prey through phagocytosis, playing a role in shaping microbial food webs. Many amoebal species can be cultivated axenically in rich media or monoxenically with a single bacterial prey species. Here, we characterize heterolobosean amoeba LPG3, a recent natural isolate, which is unable to grow on unicellular cyanobacteria, its primary food source, in the absence of a heterotrophic bacterium, a Pseudomonas species coisolate. To investigate the molecular basis of this requirement for heterotrophic bacteria, we performed a screen using the defined nonredundant transposon library of Vibrio cholerae, which implicated genes in corrinoid uptake and biosynthesis. Furthermore, cobalamin synthase deletion mutations in V. cholerae and the Pseudomonas species coisolate do not support the growth of amoeba LPG3 on cyanobacteria. While cyanobacteria are robust producers of a corrinoid variant called pseudocobalamin, this variant does not support the growth of amoeba LPG3. Instead, we show that it requires cobalamin that is produced by the Pseudomonas species coisolate. The diversity of eukaryotes utilizing corrinoids is poorly understood, and this amoebal corrinoid auxotroph serves as a model for examining predator-prey interactions and micronutrient transfer in bacterivores underpinning microbial food webs.IMPORTANCE Cyanobacteria are important primary producers in aquatic environments, where they are grazed upon by a variety of phagotrophic protists and, hence, have an impact on nutrient flux at the base of microbial food webs. Here, we characterize amoebal isolate LPG3, which consumes cyanobacteria as its primary food source but also requires heterotrophic bacteria as a source of corrinoid vitamins. Amoeba LPG3 specifically requires the corrinoid variant produced by heterotrophic bacteria and cannot grow on cyanobacteria alone, as they produce a different corrinoid variant. This same corrinoid specificity is also exhibited by other eukaryotes, including humans and algae. This amoebal model system allows us to dissect predator-prey interactions to uncover factors that may shape microbial food webs while also providing insight into corrinoid specificity in eukaryotes.KEYWORDS amoeba, corrinoids, microbial interactions, vitamin B 12 U nicellular organisms dominate the eukaryotic phylogenetic tree of life. Although protists make up a significant part of natural microbial communities, they have been largely overlooked and are understudied as simple model eukaryotes (1, 2). While culture-independent metagenomic studies provide insight into the abundance and natural diversity of protists in environmental settings (3), in-depth characterization requires the isolation and cultivation of individual species. A large range of eukaryotic microalgal species have been cultivated and studied, particularly as a source of renewable biofuel compounds in recent years (4, 5); however, besides microalgae, there are only a few protist microbes developed as model systems. Amoebae are...

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An Amoebal Grazer of Cyanobacteria Requires Cobalamin Produced by Heterotrophic Bacteria

Beld

Brahamsha

2017

Appl Environ Microbiol

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“…Anaerostipes caccae (Degnan et al 2014). Pseudo-vitamin B12 from Eubacterium hallii could activate the propionate production by Akkermansia muciniphila via the succinate pathway .…”

Section: Discussionmentioning

confidence: 99%

“…Upon cell lysis, the release of cellular vitamin B12 by Anaerostipes caccae could facilitate methylmalonyl-CoA mutase enzymes (Amuc_1983 and Amuc_1984) of Akkermansia muciniphila to produce propionate (Degnan et al 2014). The upregulation of cobalamin-dependent methylmalonyl-CoA mutase genes in monocultures indicated an attempt by the organism to activate the propionate production pathway in the absence of the essential cofactor (Fig.…”

Section: Amuc-acac Co-cultures (Belzer Et Al 2017) Propionate Is Lmentioning

confidence: 99%

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Cross-feeding interactions of gut symbionts driven by human milk oligosaccharidesand mucins

