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Boyajian et al. Microbiome Res Rep 2024;3:29  https://dx.doi.org/10.20517/mrr.2024.05  Page 19 of 35

               Table 4. Pre-clinical and clinical evidence of prebiotics for the treatment of obesity or aging
                             Disease of
                Agent                  Model investigated  Key findings                     Ref.
                             interest
                                                                                                   [180]
                Galacto-     Obesity   HFD-induced obese male ↓ Weight gain and WAT dysfunction, serum total   Kong et al.
                oligosaccharides       Sprague Dawley rats  cholesterol, triglycerides, HDL-C and LDL-C
                                                                                                      [181]
                             Obesity   Obese men and women   ↑ Bifidobacteria               Krumbeck et al.
                                       (aged 18-65)
                             Obesity   Obese prediabetic men   ↑ Bifidobacterium species    Canfora et al. [166]
                                       and women (aged 45-70)
                             Aging     Aged female C57BL/6J   ↑ Bacteroides, Akkermansia, Lactobacillus, α-diversity;   Arnold et al. [167]
                                       SPF mice         ↓ Clostridium, intestinal permeability, colonic TNF-α
                                                        expression;
                                                        No impact on Bifidobacteria
                                                                                                  [169]
                Marine agar   Aging    Male Drosophila   ↑ Proteobacteria, lifespan, antioxidant activity,   Ma et al.
                oligosaccharide        melanogaster     upregulated IMD gene expression;
                                                        ↓ Firmicutes
                                                                                                  [171]
                Quercetin    Obesity   HFD-induced obese male  ↓ Body weight gain, total cholesterol, triglycerides, free   Jung et al.
                                       C57BL/6J SPF mice  cholesterol, total lipids, lipogenic gene expression
                                                                                                   [175]
                             Abdominal   MSG-induced obese male  ↑ Bacteroidetes, lipid oxidation, locomotor activity, Muc2,  Zhao et al.
                             obesity   C57BL/6J mice    ZO-1
                                                        ↓ Firmicutes, body weight gain, inguinal and epididymal
                                                        fat mass and adipocyte size, lipid deposition
                Dasatinib +   Aging    Aged female BALB/c   ↑ Verrucomicrobia (i.e., Akkermansia), Gram-positive taxa  Saccon et al. [173]
                quercetin              mice             ↓ Firmicutes, intestinal senescence and inflammatory
                                                        gene expression
                                                                                                 [29]
                Aged garlic extract  Obesity  Obese men and women   ↑ Circulating γδ-T cells   Xu et al.
                                       (aged 25-65)     ↓ Serum IL-6 and TNF-α
                Epigallocatechin   Obesity  HFD-induced obese male  ↑ Lifespan              Yuan et al. [177]
                gallate                SPF Wistar rats  ↓ Body weight, serum free fatty acid, disease pathology,
                                                        frailty, serum glucose, insulin, total cholesterol,
                                                        triglycerides, LDL-C, IL-6, TNF- α, ROS
                                                                                                    [178]
                             Obesity   Overweight and obese   ↑ Leptin                      Huang et al.
                                       women (aged 18-65)  ↓ LDL-C
                                                        No impact on body weight, total cholesterol, triglycerides
                                                        or HDL-C
               HFD: High-fat diet; WAT: white adipose tissue; HDL-C: high-density lipoprotein cholesterol; LDL-C: low-density lipoprotein cholesterol; SPF:
               specific pathogen-free; TNF-α: tumor necrosis factor-alpha; IMD: immune deficiency; MSG: monosodium glutamate; muc2: mucin 2; ZO-1: zonula
               occluden-1; γδ-T: gamma delta T; IL-6: interleukin-6; ROS: reactive oxygen species.

               reduced serum total cholesterol, LDL-cholesterol and triglyceride levels, compared to controls. Kimchi-
               derived L. plantarum Ln4 is another strain that reduces weight gain in HFD-fed mice, improves metabolic
               markers (e.g., reduces total triglycerides and insulin resistance, improves glucose tolerance), and decreases
                                                                                      [189]
               inflammatory adipokines (e.g., CRP, MCP-1) in WAT through immunomodulation . The parent strain of
               L. plantarum NCIMB 8826, known as L. plantarum WCFS1, protects age-associated mucosal barrier decline
                                                 [190]
               in mice subjected to accelerated aging . Another subspecies of L. plantarum, TWK10, demonstrates
               beneficial microbial modulatory properties by increasing SCFA-producing species in mice after its
               supplementation . Moreover, age-associated loss of muscle strength, bone mass and cognitive decline was
                             [191]
               prevented in mice treated with L. plantarum TWK10. L. acidophilus has also been studied for its impact on
               obesity in HFD-fed mice . Findings reveal that L. acidophilus reduces body weight and fat mass, activates
                                    [192]
               BAT, and improves metabolic activity (e.g., energy, glucose and lipid metabolism). Obesity-induced
               inflammation (e.g., TNF-α, IL-1β and IFN-γ), as well as TLR4 protein expression and endotoxemia status,
               was also reduced after 12-week supplementation with L. acidophilus through NF-κB inhibition.
               Supplementation with L. acidophilus successfully resolved obesity-induced gut dysbiosis in the mice by
               increasing the F/B ratio and decreasing the abundance of Faecalibaculum and Bifidobacterium, for example.
               Previous literature has discussed the beneficial modulation of the gut microbiota in obese models in more
                    [193]
               detail .
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