A Proinflammatory Gut Microbiota Increases Systemic Inflammation and Accelerates Atherosclerosis

Brandsma, Eelke; Kloosterhuis, Niels J.; Koster, Mirjam H.; Dekker, Daphne; Gijbels, Marion J.J.; Velden, Saskia van der; Ríos-Morales, Melany; Faassen, Martijn J.R. van; Loreti, Marco G.; Bruin, Alain de; Fu, Jingyuan; Kuipers, Folkert; Bakker, Barbara M.; Westerterp, Marit; Winther, Menno P.J. de; Hofker, Marten H.; Sluis, Bart van de; Koonen, Debby P. Y.

doi:10.1161/circresaha.118.313234

Cited by 265 publications

(191 citation statements)

References 30 publications

(34 reference statements)

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“…On the other hand, as bacteria regulate the permeability of the intestines, certain species can promote a “leaky gut”, where metabolites associated with the microbes leave the gut and enter the bloodstream. In response, the body produces cytokines and other mediators, effectively launching an inflammatory response [ 66 ]. Similarly, cells within the epithelial tissue of the gut deliver bacterial metabolites to immune cells, promoting inflammation on both a local and systemic scale.…”

Section: Role Of the Gut Microbiota In Immunity And Inflammationmentioning

confidence: 99%

The Gut Microbiota and Inflammation: An Overview

Bander

Nitert

Mousa

et al. 2020

IJERPH

396

234

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The gut microbiota encompasses a diverse community of bacteria that carry out various functions influencing the overall health of the host. These comprise nutrient metabolism, immune system regulation and natural defence against infection. The presence of certain bacteria is associated with inflammatory molecules that may bring about inflammation in various body tissues. Inflammation underlies many chronic multisystem conditions including obesity, atherosclerosis, type 2 diabetes mellitus and inflammatory bowel disease. Inflammation may be triggered by structural components of the bacteria which can result in a cascade of inflammatory pathways involving interleukins and other cytokines. Similarly, by-products of metabolic processes in bacteria, including some short-chain fatty acids, can play a role in inhibiting inflammatory processes. In this review, we aimed to provide an overview of the relationship between the gut microbiota and inflammatory molecules and to highlight relevant knowledge gaps in this field. Based on the current literature, it appears that as the gut microbiota composition differs between individuals and is contingent on a variety of factors like diet and genetics, some individuals may possess bacteria associated with pro-inflammatory effects whilst others may harbour those with anti-inflammatory effects. Recent technological advancements have allowed for better methods of characterising the gut microbiota. Further research to continually improve our understanding of the inflammatory pathways that interact with bacteria may elucidate reasons behind varying presentations of the same disease and varied responses to the same treatment in different individuals. Furthermore, it can inform clinical practice as anti-inflammatory microbes can be employed in probiotic therapies or used to identify suitable prebiotic therapies.

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Section: Role Of the Gut Microbiota In Immunity And Inflammationmentioning

confidence: 99%

The Gut Microbiota and Inflammation: An Overview

Bander

Nitert

Mousa

et al. 2020

IJERPH

396

234

View full text Add to dashboard Cite

show abstract

“…Causal evidence of gut microbiota composition in atherosclerosis is based on fecal microbiota transplantation (FMT) in animal studies. For example, mice transplanted with a more pro-inflammatory gut microbiota composition from Caspase1 -/- mice had 29% larger plaque sizes than controls [ 112 ]. Alternatively, gut microbiota could have indirect proatherogenic effects, by production of pro-atherogenic metabolites.…”

Section: Gut Microbiota In Atherosclerosismentioning

confidence: 99%

Gut Microbiota in Hypertension and Atherosclerosis: A Review

et al. 2020

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Gut microbiota and its metabolites such as short chain fatty acids (SCFA), lipopolysaccharides (LPS), and trimethylamine-N-oxide (TMAO) impact cardiovascular health. In this review, we discuss how gut microbiota and gut metabolites can affect hypertension and atherosclerosis. Hypertensive patients were shown to have lower alpha diversity, lower abundance of SCFA-producing microbiota, and higher abundance of gram-negative bacteria, which are a source of LPS. Animal studies point towards a direct role for SCFAs in blood pressure regulation and show that LPS has pro-inflammatory effects. Translocation of LPS into the systemic circulation is a consequence of increased gut permeability. Atherosclerosis, a multifactorial disease, is influenced by the gut microbiota through multiple pathways. Many studies have focused on the pro-atherogenic role of TMAO, however, it is not clear if this is a causal factor. In addition, gut microbiota play a key role in bile acid metabolism and some interventions targeting bile acid receptors tend to decrease atherosclerosis. Concluding, gut microbiota affect hypertension and atherosclerosis through many pathways, providing a wide range of potential therapeutic targets. Challenges ahead include translation of findings and mechanisms to humans and development of therapeutic interventions that target cardiovascular risk by modulation of gut microbes and metabolites.