Chia¹

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Chapter 4Microbial metabolic networks at the mucus layer lead to dietindependent butyrate and vitamin B12 production by intestinal symbionts 71 Chapter 5Deciphering trophic interaction between Akkermansia muciniphila and the butyrogenic gut commensal Anaerostipes caccae using a metatranscriptomic approach 97 Chapter 6General discussion 123 Chapter 7 Thesis summary & Nederlandse samenvatting 143 Appendices References 153Co-author affiliations 179Acknowledgements 183About the author 184List of publications 185 VLAG training activities 186Chapter 1 General introduction and thesis outlineChapter 1 2 General introductionHumans can be considered holobionts, consisting of cells from the host and an even larger number of microorganisms (Postler and Ghosh 2017). The majority of microbes are residing in the gut (Sender et al 2016). The human gut microbiota is a complex ecosystem consisting of bacteria, archaea, microeukaryotes and viruses (Clemente et al 2012). Over 2000 species-level phylotypes (prokaryotes including bacteria and archaea) have been detected for the gut microbiota, with each individual estimated to host at least 160 species (Qin et al 2010, Zoetendal et al 2008. The gut microbiota may impact the well-being of human and susceptibility for diseases by interacting with our metabolic, immune and neurological system (Honda and Littman 2016, Koh et al 2016, Rogers et al 2016. Furthermore, the gut microbiota contributes to a variety of metabolic functions and can be seen as an essential part of our digestive system (El Kaoutari et al 2013). Bacterial symbionts allow the human hosts to utilise inaccessible nutrients by converting complex substrates to short chain fatty acid (SCFA) and vitamins (Fisher et al 2017). Bacterial-derived SCFAs are estimated to contribute about 10% of our daily caloric requirement (Bergman 1990). While all SCFAs are vital for maintaining gut homeostasis, butyrate is of particular interest because it has been attributed to a range of health-promoting functions. Butyrate is the primary energy source for colonic epithelial cells and is associated with the enhancement of colonic barrier function, increase of satiety, pain relief, anti-inflammatory responses, and protection against colorectal cancer (Banasiewicz et al 2013, Bolognini et al 2016, Donohoe et al 2011, Furusawa et al 2013, Goncalves and Martel 2013.Considering the physiological benefits of butyrate to human health, this thesis investigates the microbial interaction of gut symbionts that support butyrate production driven primarily by the host produced glycans in human milk and mucus. Glycans are compounds consisting of an array of glycosidically linked monosaccharides (monosaccharides and disaccharides are collectively termed sugars) such as human milk oligosaccharides (HMOS) and mucins (Varki and Kornfeld 2017). HMOS present in mother milk are the major compositional and functional driver of the infant gut microbiota (Backhed et al 2015). Mucin glycans covering the intestinal lining create a stable niche for bacterial coloni...

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“…Although a common B 12 -binding motif can be used to mine sequences for the presence of novel B 12 -dependent enzymes (2,3), new enzymes that lack the canonical motif continue to be discovered (4). Vitamin B 12 also regulates protein expression by binding to riboswitches (5), which are regulatory RNA.…”

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Elucidation of roles for vitamin B ₁₂ in regulation of folate, ubiquinone, and methionine metabolism

Romine

Rodionov

Maezato

et al. 2017

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

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Only a small fraction of vitamin B 12 -requiring organisms are able to synthesize B 12 de novo, making it a common commodity in microbial communities. Initially recognized as an enzyme cofactor of a few enzymes, recent studies have revealed additional B 12 -binding enzymes and regulatory roles for B 12 . Here we report the development and use of a B 12 -based chemical probe to identify B 12 -binding proteins in a nonphototrophic B 12 -producing bacterium. Two unexpected discoveries resulted from this study. First, we identified a light-sensing B 12 -binding transcriptional regulator and demonstrated that it controls folate and ubiquinone biosynthesis. Second, our probe captured proteins involved in folate, methionine, and ubiquinone metabolism, suggesting that it may play a role as an allosteric effector of these processes. These metabolic processes produce precursors for synthesis of DNA, RNA, and protein. Thereby, B 12 likely modulates growth, and by limiting its availability to auxotrophs, B 12 -producing organisms may facilitate coordination of community metabolism.

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Vitamin B 12 as a Modulator of Gut Microbial Ecology

Cited by 367 publications

References 95 publications

An Amoebal Grazer of Cyanobacteria Requires Cobalamin Produced by Heterotrophic Bacteria

An Amoebal Grazer of Cyanobacteria Requires Cobalamin Produced by Heterotrophic Bacteria

Cross-feeding interactions of gut symbionts driven by human milk oligosaccharidesand mucins

Elucidation of roles for vitamin B ₁₂ in regulation of folate, ubiquinone, and methionine metabolism

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Vitamin B 12 as a Modulator of Gut Microbial Ecology

Cited by 367 publications

References 95 publications

An Amoebal Grazer of Cyanobacteria Requires Cobalamin Produced by Heterotrophic Bacteria

An Amoebal Grazer of Cyanobacteria Requires Cobalamin Produced by Heterotrophic Bacteria

Cross-feeding interactions of gut symbionts driven by human milk oligosaccharidesand mucins

Elucidation of roles for vitamin B 12 in regulation of folate, ubiquinone, and methionine metabolism

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Elucidation of roles for vitamin B ₁₂ in regulation of folate, ubiquinone, and methionine metabolism