This review aims to argue how using probiotics can improve anxiety and depressive behaviour without adverse effects, also exploring the impact of postbiotics on it. Specifically, probiotics have drawn more attention as effective alternative treatments, considering the rising cost of antidepressant and anti-anxiety drugs and the high risk of side effects. Depression and anxiety disorders are among the most common mental illnesses in the world's population, characterised by low mood, poor general interest, and cognitive or motor dysfunction. Thus, this study analysed published literature on anxiety, depression, and probiotic supplementation from PubMed and Scopus, focusing on the last twenty years. This study focused on the effect of probiotics on mental health as they have drawn more attention because of their extensive clinical applications and positive impact on various diseases. Numerous studies have demonstrated how the gut microbiota might be critical for mood regulation and how probiotics can affect host health by regulating the gut-brain axis. By comparing the different works analysed, it was possible to identify a strategy by which they are selected and employed and, at the same time, to assess how the effect of probiotics can be optimised using postbiotics, an innovation to improve mental well-being in humans.

Background: In recent decades, hyaluronic acid (HA) has attracted great attention as a new treatment option for osteoarthritis. Classical therapies are not able to stop the cartilage degeneration process nor do they favor tissue repair. Nowadays, it is accepted that high molecular weight HA can reduce inflammation by promoting tissue regeneration; therefore, the aim of this study was to verify the efficacy of a new high molecular weight HA of plant origin (called GreenIuronic^®) in maintaining joint homeostasis and preventing the harmful processes of osteoarthritis. Methods: The bioavailability of GreenIuronic^® was investigated in a 3D intestinal barrier model that mimics human oral intake while excluding damage to the intestinal barrier. Furthermore, the chemical significance and biological properties of GreenIuronic^® were investigated in conditions that simulate osteoarthritis. Results: Our data demonstrated that GreenIuronic^® crosses the intestinal barrier without side effects as it has a chemical–biological profile, which could be responsible for many specific chondrocyte functions. Furthermore, in the osteoarthritis model, GreenIuronic^® can modulate the molecular mechanism responsible for preventing and restoring the degradation of cartilage. Conclusion: According to our results, this new form of HA appears to be well absorbed and distributed to chondrocytes, preserving their biological activities. Therefore, the oral administration of GreenIuronic^® in humans can be considered a valid strategy to obtain beneficial therapeutic effects during osteoarthritis.

Neuropathic pain is a typical patient disorder resulting from damage and dysfunction of the peripheral neuraxis. Injury to peripheral nerves in the upper extremities can result in a lifelong reduction in quality of life and a devastating loss of sensory and motor function. Since some standard pharmaceutical therapies can cause dependence or intolerance, nonpharmacological treatments have gained great interest in recent years. In this context, the beneficial effects of a new combination of palmitoylethanolamide and Equisetum arvense L. are evaluated in the present study. The bioavailability of the combination was initially analyzed in a 3D intestinal barrier simulating oral intake to analyze its absorption/biodistribution and exclude cytotoxicity. In a further step, a 3D nerve tissue model was performed to study the biological effects of the combination during the key mechanisms leading to peripheral neuropathy. Our results demonstrate that the combination successfully crossed the intestinal barrier and reached the target site, modulating the nerve recovery mechanism after Schwann cell injury and offering the initial response of relieving pain. This work supported the efficacy of palmitoylethanolamide and Equisetum arvense L. in reducing neuropathy and modifying the major pain mechanisms, outlining a possible alternative nutraceutical approach.

Vitamin D plays an important role in numerous cellular functions due to the ability to bind the Vitamin D receptor (VDR), which is present in different tissues. Several human diseases depend on low vitamin D3 (human isoform) serum level, and supplementation is necessary. However, vitamin D3 has poor bioavailability, and several strategies are tested to increase its absorption. In this work, the complexation of vitamin D3 in Cyclodextrin-based nanosponge (CD-NS, in particular, βNS-CDI 1:4) was carried out to study the possible enhancement of bioactivity. The βNS-CDI 1:4 was synthesized by mechanochemistry, and the complex was confirmed using FTIR-ATR and TGA. TGA demonstrated higher thermostability of the complexed form. Subsequently, in vitro experiments were performed to evaluate the biological activity of Vitamin D3 complexed in the nanosponges on intestinal cells and assess its bioavailability without cytotoxic effect. The Vitamin D3 complexes enhance cellular activity at the intestinal level and improve its bioavailability. In conclusion, this study demonstrates for the first time the ability of CD-NS complexes to improve the chemical and biological function of Vitamin D3.

Despite the identification of several innovative targets for avoiding cognitive decline, there has yet to be a widely accepted approach that deals with minimising the deterioration of cognitive function. In this light, recent studies suggest that regulating the gut-brain axis with probiotics is a potential therapeutic strategy to support brain health. For this reason, in vitro models were used to examine the efficacy of different probiotic combinations to enhance intestinal homeostasis and positively affect the brain. Therefore, the new formulation has been evaluated for its capacity to modify intestinal barrier functions in a 3D in vitro model without any adverse effects and directly impact the mechanisms underlying cognitive function in a gut-brain axis model. According to our findings, B. bifidum novaBBF7 10 mg/mL, B. longum novaBLG2 5 mg/mL and L. paracasei TJB8 10 mg/mL may successfully modify the intestinal barrier and improve SCFA production. Successively, the probiotics studied caused no harm at the neuronal level, as demonstrated by iNOS, mitochondrial potential, and cell viability tests, confirming their safety features and enhancing antioxidant mechanisms and antineuroinflammation activity. Additionally, the damage caused by oxidative stress was also healed, and critical pathways that result in cognitive impairment were changed by synergetic action, supporting the hypothesis that brain ageing and neurodegeneration are slowed down. All these findings demonstrate the ability of probiotics to affect cognitive processes and their ability to sustain the mechanisms underlying cognitive function by acting on intestinal function.

The gut–brain axis is a bidirectional relationship between the microbiota and the brain; genes related to the brain and gut synaptic formation are similar. Research on the causal effects of gut microbiota on human behavior, brain development, and function, as well as the underlying molecular processes, has emerged in recent decades. Probiotics have been shown in several trials to help reduce anxiety and depressive symptoms. Because of this, probiotic combinations have been tested in in vitro models to see whether they might modulate the gut and alleviate depression and anxiety. Therefore, we sought to determine whether a novel formulation might affect the pathways controlling anxiety and depression states and alter gut barrier activities in a 3D model without having harmful side effects. Our findings indicate that B. bifidum novaBBF7 10 mg/mL, B. longum novaBLG2 5 mg/mL, and L. paracasei TJB8 10 mg/mL may influence the intestinal barrier and enhance the synthesis of short-chain fatty acids. Additionally, the probiotics studied did not cause neuronal damage and, in combination, exert a protective effect against the condition of anxiety and depression triggered by L-Glutamate. All these findings show that probiotics can affect gut function to alter the pathways underlying anxiety and depression.