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Boyajian et al. Microbiome Res Rep 2024;3:29 https://dx.doi.org/10.20517/mrr.2024.05 Page 25 of 35

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increasing energy expenditure, respectively . Additionally, many lactic acid bacteria produce
antimicrobial peptides (AMPs; e.g., bacteriocins) that are able to avert pathogenic bacteria associated with
obesity and aging [241,242] . Moreover, bacterial-derived exopolysaccharides (EPS) have gained interest as
[244]
[243]
prebiotics and demonstrated anti-obesogenic effects , likely via intestinal microbiota modulation . EPS
from L. acidophilus, L. gasseri, L. plantarum, and L. rhamnosus show significant health-promoting benefits,
including antioxidant properties in an aging mouse model and antitumor activity . Overall, there are
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numerous postbiotics that can be studied and leveraged as novel therapeutics based on their action.
Currently, available evidence suggests that many postbiotics have great promise as therapeutics for obesity
and aging, warranting additional exploration.

Limitations of biotic therapeutics and their investigation
Although hopeful, the use of the microbiome, probiotics, synbiotics, and other biotic forms as next-
generation therapeutics faces many obstacles. Our diverse ecosystem is home to a near-infinite number of
microbes and natural polyphenols with potential prebiotic activity, although not yet discovered. This
provides a great opportunity but also necessitates procedures for researching such materials. For pre- and
probiotics already identified and studied, guidelines on therapeutic dosages are lacking. Similarly,
determining how best to combine different probiotics and create synbiotic formulations for maximal
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synergy remains unknown . The lack of consensus may be partly attributed to the various research
methods used to study biotics, as well as the wide range of agents studied. Biotic-focused studies can be
improved for future studies. For example, quercetin alone may be investigated as an aging therapy without
the addition of Dasatinib. Importantly, pre-clinical and clinical trials of biotics should standardize the
analysis of the gut microbiota as a study outcome. This can also be extended to observational studies on
obese and aged populations to help reach a consensus on gut microbiota alterations associated with these
diseases. Methods for the collection and analysis of microbiota samples must also be standardized. Many
animal studies isolate microbiota from intestinal tissue samples, while clinical trials rely on fecal samples.
These differences may contribute to the high variability seen in the published data on gut microbial
composition. Moreover, many of the recent clinical trials for obesity and aging were conducted in Asia,
which may not be applicable to the Western populations, given the different gut microbiota among these
regions. In addition, variability in diet and exercise can impact results from clinical trials that investigate
biotic therapies. The diagnostic criteria for overweight or obese also vary between studies, as does the
criteria for an elderly age. Standardization of such factors would provide more widely applicable data.
Moreover, to our knowledge, there are no clinical trials on the sarcopenic obese population. The shortage of
clinical studies is a leading limitation for the translation of biotic therapies. The majority of the reviewed
clinical trials had a treatment duration of three months, which does not reflect the safety of biotic therapies.
Long-term investigation of biotic supplementation is therefore warranted. In addition, the investigation of
biotics with therapeutic effects for obesity should be considered as a treatment for aging studies, and vice
versa. Such studies would advance understanding of the link between obesity and aging and may discover
biotics that can be used for both diseases. Overall, additional short- and long-term human trials
investigating different biotics for general health and disease states, such as obesity, unhealthy aging, and
sarcopenic obesity, are required to demonstrate the clinical efficacy of the various biotic forms.

CONCLUSION
The abundance of microorganisms that inhabit the human body and their critical roles in human health and
disease present unlimited potential for microbiome-engineered therapeutics. Obesity and aging are complex
diseases that are together rising in prevalence, increasing the global risk of debilitating and chronic illnesses.
Many hallmarks are shared between obesity and aging, one of which is gut microbial dysbiosis. The gut
microbiota may be targeted to re-establish a healthy flora in obese or aged individuals, thereby improving
the disease phenotypes, underlying metabolic dysfunction and systemic comorbidities. Importantly, the