Suppression of gut dysbiosis reverses Western diet-induced vascular dysfunction

Battson, Micah L.; Lee, Dustin M.; Jarrell, Dillon K.; Hou, Shuofei; Ecton, Kayl E.; Weir, Tiffany L.; Gentile, Christopher L.

doi:10.1152/ajpendo.00187.2017

Cited by 62 publications

(60 citation statements)

References 70 publications

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“…; Battson et al . ), transfer of microbiota (Karbach et al . ) or targeted dietary interventions (Catry et al .…”

Section: Discussionmentioning

confidence: 99%

“…; Battson et al . ). Group abbreviations are: young control (YC) ( n = 15); young antibiotic‐treated (YA) ( n = 11); old control (OC) ( n = 11); and old antibiotic‐treated (OA) ( N = 10).…”

Section: Methodsmentioning

confidence: 97%

“…DNA was extracted (PureLink Microbiome DNA Purification Kit, A29790; Invitrogen, Carlsbad, CA, USA) and a quantitative PCR was used to determine total microbial DNA counts (reactions optimized for 16s rRNA gene), as described previously (Battson et al . ).…”

Section: Methodsmentioning

confidence: 97%

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Suppression of the gut microbiome ameliorates age‐related arterial dysfunction and oxidative stress in mice

Brunt

Gioscia‐Ryan

Richey

et al. 2019

The Journal of Physiology

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119

109

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Key pointsr Age-related arterial dysfunction, characterized by oxidative stress-and inflammation-mediated endothelial dysfunction and arterial stiffening, is the primary risk factor for cardiovascular diseases.Vienna E. Brunt received her PhD in Human Physiology from the University of Oregon in 2016. She is currently a postdoctoral fellow in Dr D. R. Seals' Integrative Physiology of Aging Laboratory at the University of Colorado Boulder. The studies described in the present study represent work carried out as part of an NIH T32 fellowship through the Division of Cardiology at the University of Colorado Denver. Her long-term research goals are to investigate the efficacy of novel interventions for preserving vascular function with ageing, thereby preventing and/or delaying the progression of cardiovascular diseases. Rachel A. Gioscia-Ryan completed her PhD in the Integrative Physiology of Aging Laboratory at the University of Colorado Boulder in 2016 and is currently in medical school at the University of Michigan. She is pursuing a career as a clinician-scientist conducting integrative physiological studies with the aim of improving human health and patient care. * These authors contributed equally to this work.Abstract Oxidative stress-mediated arterial dysfunction (e.g. endothelial dysfunction and large elastic artery stiffening) is the primary mechanism driving age-related cardiovascular diseases. Accumulating evidence suggests the gut microbiome modulates host physiology because dysregulation ('gut dysbiosis') has systemic consequences, including promotion of oxidative stress. The present study aimed to determine whether the gut microbiome modulates arterial function with ageing. We measured arterial function in young and older mice after 3-4 weeks of treatment with broad-spectrum, poorly-absorbed antibiotics to suppress the gut microbiome. To identify potential mechanistic links between the gut microbiome and age-related arterial dysfunction, we sequenced microbiota from young and older mice and measured plasma levels of the adverse gut-derived metabolite trimethylamine N-oxide (TMAO). In old mice, antibiotics reversed endothelial dysfunction [area-under-the-curve carotid artery dilatation to acetylcholine in young: 345 ± 16 AU vs. old control (OC): 220 ± 34 AU, P < 0.01; vs. old antibiotic-treated (OA): 334 ± 15 AU; P < 0.01 vs. OC] and arterial stiffening (aortic pulse wave velocity in young: 3.62 ± 0.15 m s −1 vs. OC: 4.43 ± 0.38 m s −1 ; vs. OA: 3.52 ± 0.35 m s −1 ; P = 0.03). These improvements were accompanied by lower oxidative stress and greater antioxidant enzyme expression. Ageing altered the abundance of gut microbial taxa associated with gut dysbiosis. Lastly, plasma TMAO was higher with ageing (young: 2.6 ± 0.4 μmol L −1 vs. OC: 7.2 ± 2.0 μmol L −1 ; P < 0.0001) and suppressed by antibiotic treatment (OA: 1.2 ± 0.2 μmol L −1 ; P < 0.0001 vs. OC). The results of the present study provide the first evidence for the gut microbiome being an important mediator of age-related arterial dysfunction and ...

