Metabolic programming of the epigenome: host and gut microbial metabolite interactions with host chromatin

Krautkramer, Kimberly A.; Dhillon, Rashpal S.; Denu, John M.; Carey, Hannah V.

doi:10.1016/j.trsl.2017.08.005

Cited by 38 publications

(23 citation statements)

References 223 publications

(279 reference statements)

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“…Accumulating evidence demonstrates that manipulation of the composition of the gut microbiota affects host cardiovascular phenotypes (Kootte, et al, 2012;Sirisinha, 2016). Furthermore, the gastrointestinal tract can be viewed as a diverse and enormous ecosystem that produces a considerable amount of microbial metabolites (Eckburg, et al, 2005), which can be absorbed into the circulation and serve as mediators of gut microbial effects on the host (Furusawa et al, 2013;Seldin, et al, 2016;Krautkramer, et al, 2017). Thus, the gut microbiota contributes directly or indirectly to our health status.…”

Section: Introductionmentioning

confidence: 99%

The gut microbiota and its interactions with cardiovascular disease

Wang

Feng

et al. 2020

Microbial Biotechnology

103

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Summary The intestine is colonized by a considerable community of microorganisms that cohabits within the host and plays a critical role in maintaining host homeostasis. Recently, accumulating evidence has revealed that the gut microbial ecology plays a pivotal role in the occurrence and development of cardiovascular disease (CVD). Moreover, the effects of imbalances in microbe–host interactions on homeostasis can lead to the progression of CVD. Alterations in the composition of gut flora and disruptions in gut microbial metabolism are implicated in the pathogenesis of CVD. Furthermore, the gut microbiota functions like an endocrine organ that produces bioactive metabolites, including trimethylamine/trimethylamine N‐oxide, short‐chain fatty acids and bile acids, which are also involved in host health and disease via numerous pathways. Thus, the gut microbiota and its metabolic pathways have attracted growing attention as a therapeutic target for CVD treatment. The fundamental purpose of this review was to summarize recent studies that have illustrated the complex interactions between the gut microbiota, their metabolites and the development of common CVD, as well as the effects of gut dysbiosis on CVD risk factors. Moreover, we systematically discuss the normal physiology of gut microbiota and potential therapeutic strategies targeting gut microbiota to prevent and treat CVD.

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Section: Introductionmentioning

confidence: 99%

The gut microbiota and its interactions with cardiovascular disease

Wang

Feng

et al. 2020

Microbial Biotechnology

103

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“…Studies have shown that bile acid metabolism is one of the main metabolic pathways that are affected by microbial dysbiosis [56]. Similarly, short chain fatty acids that the exclusive products of microbial metabolism are known to affect the host epigenetic machinery [57,58]. Our metagenomics analysis on the predictive metabolome of the microbial species shows that there is a distinct dominance of energy metabolism pathways (Figure 4).…”

Section: Discussionmentioning

confidence: 77%

Microbial Dysbiosis and polyamine metabolism as predictive markers for early detection of pancreatic cancer

