Linking the Triad of Telomere Length, Inflammation, and Gut Dysbiosis in the Manifestation of Depression

Abstract

Telomere length is an indispensable marker for cellular and biological aging, and it also represents an individual's physical and mental health status. Telomere shortening has been observed in chronic inflammatory conditions, which in turn accelerates aging and risk for psychiatric disorders, including depression. Considering the influence of inflammation and telomere shortening on the gut−brain axis, herein we describe a plausible interplay between telomere attrition, inflammation, and gut dysbiosis in the neurobiology of depression. Telomere shortening and hyperinflammation are well reported in depression. A negative impact of augmented inflammation has been noted on the intestinal permeability and microbial consortia and their byproducts in depressive patients. Moreover, gut dysbiosis provokes host-immune responses. As the gut microbiome is gaining importance in the manifestation and management of depression, herein we discuss whether telomere attrition is connected with the perturbation of commensal microflora. We also describe a pathological connection of cortisol with hyperinflammation, telomere shortening, and gut dysbiosis occurring in depression. This review summarizes how the triad of telomere attrition, inflammation, and gut dysbiosis is interconnected and modulates the risk for depression by regulating the systemic cortisol levels.

SCFAs Supplementation Rescues Anxiety- and Depression-like Phenotypes Generated by Fecal Engraftment of Treatment-Resistant Depression Rats

“…The bidirectional crosstalk between proinflammatory cytokines and CRF is also well supported . CRF plays a key role in activating the HPA axis and hypersecretion of stress hormones, such as corticosterone, which is closely linked to regulating anxiety, depression, and anhedonia. , In our study, TRD and TRD-FMT rats exhibited an increased population of CRF neurons in the PVN and elevated levels of corticosterone in the systemic circulation. When these animals were treated with SCFAs reverted the increased density of CRF neurons and plasma concentration of corticosterone.…”

“…It has been reported that about one-third of patients with depression may encounter TRD in their lives. , Thus, the discovery of new therapeutics is required to overturn these unmet medical needs. Recent studies highlighted the importance of gut microbiota in the development of mental disorders, including depression. − Administration of several gut microbiota-modifying interventions like probiotics, such as Lactobacillus reuteri NK33, Lactobacillus paracasei PS23, Lactobacillus plantarum MTCC 9510 , Lactobacillus kefiranofaciens ZW3, Lactobacillus gasseri CP2305, Bifidobacterium breve UBBr-01, and Bifidobacterium infantis UBBI-01, and prebiotics, such as polyphenols, polysaccharides, and dietary fibers, exerted robust antidepressant-like phenotypes in animals by promoting the colonization of other beneficial microorganisms in the host. − However, clinical outcomes of probiotics/prebiotics in human studies are still debatable and inconclusive. , …”

Using Microbiome-Based Approaches to Deprogram Chronic Disorders and Extend the Healthspan following Adverse Childhood Experiences

“…Table 8 [158][159][160][161][162][163] illustrates examples of the relationship between inflammation, oxidative damage and telomere length. It should be noted that efforts to minimize the symptoms of NCDs rather than correcting underlying systems biology defects (e.g., unresolving tissue inflammation) have two very negative outcomes.…”

“…Linking telomere length, inflammation, and gut dysbiosis. [158] Oxidative stress damages telomeres and mitochondria. [159] Early life factors program both inflammation and telomere shortening.…”

Using Microbiome-Based Approaches to Deprogram Chronic Disorders and Extend the Healthspan Following Adverse Childhood Experiences

“…Symptom-only management should be viewed at best as a transient goal when compared to disease-free, life-extending therapeutic outcomes. Linking telomere length, inflammation and gut dysbiosis [158] Oxidative stress damages telomeres and mitochondria [159] Early life factors program both inflammation and telomere shortening [160] Chronic inflammation generates immune aging and cross talk with the telomere complex [161] Link between telomere shortening and tissue inflammation [162] Proposal that inflammation, telomere length, and microbiota may form a loop.…”