Microbiota derived short chain fatty acids promote histone crotonylation in the colon through histone deacetylases

Fellows, Rachel; Denizot, Jérémy; Stellato, Claudia; Cuomo, Alessandro; Jain, Payal; Stoyanova, Elena; Balázsi, Szabina; Hajnády, Zoltán; Liebert, Anke; Kazakevych, Juri; Blackburn, Hector; Corrêa, Renan Oliveira; Fachi, José Luís; Sato, Fábio Takeo; Ribeiro, Willian R.; Ferreira, Caroline M.; Perée, Hélène; Spagnuolo, Mariangela; Mattiuz, Raphaël; Matolcsi, Csaba; Guedes, Joana; Clark, Jonathan; Veldhoen, Marc; Bonaldi, Tiziana; Vinolo, Marco Aurélio Ramirez; Varga‐Weisz, Patrick

doi:10.1038/s41467-017-02651-5

Cited by 390 publications

(322 citation statements)

References 51 publications

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“…Physiologically, butyrate is associated with the enhancement of colonic barrier function and it could regulate host immune and metabolic state by signalling through G-protein-coupled receptors (GPR) and by inhibiting histone deacetylase (HDAC) (Bolognini et al 2016, Fellows et al 2018, Koh et al 2016.…”

Section: Discussionmentioning

confidence: 99%

“…Besides, SCFAs signalling through GPR109A exerts antiinflammatory and anti-tumorigenic responses (Macia et al 2015). Butyrate and propionate to a lesser extent, can also be involved in the epigenetic regulation of host gene expression by inhibiting histone deacetylase (HDAC) (Fellows et al 2018).…”

Section: Comparative Genomics Reveal Thatmentioning

confidence: 99%

“…Physiologically, butyrate is associated with the enhancement of colonic barrier function, increase satiety, pain relief, anti-inflammation, 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. Also, it can regulate host immune and metabolic states by signalling through G-protein-coupled receptors (GPR) and by inhibiting histone deacetylase (HDAC) (Bolognini et al 2016, Fellows et al 2018, Koh et al 2016. Most of the mechanistic evidence for the effect of butyrate is generated through studies with adults.…”

Section: The Importance Of Butyrate Production By the Gut Microbiotamentioning

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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Section: Discussionmentioning

confidence: 99%

Section: Comparative Genomics Reveal Thatmentioning

confidence: 99%

Section: The Importance Of Butyrate Production By the Gut Microbiotamentioning

confidence: 99%

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

Chia¹

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“…SCFA have been linked to multiple beneficial effects on host energy metabolism . One of the identified SCFA mechanisms of action, which connects cellular metabolism to gene expression, is inhibition of histone deacetylases . Post‐translational histone modifications are known to be important regulators of gene expression.…”

Section: The Gut Environmentmentioning

confidence: 99%

Reconceptualizing anorexia nervosa

Bulik

Flatt

Abbaspour

et al. 2019

Psychiatry Clin Neurosci

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Anorexia nervosa (AN) has one of the highest mortality rates of any psychiatric disorder. Treatments are often ineffective and relapse is common. Most research attempting to understand the underlying causes and maintenance factors of AN has focused on environmental contributions, yet there is much to be explored in terms of biological risk and maintenance factors. In this paper, we focus primarily on AN research related to genetics and the complex microbial community in the gut (intestinal microbiota), and how these impact our conceptualization of this disorder. Emerging research identifying significant negative genetic correlations between AN and obesity suggests that the conditions may represent ‘metabolic bookends’. The identification of underlying biological mechanisms may provide both insight into extreme weight dysregulation on both ends of the spectrum and new possible points of entry for AN treatment. Additionally, the reported microbial imbalance (dysbiosis) in the gut microbiota in AN patients, potentially due to a nutrient‐ and energy‐deprived gut environment, implies alterations in functional and metabolic capacity of the gut microbiome. The extent to which AN and obesity can also be considered to be ‘microbiome bookends’ requires further investigation. Finally, we discuss ongoing and future AN projects exploring the interplay between host genomics, the environment, and cumulative microbial genomes (microbiome) as well as interventions at the microbial and gut level.

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“…Human-dwelling microbes are subject to the normal rules of ecology, and their activities can influence our physiology and psyche by: regulation of host gene expression, modulation of host epigenetic mechanisms, immune maturation and modulation, breakdown of hormones, release of signalling molecules, etc. (Sommer and Bäckhed 2013;Schirmer et al, 2016;Fellows et al, 2018). This growing realization of the importance of microbe-human interactions, coupled with developments in highthroughput sequencing, has led to a deluge of correlations between an organism's health and the composition of its microbiome.…”

Section: Dealing With Antibiotic Resistancementioning

confidence: 99%

2038 – When microbes rule the Earth

McGenity

2018

Environmental Microbiology

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Microbiota derived short chain fatty acids promote histone crotonylation in the colon through histone deacetylases

Cited by 390 publications

References 51 publications

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

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

Reconceptualizing anorexia nervosa

2038 – When microbes rule the Earth

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