Méndez

Kesh

Arora

et al. 2018

Preprint

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Synopsis:Gut microbiota changes during early stages of pancreatic ductal adenocarcinoma (PDAC) progression and contributes towards host polyamine pool. Both changes can be used as an early predictive marker for PDAC. Short title: Whole genome sequencing of PDAC microbiomeWord count: 4,735 Translational RelevancePancreatic carcinogenesis progresses through pre-cancerous PanIN lesions to invasive cancer. Even though these morphological changes are histologically distinct, imaging techniques are not able to distinguish the pre-invasive PanINs from normal pancreas, making detection of a tumor at a precancerous stage impossible . Thus, majority of cases (85-90%) present with advanced pancreatic cancer at the time of diagnosis. This contributes to the dismal survival rate in this disease. Our study of gut microbiome analysis on KPC mice during tumor progression followed by metabolic reconstruction and experimental validation in human samples indicate that gut-microbiome analysis along with an analysis of the microbial metabolites can be developed as potential biomarkers for detection of PDAC at early stages when histological changes are not yet grossly apparent. AbstractPurpose: The lack of tools for early detection of pancreatic ductal adenocarcinoma (PDAC) is directly correlated to the abysmal survival rate in patients. In addition to several potential detection tools under active investigation, we tested the gut microbiome and its metabolic complement as one of the earliest detection tools that could be useful in patients at high-risk for PDAC. Experimental Design:A combination of 16s pyrosequencing and whole-genome sequencing of gut microbiota was used in a spontaneous genetically engineered PDAC murine model (KRAS G12D TP53 R172H Pdx Cre or KPC). Metabolic reconstruction of microbiome was done using the HUmanN2 pipeline. Serum polyamine levels were measured from murine and patient samples using standard methods. Results:Results showed a progressive Proteobacterial and Firmicutes dominance in gut microbiota in early stages of PDAC development. Upon in silico reconstruction of active metabolic pathways within the altered microbial flora, polyamine and nucleotide biosynthetic pathways were significantly elevated.These metabolic products are known to be actively assimilated by the host and eventually utilized by rapidly dividing cells for proliferation validating their importance in the context of tumorigenesis. In KPC mice, as well as PDAC patients, we show significantly elevated serum polyamine concentration. Therefore, at the early stages of tumorigenesis, the gut microbial composition changes in a way to release metabolites that foster host tumorigenesis, thereby fulfilling the 'vicious cycle hypothesis' of the role of the microbiome in health and disease states. Conclusions:Our results provide a potential, precise, non-invasive tool for early detection of PDAC, which will result in improved outcomes.

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“…Se desarrolla incluso una nueva disciplina, la nutrigenómica, que se enfoca en la relación entre nutrición, disbiosis y epigenética. La modulación epigenética, a nivel principalmente de las histonas, depende de los niveles de metabolitos intermediarios, vitaminas y minerales, los que actúan como sustratos, activadores o inhibidores, así la disbiosis tiene consecuencias directas en expresión génica mediante cambios epigenéticos y desarrollo de enfermedades, sobre todo metabólicas e inmunes (19) , (figura 2).…”

Section: Primer Nivel: Entorno Materno Desfavorableunclassified

Abordaje obstétrico integral de la prematurez y restricción del crecimiento fetal y su relación con las enfermedades crónicas del adulto

Briozzo

Viroga

2020

RMU

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ResumenLos síndromes obstétricos de parto de pretérmino (PP) y restricción de crecimiento fetal (RCIU) comparten mecanismos etiopatogénicos y fisiopatológicos que muchas veces interactúan y se retroalimentan. Desde el punto de vista etiológico, las condiciones específicas que los generan esquemáticamente se pueden clasificar en inflamación, estrés materno, déficit en las condiciones socioeconómicas y vulnerabilidad de derechos, actuación de disruptores endocrinos, alteraciones de la dieta y de la microbiota y afecciones vasculares. Estas condiciones, actuando aislada o más frecuentemente combinadamente, generan un entorno materno desfavorable para el desarrollo del embarazo provocando efectos específicos como son la reacción inmune materna, mediada o no por la presencia de infecciones, la activación del eje hipotálamo-hipófiso-adrenal, la disminución de la acción de la progesterona, las disbiosis, tanto intestinales como vaginales, y la disfunción por envejecimiento placentario. El entorno desfavorable así generado impactará en la unidad útero-placento-fetal, produciendo, bien el PP o bien el RCIU, de acuerdo a la primacía de diferentes respuestas; independientemente de cuál de las respuestas sindromáticas predomine, ambos, el PP y el RCIU, tienen en común el desarrollo del feno-genotipo ahorrador, imprescindible para la sobrevida fetal. El costo de esta modulación epigenética es el aumento de las enfermedades crónicas del adulto, que conceptualmente son enfermedades transmisibles por la vulnerabilidad social donde se desarrolla el ciclo de vida de esas personas. Palabras clave: Retardo del crecimiento fetalNacimiento prematuro Enfermedades crónicas Epigenómica

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Metabolic programming of the epigenome: host and gut microbial metabolite interactions with host chromatin

Cited by 38 publications

References 223 publications

The gut microbiota and its interactions with cardiovascular disease

The gut microbiota and its interactions with cardiovascular disease

Microbial Dysbiosis and polyamine metabolism as predictive markers for early detection of pancreatic cancer

Abordaje obstétrico integral de la prematurez y restricción del crecimiento fetal y su relación con las enfermedades crónicas del adulto

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