Modulation of gut microbiota and delayed immunosenescence as a result of syringaresinol consumption in middle-aged mice

Abstract

Age-associated immunological dysfunction (immunosenescence) is closely linked to perturbation of the gut microbiota. Here, we investigated whether syringaresinol (SYR), a polyphenolic lignan, modulates immune aging and the gut microbiota associated with this effect in middle-aged mice. Compared with age-matched control mice, SYR treatment delayed immunosenescence by enhancing the numbers of total CD3+ T cells and naïve T cells. SYR treatment induced the expression of Bim as well as activation of FOXO3 in Foxp3+ regulatory T cells (Tregs). Furthermore, SYR treatment significantly enhanced the Firmicutes/Bacteroidetes ratio compared with that in age-matched controls by increasing beneficial bacteria, Lactobacillus and Bifidobacterium, while reducing the opportunistic pathogenic genus, Akkermansia. In addition, SYR treatment reduced the serum level of lipopolysaccharide-binding protein, an inflammatory marker, and enhanced humoral immunity against influenza vaccination to the level of young control mice. Taken together, these findings suggest that SYR may rejuvenate the immune system through modulation of gut integrity and microbiota diversity as well as composition in middle-aged mice, which may delay the immunosenescence associated with aging.

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“…These modifications of the composition and diversity of gut microbiota were accompanied with an augmentation of naïve T cells, diminution of regulatory T cells and restoration of T cell effector functions in middle-aged mice. Finally, syringaresinol-treated middle-aged mice had better serologic responses to influenza vaccination compared to untreated mice [45]. We and other groups have demonstrated that the microbiota composition could predict clinical response after immune checkpoints treatments in mice [46,47] and in patients with metastatic melanoma [48].…”

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“…Polyphenols have also demonstrated efficacy in attenuating age‐associated inflammation and dysregulation to the gut microbiota of mice. Treatment of middle‐aged mice (40 weeks old) with the polyphenolic lignan syringaresinol reduced circulating levels of the proinflammatory marker LPS binding protein (LBP), while also increasing the humoral response to vaccination with the influenza virus . Moreover, syringaresinol modulated the gut microbiota by increasing the relative abundance of Lactobacillus and Bifidobacterium species, while decreasing levels of the potentially harmful Akkermansia genus .…”

“…Treatment of middle‐aged mice (40 weeks old) with the polyphenolic lignan syringaresinol reduced circulating levels of the proinflammatory marker LPS binding protein (LBP), while also increasing the humoral response to vaccination with the influenza virus . Moreover, syringaresinol modulated the gut microbiota by increasing the relative abundance of Lactobacillus and Bifidobacterium species, while decreasing levels of the potentially harmful Akkermansia genus . While these are promising preclinical studies, such modulators of the microbiota will need to be assessed in humans in order to determine whether they display efficacy in mitigating the deleterious effects of aging in humans.…”

Long-term intake of Lactobacillus paracasei KW3110 prevents age-related chronic inflammation and retinal cell loss in physiologically aged mice

“…Age-related alterations of gut microbiota composition have been reported to cause immune senescence and intestinal chronic inflammation [ 34 , 47 ]. Although some probiotics improve the intestinal environment and suppress inflammation, the effects of long-term ingestion of probiotics remain unclear.…”

“…Thymic involution and disruption of homeostatic T cell proliferation, including decreased numbers of naïve T cells, accumulation of memory T cells, and increased numbers of regulatory T cells (Tregs), have been studied [ 22 – 24 ], and altered numbers of B cells with aging, reduced antibody production, and age-related dysfunction of other innate immune cells have also been reported [ 25 – 30 ]. Although some food materials or constituents, for example, prebiotics and probiotics, can improve age-related immune defects [ 31 – 34 ], their mechanism remains poorly understood. Recent studies suggested that the gut microbiota composition may be associated with age-related immune dysfunctions [ 35 – 37 ].…”