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Page 24 of 35 Boyajian et al. Microbiome Res Rep 2024;3:29 https://dx.doi.org/10.20517/mrr.2024.05

[226]
treatment period . A similar treatment was evaluated in a recent mother-infant clinical trial conducted in
2
[227]
Finland . Briefly, overweight and early pregnant women (< 18 gestational weeks; BMI ≥ 25 kg/m ) were
treated with probiotics (Lacticaseibacillus rhamnosus HN001 and Bifidobacterium animalis ssp. Lactis 420;
10
10 CFU/day), with or without the addition of fish oil capsules as a synbiotic, until six months post-partum.
The effects of the probiotic and synbiotic treatments were investigated for their influence on the tendency to
be overweight in the participants’ 24-month-old children. Findings reveal that the administered probiotic or
synbiotic reduced the risk of overweight in their 24-month-old children, while no effect on body fat
percentage was found. This study emphasizes the influence of gestational obesity and dietary intake on
infant health, as well as the safety of probiotics and synbiotics.

Clinical evidence shows that specific synbiotic formulations promote the growth of beneficial gut bacteria
and improve systemic health in obese or aged individuals [224,228] . For example, decreased systemic
inflammation and positive effects on body weight were observed following treatment with a synbiotic (i.e.,
B. lactis and fructo-oligosaccharides) in obese women . Synbiotic treatment may also improve overall GI
[229]
symptoms, as evident in children with IBS, where synbiotic treatment was found to be superior to the
[230]
administration of prebiotics alone . However, as with the other biotic therapies, clinical studies are
significantly lacking. Nevertheless, the potential of prebiotics and synbiotics for obesity and aging is
promising and would benefit from further exploration.

Postbiotics
[231]
Non-viable microorganisms and their byproducts may play a role in the health benefits of probiotics .
Such non-living organisms related to or derived from living organisms have emerged as a new concept,
known as postbiotics. Recently, the International Scientific Association for Probiotics and Prebiotics
(ISAPP) defined postbiotics as a “preparation of inanimate microorganisms and/or their components that
confer health benefits on the host”. The benefits of postbiotics occur via a variety of mechanisms, both
directly and indirectly. One notable form of postbiotics is SCFAs, which enable anti-inflammatory and
antioxidative effects, as discussed previously. The production of SCFAs by microbes is desired for many
indications, including obesity and healthy aging. In particular, butyrate and propionate are able to stimulate
gut hormones and reduce food intake . Supplementation of SCFAs has been shown to promote host
[193]
energy expenditure, which is associated with an upregulation of thermogenic genes, and prevent body
weight gain in HFD-fed mice [164,232] . A recent study also revealed that supplementation with SCFAs (i.e.,
acetate, butyrate and propionate) for two weeks in aged mice reduces inflammaging, oxidative stress, and
[233]
metabolic alteration and improves LPS-induced acute lung injury through the gut-lung axis . These
findings support the crosstalk between the gut and distal organs as a therapeutic target. Several probiotic
strains produce SCFAs and demonstrate beneficial effects on gut barrier function, including the
upregulation of TJ proteins . The benefits of L. fermentum NCIMB 5221 mentioned earlier may be partly
[234]
due to its potent SCFA-producing abilities . Additionally, ferulic acid (FA) is an antioxidant known to
[235]
neutralize free radicals, such as ROS. Certain bacterial cells produce FA through the enzyme ferulic acid
[236]
esterase (FAE), which may be particularly beneficial for obese-related dysbiosis . FA exhibits anti-
obesogenic effects, including reducing body weight and visceral fat accumulation, regulating appetite
hormones, and reducing HFD-induced inflammation . FA is also proposed to promote healthy longevity
[237]
through Sirt1 activation, subsequent autophagy, and induction of antioxidant enzymes, among other aging
hallmarks, such as inflammation and cellular senescence . Additionally, bile salts play a critical role in
[238]
[239]
metabolic homeostasis through the regulation of cholesterol levels and fat metabolism . Disordered BAs
are also associated with aging. Specific intestinal bacteria, such as the aforementioned L. plantarum WCFS1,
produce BSH, which deconjugates bile salts and enables the release of free BAs and amino acids, while
[240]
lowering cholesterol . Other metabolic products of the gut, such as vanillic acid and linoleic acid, have
also been proposed as promising postbiotics for obesity due to reports of inducing thermogenesis and