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“…Alteration of gut microbiota affects the production of SCFAs, which then participates in the pathophysiology of CVDs. For example, the decrease in SCFA-producing microbiota in Casp1 −/− mice leads to the reduction in microbiota-derived anti-inflammatory SCFAs (propionate, acetate, and butyrate) in the cecum to accelerate inflammation and atherogenesis [88]. Of note, recent clinical work has demonstrated gut microbiota was a diagnostic marker for patients who have coronary artery disease [89,90].…”

Section: Propionate and Propionylationmentioning

confidence: 99%

Short-chain fatty acid, acylation and cardiovascular diseases

2020

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Cardiovascular diseases (CVDs) are the leading cause of morbidity and mortality worldwide. Metabolic dysfunction is a fundamental core mechanism underlying CVDs. Previous studies generally focused on the roles of long-chain fatty acids (LCFAs) in CVDs. However, a growing body of study has implied that short-chain fatty acids (SCFAs: namely propionate, malonate, butyrate, 2-hydroxyisobutyrate (2-HIBA), β-hydroxybutyrate, crotonate, succinate, and glutarate) and their cognate acylations (propionylation, malonylation, butyrylation, 2-hydroxyisobutyrylation, β-hydroxybutyrylation, crotonylation, succinylation, and glutarylation) participate in CVDs. Here, we attempt to provide an overview landscape of the metabolic pattern of SCFAs in CVDs. Especially, we would focus on the SCFAs and newly identified acylations and their roles in CVDs, including atherosclerosis, hypertension, and heart failure. Clinical Science (2020) 134 657-676 https://doi.org/10.1042/CS20200128 cofactors in certain protein acylations, such as propionylation [14], malonylation [15], butyrylation [14], 2-hydroxyisobutyrylation [16], β-hydroxybutyrylation [17], crotonylation [18], succinylation [19], and glutarylation [20]. These discoveries give us a deeper understanding of PTM. Among PTMs, protein acetylation is the earliest discovered and most studied. Similar to protein acetylation, various studies have shown that these newly discovered PTMs are also involved in physiological and pathophysiological processes, including cardiovascular homeostasis.Here in this review, we will summarize SCFAs, protein acylations, and their emerging roles in CVDs, including atherosclerosis, hypertension, and heart failure. The metabolic pattern and FAs in CVDsThe heart is an 'omnivore' , using FAs, glucose, lactate, ketone bodies, and amino acids as metabolic substrates [5,6]. The substrates utilized by the embryonic heart are significantly different from those used by the adult heart. The embryonic heart depends primarily on glycolysis as well as lactate oxidation to produce energy [21]. The newborn and adult heart shift toward the remarkable utilization of FAs to meet cardiac energy demand [5,9]. In failing hearts, a decrease in FA oxidation and an increase in glycolysis are critically involved in cardiac dysfunction [22]. As thus, the metabolic pattern is essential for maintaining cardiac and vascular functions.Diabetes, hypertension, and obesity contribute to heart failure syndrome. Accumulating evidence suggests that hypertension, ischemic hearts, and heart failure induce a shift in substrate toward the remarkable utilization of glucose to generate energy. Despite this shift, the FA oxidation remains to make much energy for the diseased heart [23]. Since FAs are the predominant substrates for cardiomyocytes, alterations in FA metabolism have been implicated as causal in cardiac diseases. FAs within cells and in the circulation are critically involved in cardiometabolic diseases. CVDs are closely associated with lifestyle and metabolic status, which affect circul...

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A Proinflammatory Gut Microbiota Increases Systemic Inflammation and Accelerates Atherosclerosis

Abstract: Supplemental Digital Content is available in the text.

Cited by 265 publications

References 30 publications

The Gut Microbiota and Inflammation: An Overview

The Gut Microbiota and Inflammation: An Overview

Gut Microbiota in Hypertension and Atherosclerosis: A Review

Short-chain fatty acid, acylation and cardiovascular diseases

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