Probiotic fermentation of plant-based materials can lead to the generation of various bioactive substances via bacterial metabolites and the biotransformation of phenolic compounds. We compared the metabolic differences between fermentation by Limosilactobacillus fermentum KCTC15072BP (LFG) and fermentation by Lactiplantibacillus plantarum KGMB00831 (LPG) in guava leaf extract (0%, 0.5%, and 2% (w/v))-supplemented medium via non-targeted metabolite profiling. By performing multivariate statistical analysis and comparing the different guava leaf extract groups, 21 guava-derived and 30 bacterial metabolites were identified. The contents of guava-derived glucogallin, gallic acid, and sugar alcohols were significantly higher in LFG than they were in LPG. Similarly, significantly higher contents of guava-derived pyrogallol, vanillic acid, naringenin, phloretin, and aromatic amino acid catabolites were obtained with LPG than with LFG. LFG led to significantly higher antioxidant activities than LPG, while LPG led to significantly higher antiglycation activity than LFG. Interestingly, the fermentation-induced increase in the guava-leaf-extract-supplemented group was significantly higher than that in the control group. Thus, the increased bioactivity induced by guava fermentation with the Lactobacillaceae strain may be influenced by the synergistic effects between microbial metabolites and plant-derived compounds. Overall, examining the metabolic changes in plant-based food fermentation by differentiating the origin of metabolites provides a better understanding of food fermentation.

Skeletal muscle atrophy is one of the serious complications of diabetes, which increases the risk of frailty, falls, and mortality. However, interventions for muscle atrophy are limited, and research is needed regarding the treatment of muscle wasting. Recently, the bioconversion of natural products by lactic acid bacteria has been highlighted as a possibility to improve the bioavailability of active ingredients. This process also produces metabolites, which are key signaling mediators for a variety of physiological functions. This study investigated the effect of bioconverted guava leaf (Psidium guajava L., GL) by Lactobacillus plantarum on hyperglycemia-induced skeletal muscle atrophy in type 2 diabetes mellites (T2DM) mice. Diabetes was induced by a high-fat diet with a two-time streptozotocin (STZ) injection (60 mg/kg BW) in male C57BL/6J mice. After diabetes was induced (a fasting blood glucose level (FBG) ≥ 300 mg/dL), the mice were administered with GL (100 mg/kg/day) or bioconverted GL (FGL) (50 mg/kg/day) by oral gavage for 14 weeks. FGL contains different substances such as hydroxyl-isocaproic acid and hydroxyl-isovaleric acid compared to GLE itself, which have potential to prevent muscle degradation in T2DM mice. GL and FGL supplementation reduced the FBG level in T2DM mice. In addition, GL and FGL supplementation enhanced muscle strength, the skeletal muscle cross-sectional area, and ameliorated ubiquitin–proteasome system (UPS)-related pathways in T2DM mice. On the other hand, GLE supplementation ameliorated glucose tolerance demonstrated by oral glucose tolerance test and enhanced insulin signaling pathway. In addition, only FGL supplementation attenuated skeletal muscle inflammation and apoptosis with an improved mammalian target of the rapamycin (mTOR)-autophagy-related pathway. Although administered at a half dose of GLE, FGL demonstrated greater efficacy in regulating the expression of these molecular markers. The result suggests that even GL itself has anti-diabetic effects, and the functionality would be enhanced by the bioconversion of GL with L. Plantarum, which has an additive or/and a synergistic effect. Taken together, FGL could be used as a potential nutraceutical to attenuate muscle degradation by the inhibition of inflammation, the UPS, and the apoptosis pathway.