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Page 18 of 35 Boyajian et al. Microbiome Res Rep 2024;3:29 https://dx.doi.org/10.20517/mrr.2024.05

Overall, the use of prebiotics as therapeutic interventions is gaining popularity. Clinical trials have
investigated components that are found in the everyday diet. For example, Xu et al. investigated the effects
[29]
of aged garlic extract consumption in adults with obesity for six weeks , but gut microbiota composition
was not analyzed. Serum inflammatory markers (e.g., IL-6, TNF-α) were significantly reduced in the treated
participants, compared to those given placebo capsules, while circulating immune cells (e.g., γδ-T cells)
increased, inferring fewer immune cells were present in adipose tissue. However, levels of CRP and
adipokines (i.e., leptin and adiponectin) did not change in response to the intervention. Green tea extract,
epigallocatechin gallate (EGCG), has also been studied for anti-inflammatory, anti-obesogenic, and anti-
aging properties. A recent pre-clinical trial found that EGCG extends lifespan in high-fat-fed obese rats,
[177]
while suppressing oxidative stress and activating fatty acid and cholesterol metabolism . In addition,
previous clinical studies have reported that EGCG reduces low-density lipoprotein (LDL) cholesterol and
increases leptin levels in overweight and obese women after six-week supplementation . Similarly,
[178]
ellagitannins are bioactive polyphenols present in certain fruits, nuts, and seeds (e.g., pomegranate) .
[179]
Once ingested, ellagitannins are metabolized by gut bacteria to produce urolithin A, a natural compound
and potential anti-aging agent that promotes mitophagy and mitochondrial function. Although evidence is
growing for the use of prebiotic, natural compounds for obesity and healthy aging, additional research is
needed. Future work may optimize the therapeutic effects of these prebiotics through dosage studies,
methods of delivery (e.g., capsule, powder), and treatment period. Overall, various prebiotics can be used to
improve obesity and aging markers. A summary of the abovementioned findings from pre-clinical studies
and human trials is presented in Table 4.

Probiotics
Probiotics are live microorganisms that elicit health benefits to the host when administered in adequate
amounts . Probiotics have a multitude of health benefits including, but not limited to, producing SCFAs,
[182]
synthesizing vitamins, lowering gut pH, enhancing immune response, and exhibiting antimicrobial activity
against pathogenic species . Most notably, probiotics can modulate the gut microbiota by increasing the
[183]
[184]
abundance of beneficial species when regularly consumed . Probiotics are available in the form of
functional food products (e.g., yogurt, cheese, kefir), as well as dietary supplements. The most widely used
strains of probiotics include those of the Lactobacillus and Bifidobacterium genera. Thus, there is a
multitude of evidence in support of probiotic therapies for obesity and aging.

Lactobacillus and Bifidobacterium strains improve obesity and aging in experimental models
Supplementation with various probiotic strains has been studied for its effects on obesity features. Similarly,
the term “gerobiotics” was recently proposed by Tsai et al. to classify probiotic strains that can attenuate
fundamental mechanisms of aging, reduce the physiological aging process, and extend the health span of the
host . Thus, various Lactobacillus strains have been investigated as obesity and aging therapeutics.
[185]
Lactobacillus fermentum is a well-studied probiotic with evidence of reducing metabolic disease markers,
including insulin resistance, hyperinsulinemia, and hypercholesteremia, in vivo . Other research revealed
[186]
supplementation with L. fermentum NCIMB 5221, as well as a probiotic formulation (B. longum spp.
infantis NCIMB 702255, L. fermentum NCIMB 5221, and Lactobacillus plantarum NCIMB 8826) rescues
weight gain in high-fat-fed, diet-induced obese Drosophila . The individual probiotics also had positive
[187]
impacts on total weight, glucose and triglyceride levels. These effects were closely mimicked in diet-induced
diabetic Drosophila in the same study, inferring the potential of these probiotics and their combination to
simultaneously treat multiple metabolic disorders with shared pathophysiology. A microencapsulated
probiotic blend (L. rhamnosus NCIMB 6375, L. plantarum NCIMB 8826 and L. fermentum NCIMB 5221)
was also studied for its effects on HFD-induced MetS hamsters and resulted in favorable alterations to the
gut microbiota through decreasing the F/B ratio . Although there was no impact on high-density
[188]
lipoprotein (HDL) cholesterol, the probiotic-treated group showed improved metabolic regulation via