L-rhamnose (6-deoxy-mannose) occurs in nature mainly as a component of certain plant structural polysaccharides and bioactive metabolites but has also been found in some microorganisms and animals. The release of l-rhamnose from these substrates is catalysed by extracellular enzymes including α-l-rhamnosidases, the production of which is induced in its presence. The free sugar enters cells via specific uptake systems where it can be metabolized. Of two l-rhamnose catabolic pathways currently known in microorganisms a non-phosphorylated pathway has been identified in fungi and some bacteria but little is known of the regulatory mechanisms governing it in fungi. In this study two genes (lraA and lraB) are predicted to be involved in the catabolism of l-rhamnose, along with lraC, in the filamentous fungus Aspergillus nidulans. Transcription of all three is co-regulated with that of the genes encoding α-l-rhamnosidases, i.e. induction mediated by the l-rhamnose-responsive transcription factor RhaR and repression of induction in the presence of glucose via a CreA-independent mechanism. The participation of lraA/AN4186 (encoding l-rhamnose dehydrogenase) in l-rhamnose catabolism was revealed by the phenotypes of knock-out mutants and their complemented strains. lraA deletion negatively affects both growth on l-rhamnose and the synthesis of α-l-rhamnosidases, indicating not only the indispensability of this pathway for l-rhamnose utilization but also that a metabolite derived from this sugar is the true physiological inducer.

Canine osteoarthritis is a progressive degenerative joint condition characterized by inflammation, structural damage, pain, and impaired joint function. Osteoarthritis risk is influenced not only by well-established factors such as age, genetics, obesity and underlying arthropathies, but also by systemic conditions such as low-grade inflammation and sarcopenia. Current interventions are primarily focused on pain relief rather than mitigating physiological impairment, despite recent veterinary guidelines. In this study, several preclinical models were employed to identify postbiotic candidates with potential to promote canine joint health. An initial screening of nine heat-treated bacterial strains identified two Lacticaseibacillus rhamnosus strains, PRIOME^® JH and HT-PB01, which demonstrated significant anti-inflammatory activity on canine chondrocytes. Further characterization revealed that these two strains significantly increased type II collagen synthesis in canine chondrocytes and modulate immune responses in canine macrophages, enhancing Interleukin-10 secretion over Interleukin-12. Additionally, both strains showed potential in mitigating risk factors such as gut inflammation and permeability, fat accumulation and sarcopenia in Caenorhabditis elegans models. In conclusion, this study identified two promising postbiotic candidates, PRIOME^® JH and HT-PB01, with the potential to target key risk factors associated with osteoarthritis through multifactorial mechanisms. These findings emphasize conducting dog clinical trials to evaluate their relevance in osteoarthritis.

In a previous clinical trial, it was shown that a probiotic blend (Bifidobacterium longum CECT 7347 (Esflorin1™), Lacticaseibacillus rhamnosus CECT 8361 (BPL15) and Lacticaseibacillus casei CECT 9104 (BPL4)) reduced oxidative stress in males engaging in intense exercise. The present study evaluated whether the probiotic blend’s functional properties are preserved after heat treatment and investigated the underlying mechanism of action using preclinical models. The antioxidant, immunomodulatory and intestinal effects of the heat-treated and probiotic blends were assed using in vitro assays and Caenorhabditis elegans (C. elegans) models. The heat-treated blend preserved the antioxidant activity by scavenging free radicals, reducing intracellular reactive oxygen species and enhancing survival in C. elegans under oxidative stress, possibly via sod-3 upregulation in the CF1553 strain. It also enhanced mitochondrial biogenesis and ATP production in C2C12 via AMPK phosphorylation. Both versions attenuated a gut inflammatory response, improved intestinal barrier in Caco-2 cells and C. elegans and exhibited immunomodulatory activity in U937 macrophages at the tested concentrations. These findings support the heat-treated blend as a promising postbiotic supplement to manage oxidative stress and other physiological alterations associated with intense exercise.