The Gut Microbiota and Unhealthy Aging: Disentangling Cause from Consequence

DeJong, Erica N.; Surette, Michael G.; Bowdish, Dawn M. E.

doi:10.1016/j.chom.2020.07.013

Cited by 197 publications

(150 citation statements)

References 110 publications

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“…from the Netherlands (n = 154) than to that of vaccine non-responders (n = 39); infants from the Netherlands were all assumed to be vaccine responders as ORV seroconversion rates are >90% in infants from Northern The adult gut microbiota is more complex than in infancy (higher levels of diversity) but is also more homogeneous between individuals and, in the absence of external perturbations (such as antibiotics), is generally quite stable. b | As people age, the diversity and stability of the gut microbiota decline 7 . There is also an increased relative abundance of the inflammation-associated Proteobacteria and a decrease in Actinobacteria.…”

Section: Prebioticsmentioning

confidence: 99%

“…These data suggest that specific host factors that vary between LMICs and HICs and at the extremes of life strongly influence the quality and durability of the immune response to vaccination and therefore vaccine effectiveness, although it should be noted that factors other than immunogenicity can also impact vaccine efficacy. Increasing evidence points to the gut microbiota -which is highly variable between individuals, over the course of life 7,8 and between different populations around the world 9 (Box 1) -as a crucial factor modulating immune responses to vaccination 10 . Here, we assess the evidence from clinical cohort studies, Modulation of immune responses to vaccination by the microbiota: implications and potential mechanisms interventional studies and animal models that suggests that the gut microbiota plays an important role in modu lating vaccine immunogenicity.…”

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confidence: 99%

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Modulation of immune responses to vaccination by the microbiota: implications and potential mechanisms

2021

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The need for highly effective vaccines that induce robust and long-lasting immunity has never been more apparent. However, for reasons that are still poorly understood, immune responses to vaccination are highly variable between different individuals and different populations. Furthermore, vaccine immunogenicity is frequently suboptimal in the very populations who are at most risk from infectious disease, including infants, the elderly, and those living in low-income and middle-income countries. Although many factors have the potential to influence vaccine immunogenicity and therefore vaccine effectiveness, increasing evidence from clinical studies and animal models now suggests that the composition and function of the gut microbiota are crucial factors modulating immune responses to vaccination. In this Review, we synthesize this evidence, discuss the immunological mechanisms that potentially mediate these effects and consider the potential of microbiota-targeted interventions to optimize vaccine effectiveness.

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Section: Prebioticsmentioning

confidence: 99%

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confidence: 99%

Modulation of immune responses to vaccination by the microbiota: implications and potential mechanisms

2021

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“…Aging is the most important risk factor for AD. During aging, the gut microbiota composition decreases in diversity and stability ( 42 ). It has been postulated that these changes may evoke hyperstimulation of the immune system resulting in persistent, low-grade inflammation ( 43 ), referred to as “inflammaging” ( 4 ), a phenomenon observed in the elderly.…”

Section: Introductionmentioning

confidence: 99%

Contribution of Gut Microbiota to Immunological Changes in Alzheimer’s Disease

et al. 2021

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Emerging evidence suggests that both central and peripheral immunological processes play an important role in the pathogenesis of Alzheimer’s disease (AD), but regulatory mechanisms remain unknown. The gut microbiota and its key metabolites are known to affect neuroinflammation by modulating the activity of peripheral and brain-resident immune cells, yet an overview on how the gut microbiota contribute to immunological alterations in AD is lacking. In this review, we discuss current literature on microbiota composition in AD patients and relevant animal models. Next, we highlight how microbiota and their metabolites may contribute to peripheral and central immunological changes in AD. Finally, we offer a future perspective on the translation of these findings into clinical practice by targeting gut microbiota to modulate inflammation in AD. Since we find that gut microbiota alterations in AD can induce peripheral and central immunological changes via the release of microbial metabolites, we propose that modulating their composition may alter ongoing inflammation and could therefore be a promising future strategy to fight progression of AD.

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“…10 Reversion of agerelated changes in the micro biome could also be expected following mTOR inhibition, as the immune system plays an important role in maintaining a healthy microbiome. 70 Rapamycin has been found to reduce age-related cancers 32,41 and modify the aged microbiome in mice, 40,51 although it remains to be established whether these effects are mediated by the immune system.…”

Section: Personal Viewmentioning

confidence: 99%

The potential of rapalogs to enhance resilience against SARS-CoV-2 infection and reduce the severity of COVID-19

Bischof

Siow

Zhavoronkov

et al. 2021

The Lancet Healthy Longevity

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COVID-19 disproportionately affects older people, with likelihood of severe complications and death mirroring that of other age-associated diseases. Inhibition of the mechanistic target of rapamycin complex 1 (mTORC1) has been shown to delay or reverse many age-related phenotypes, including declining immune function. Rapamycin (sirolimus) and rapamycin derivatives are US Food and Drug Administration-approved inhibitors of mTORC1 with broad clinical utility and well established dosing and safety profiles. Based on preclinical and clinical evidence, a strong case can be made for immediate large-scale clinical trials to assess whether rapamycin and other mTORC1 inhibitors can prevent COVID-19 infection in these populations and also to determine whether these drugs can improve outcomes in patients with severe COVID-19.

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The Gut Microbiota and Unhealthy Aging: Disentangling Cause from Consequence

Cited by 197 publications

References 110 publications

Modulation of immune responses to vaccination by the microbiota: implications and potential mechanisms

Modulation of immune responses to vaccination by the microbiota: implications and potential mechanisms

Contribution of Gut Microbiota to Immunological Changes in Alzheimer’s Disease

The potential of rapalogs to enhance resilience against SARS-CoV-2 infection and reduce the severity of COVID-19

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