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Boyajian et al. Microbiome Res Rep 2024;3:29 https://dx.doi.org/10.20517/mrr.2024.05 Page 13 of 35

Figure 2. Schematic representation of the inflammatory pathway from the gut to adipose tissue and the resulting consequences on
human health. LPS: Lipopolysaccharide; LBP: lipopolysaccharide binding protein; CD14: cluster of differentiation 14; NF-κB: nuclear factor
kappa B.

protein (e.g., occludin), and an increase in cecum and serum levels of LPS were found in the mice. Further
investigation of vagal activity in metabolically compromised models is warranted to determine its role in
obesity and related diseases.

The vagus nerve is also proposed to play a role in aging. Dystrophic remodeling of vagal afferents in the GI
may occur with age, leading to decreased vagal stimulation . Moreover, the vagus nerve may be involved
[112]
in the development of neurodegenerative diseases, such as Parkinson’s Disease (PD), through the
misfolding of α-synuclein, a protein that leads to the formation of Lewy bodies that are present in neurons
in PD individuals . In AD patients, a dysbiotic gut and associated intestinal barrier disruption can induce
[113]
neuroinflammation and aggravate amyloid β (Aβ) plaque formation, a known biomarker of AD.
Considering the similarity between α-synuclein and Aβ pathologies, the vagus nerve has been speculated to
play a role in AD similar to that of PD [113,114] . Thus, the link between obesity and aging may be explained, in
part, by the GBA through altered vagal signaling and associated inflammation. However, additional studies
are needed to clarify the role of the vagus nerve in obesity, aging, and the GBA.

CURRENT STRATEGIES FOR TREATING OBESITY AND AGING
Lifestyle modifications
Weight loss is achieved when an energy deficit occurs . Energy expenditure can be increased through
[115]
physical activity, while dieting may reduce energy intake. Thus, the first line of therapy for obesity regards
lifestyle modifications to promote exercise and healthy dietary habits. Expert guidelines recommend an
initial prescription of moderate aerobic activity of at least 150 min per week. Combining exercise with
reduced caloric results in an additional 1% to 3% of body weight, with intensity of physical activity positively
correlated with reduced body fat and maintained muscle mass . Restricting calories through nutritionally
[116]
balanced low-energy diets (800-1,800 kcal/day) or very low-energy diets (less than 800 kcal/day) are
commonly prescribed for weight loss . Low-calorie diets with different macronutrient profiles have
[117]
demonstrated successful treatment of obesity, including ketogenic and Mediterranean diets [118,119] . High-
protein calorie restriction diets may also be effective in reducing weight and beneficially modulating the gut