Short-chain fatty acid production in accessible and inaccessible body pools as assessed by novel stable tracer pulse approach is reduced by aging independent of presence of COPD

Kirschner, Sarah; Ghane, Parisa; Park, Jaekwan K; Simbo, S; Ivanov, Ivan; Braga-Neto, Ulisses; Have, Gabriella A.M. Ten; Thaden, John J.; Engelen, M.P.; Deutz, Nicolaas E. P.

doi:10.1016/j.metabol.2023.155399

Cited by 3 publications

(2 citation statements)

References 35 publications

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“…Having characterized the potential interactions between the host and the microbiome in-depth, we next investigated how they changed in the context of aging. We observed significant decreases in microbiome metabolic activity and growth, including in microbial production of the short-chain fatty acid butyrate, consistent with previous observations of reduced butyrate levels in the serum of aged mice 41 and humans 63 . In contrast, metabolic modeling predicted increased production of the proinflammatory metabolite succinate 64,65 , which has been previously shown to be an indicator for a dysbiotic gut environment 49 and is consistent with the deregulation of succinate metabolism and succinate-dependent regulatory pathways involving the aging-regulator SIRT5 on the host side 66 .…”

Section: Discussionsupporting

confidence: 91%

Metabolic modeling reveals the aging-associated decline of host-microbiome metabolic interactions in mice

Best,

Dost,

Esser

et al. 2024

Preprint

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Aging is the predominant cause of morbidity and mortality in industrialized countries. The specific molecular mechanisms that drive aging are poorly understood, especially the contribution of the microbiota in these processes. Here, we combined multi-omics with metabolic modeling in mice to comprehensively characterize host-microbiome interactions and how they are affected by aging. Our findings reveal a complex dependency of host metabolism on microbial functions, including previously known as well as novel interactions. We observed a pronounced reduction in metabolic activity within the aging microbiome, which we attribute to reduced beneficial interactions in the microbial community and a reduction in its metabolic output. These microbial changes coincided with a corresponding downregulation of key host pathways predicted by our model to be dependent on the microbiome that are crucial for maintaining intestinal barrier function, cellular replication, and homeostasis. Our results elucidate microbiome-host interactions that potentially influence host aging processes, focusing on microbial nucleotide metabolism as a pivotal factor in aging dynamics. These pathways could serve as future targets for the development of microbiome-based therapies against aging.

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Section: Discussionsupporting

confidence: 91%

Metabolic modeling reveals the aging-associated decline of host-microbiome metabolic interactions in mice

Best,

Dost,

Esser

et al. 2024

Preprint

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“…In rodents, ovariectomy reduced SCFA metabolite bioavailability, which was partially restored with Lactobacillus probiotic or high-fiber diet administration (Chen et al, 2021). Clinical studies have also determined that aging and menopause are associated with decreased SCFA (Kirschner et al, 2023). A cross-sectional study investigating both the plasma and fecal SCFA showed that circulating (but not fecal) butyrate and propionate (but not acetate) were inversely related to BMI (Muller et al, 2019).…”

Section: Short Chain Fatty Acidsmentioning

confidence: 99%

The microbiome: a link between obesity and breast cancer risk

Gaber,

Arnone,

Vidi

et al. 2024

Front. Microbiomes

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Globally, breast cancer is the leading cause of cancer incidence and mortality among all female cancers. Hereditary factors only account for 5-10% of breast cancers, highlighting the importance of non-hereditary factors, such as obesity. The increasing prevalence of obesity underscores the need to understand its contribution to breast cancer risk. Multiple mechanisms may mediate pro-carcinogenic effects of obesity, including altered adipokine levels, local and systemic inflammation, disruption of insulin and insulin-like growth factor signaling, increased estrogen levels, and alterations of the microbiome. In this review, we focus on the link between gut microbiome alterations and breast cancer risk in the context of obesity. First, we discuss how obesity influences the gut microbiome. Next, we describe the effect of such microbiome alterations on breast carcinogenesis, highlighting underlying molecular mechanisms. Finally, we review preclinical data on the interactions between host and bacteria, current challenges to study the obesity-microbiome connection, and future perspectives in this field.

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