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“…; Battson et al . ), transfer of microbiota (Karbach et al . ) or targeted dietary interventions (Catry et al .…”

Section: Discussionmentioning

confidence: 99%

Section: Methodsmentioning

confidence: 97%

See 1 more Smart Citation

Suppression of the gut microbiome ameliorates age‐related arterial dysfunction and oxidative stress in mice

Brunt

Gioscia‐Ryan

Richey

et al. 2019

The Journal of Physiology

Self Cite

119

109

View full text Add to dashboard Cite

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“…Antibiotic treatment successfully abrogated the gut microbiota and reversed the WDinduced arterial stiffness and endothelial dysfunction. These improvements were accompanied by significant reductions in the LBP, IL-6, nuclear factor-κB, and AGEs [197].…”

Section: Gut-heart Crosstalk and Inflammation In The Development Of Cvdmentioning

confidence: 91%

Gut microbiota and inflammation in chronic kidney disease and their roles in the development of cardiovascular disease

et al. 2018

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The health and proper functioning of the cardiovascular and renal systems largely depend on crosstalk in the gut-kidney-heart/vessel triangle. Recent evidence suggests that the gut microbiota has an integral function in this crosstalk. Mounting evidence indicates that the development of chronic kidney and cardiovascular diseases follows chronic inflammatory processes that are affected by the gut microbiota via various immune, metabolic, endocrine, and neurologic pathways. Additionally, deterioration of the function of the cardiovascular and renal systems has been reported to disrupt the original gut microbiota composition, further contributing to the advancement of chronic cardiovascular and renal diseases. Considering the interaction between the gut microbiota and the renal and cardiovascular systems, we can infer that interventions for the gut microbiota through diet and possibly some medications can prevent/stop the vicious cycle between the gut microbiota and the cardiovascular/renal systems, leading to a decrease in chronic cardiovascular and renal diseases.

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“…Evidence in rodents provides a possible explanation for this phenomenon. In mice, a western diet induces gut dysbiosis that is accompanied by systemic and arterial inflammation and arterial dysfunction (Battson et al., ). These deleterious effects on the arteries were abolished with broad‐spectrum antibiotics, indicating that the microbiome plays a crucial role in inflammation and arterial dysfunction.…”

Section: Observational Evidence Supporting a Relationship Between Agementioning

confidence: 99%

Inflammation as a mediator of arterial ageing

Trott

Fadel

2019

Experimental Physiology

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New Findings What is the topic of this review?This review summarizes and synthesizes what is known about the contribution of inflammation to age‐related arterial dysfunction. What advances does it highlight?This review details observational evidence for the relationship of age‐related inflammation and arterial dysfunction, insight from autoimmune inflammatory diseases and their effects on arterial function, interventional evidence linking inflammation and age‐related arterial dysfunction, insight into age‐related arterial inflammation from preclinical models and interventions to ameliorate age‐related inflammation and arterial dysfunction. Abstract Advanced age is a primary risk factor for cardiovascular disease, the leading cause of death in the industrialized world. Two major components of arterial ageing are stiffening of the large arteries and impaired endothelium‐dependent dilatation in multiple vascular beds. These two alterations are major contributors to the development of overt cardiovascular disease. Increasing inflammation with advanced age is likely to play a role in this arterial dysfunction. The purpose of this review is to synthesize what is known about inflammation and its relationship to age‐related arterial dysfunction. This review discusses both the initial observational evidence for the relationship of age‐related inflammation and arterial dysfunction and the evidence that inflammatory autoimmune diseases are associated with a premature arterial ageing phenotype. We next discuss interventional and mechanistic evidence linking inflammation and age‐related arterial dysfunction in older adults. We also attempt to summarize the relevant evidence from preclinical models. Lastly, we discuss interventions in both humans and animals that have been shown to ameliorate age‐related arterial inflammation and dysfunction. The available evidence provides a strong basis for the role of inflammation in both large artery stiffening and impairment of endothelium‐dependent dilatation; however, the specific inflammatory mediators, the initiating factors and the relative importance of the endothelium, smooth muscle cells, perivascular adipose tissue and immune cells in arterial inflammation are not well understood. With the expansion of the ageing population, ameliorating age‐related arterial inflammation represents an important potential strategy for preserving vascular health in the elderly.

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Suppression of gut dysbiosis reverses Western diet-induced vascular dysfunction

Cited by 62 publications

References 70 publications

Suppression of the gut microbiome ameliorates age‐related arterial dysfunction and oxidative stress in mice

Suppression of the gut microbiome ameliorates age‐related arterial dysfunction and oxidative stress in mice

Gut microbiota and inflammation in chronic kidney disease and their roles in the development of cardiovascular disease

Inflammation as a mediator of arterial ageing

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