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Page 2 of 35 Boyajian et al. Microbiome Res Rep 2024;3:29 https://dx.doi.org/10.20517/mrr.2024.05

therapeutic strategies for obese, aged and comorbid (e.g., sarcopenic obese) patient populations. This review
discusses the interrelationship between obesity and aging, with a particular emphasis on the gut microbiome, and
presents biotics as novel therapeutic agents for obesity, aging and related disease states.

Keywords: Microbiome, obesity, aging, gut-brain axis, prebiotics, probiotics, postbiotics, therapeutics

INTRODUCTION
Obesity is a complex, multifactorial and chronic disease that currently affects over 1 billion adults,
adolescents, and children worldwide. As the prevalence of overweight or obese adults continues to rise,
there is a parallel increase observed within the aging population . Aging is the leading risk factor for major
[1]
debilitating and life-threatening diseases. Obesity and aging share many biological hallmarks, including
systemic inflammation and oxidative stress, increased adiposity, skeletal muscle dysfunction, and changes in
[1]
microbiota compositions . In fact, obese individuals are considered prematurely aged individuals,
contributing to the phenomenon of sarcopenic obesity. Moreover, obesity is directly associated with a
reduced life expectancy due to its various metabolic comorbidities. The literature on obesity and aging is
well-versed, but discussion on their relationship and its underlying mechanisms is lacking. This review
intends to examine the link between obesity and aging, highlighting the role of the gut microbiome
[Figure 1]. Briefly, obesity and aging will be introduced, as well as their unique association and shared
features. The role of the gut microbiota in obesity and aging will be discussed with associated evidence of
microbial dysbiosis. A potential pathway from gut dysbiosis to adipose tissue dysfunction will be presented,
exploring it as a possible underlying mechanism for obesity and aging. In addition, the bidirectional
communication system between the enteric and central nervous systems, known as the gut-brain axis
(GBA), will be emphasized as a potential mediator between obesity and longevity. This review also aims to
present the GBA as a novel therapeutic target for obesity and aging. Specifically, the microbiome, probiotics,
synbiotics and other biotic therapies may be used to beneficially modulate the gut microbiota composition,
improve GI functions, and regulate GBA signaling. Biotic-based therapies will be discussed as alternatives to
currently approved anti-obesity and longevity-promoting pharmacotherapies. Future perspectives on biotics
as next-generation therapeutics are offered, warranting additional research. Overall, targeting the gut with
microbiome-engineered therapeutics is a promising strategy for the treatment and/or management of
obesity, longevity, and other chronic diseases. Recent findings will be discussed.

THE GLOBAL BURDEN OF OBESITY: A CHRONIC, MULTIFACTORIAL DISEASE
The worldwide prevalence of obesity has tripled since 1975 and is continuing to advance . The influence of
[2]
the Western diet and sedentary lifestyle throughout the world have led obesity to become a global epidemic
and economic burden. According to the World Health Organization (WHO) 2016 global estimates, 1.9
billion adults are overweight (body mass index (BMI) ≥ 25) and 650 million are considered obese
[3]
(BMI ≥ 30) . Obesity also affects 340 million adolescents and 39 million children, for a total impact of 1
billion people worldwide. Moreover, the Global Burden of Disease group stated that elevated BMI values
were responsible for four million deaths in 2015 . Obesity is a chronic, relapsing, multifactorial disease
[4]
characterized by an increase in body fat, white adipose tissue (WAT) dysfunction, and abnormal fat mass
physical forces. The systemic consequences of obesity include adverse metabolic, biochemical, and
psychosocial outcomes due to its complex underlying pathophysiology. Notably, obesity is a leading risk
factor for cardiovascular disease among other cardiometabolic risk mediators and comorbidities, including
insulin resistance, glucose intolerance, type 2 diabetes, hypertension, dyslipidemia, and systemic
inflammation . The fundamental cause of obesity or weight gain involves an energy imbalance between
[1]
calories consumed and calories expended. However, given the complexity of the disease, obesity is further