Nerve cell death accounts for various neurodegenerative disorders, in which altered immunity to the integrated central nervous system (CNS) might have destructive consequences. This undesirable immune response often affects the progressive neurodegenerative diseases such as Alzheimer’s disease, Parkinson’s disease, schizophrenia and/or amyotrophic lateral sclerosis (ALS). It has been shown that commensal gut microbiota could influence the brain and/or several machineries of immune function. In other words, neurodegenerative disorders may be connected to the gut–brain–immune correlational system. The engrams in the brain could retain the information of a certain inflammation in the body which might be involved in the pathogenesis of neurodegenerative disorders. Tactics involving the use of probiotics and/or fecal microbiota transplantation (FMT) are now evolving as the most promising and/or valuable for the modification of the gut–brain–immune axis. More deliberation of this concept and the roles of gut microbiota would lead to the development of stupendous treatments for the prevention of, and/or therapeutics for, various intractable diseases including several neurodegenerative disorders.

The tryptophan and kynurenine pathway is well-known to play an important role in nervous, endocrine, and immune systems, as well as in the development of inflammatory diseases. It has been documented that some kynurenine metabolites are considered to have anti-oxidative, anti-inflammatory, and/or neuroprotective properties. Importantly, many of these kynurenine metabolites may possess immune-regulatory properties that could alleviate the inflammation response. The abnormal activation of the tryptophan and kynurenine pathway might be involved in the pathophysiological process of various immune-related diseases, such as inflammatory bowel disease, cardiovascular disease, osteoporosis, and/or polycystic ovary syndrome. Interestingly, kynurenine metabolites may be involved in the brain memory system and/or intricate immunity via the modulation of glial function. In the further deliberation of this concept with engram, the roles of gut microbiota could lead to the development of remarkable treatments for the prevention of and/or the therapeutics for various intractable immune-related diseases.

D-amino acids may play key roles for specific physiological functions in different organs including the brain. Importantly, D-amino acids have been detected in several neurological disorders such as schizophrenia, amyotrophic lateral sclerosis, and age-related disorders, reflecting the disease conditions. Relationships between D-amino acids and neurophysiology may involve the significant contribution of D-Serine or D-Aspartate to the synaptic function, including neurotransmission and synaptic plasticity. Gut-microbiota could play important roles in the brain-function, since bacteria in the gut provide a significant contribution to the host pool of D-amino acids. In addition, the alteration of the composition of the gut microbiota might lead to schizophrenia. Furthermore, D-amino acids are known as a physiologically active substance, constituting useful biomarkers of several brain disorders including schizophrenia. In this review, we wish to provide an outline of the roles of D-amino acids in brain health and neuropsychiatric disorders with a focus on schizophrenia, which may shed light on some of the superior diagnoses and/or treatments of schizophrenia.

Mitophagy/autophagy plays a protective role in various forms of liver damage, by renovating cellular metabolism linking to sustain liver homeostasis. A characterized pathway for mitophagy is the phosphatase and tensin homolog (PTEN)-induced putative kinase 1 (PINK1)/Parkin-dependent signaling pathway. In particular, PINK1-mediated mitophagy could play an indispensable role in improving the metabolic dysfunction-associated fatty liver disease (MAFLD) which could precede to steatohepatitis (NASH), fibrosis, and hepatocellular carcinoma. In addition, the PI3K/AKT/mTOR pathway might regulate the various characteristics of cellular homeostasis including energy metabolism, cell proliferation, and/or cell protection. Therefore, targeting mitophagy with the alteration of PI3K/AKT/mTOR or PINK1/Parkin-dependent signaling to eliminate impaired mitochondria might be an attractive strategy for the treatment of MAFLD. In particular, the efficacy of prebiotics for the treatment of MAFLD has been suggested to be useful via the modulation of the PI3K/AKT/mTOR/AMPK pathway. Additionally, several edible phytochemicals could activate mitophagy for the improvement of mitochondrial damages, which could also be a promising option to treat MAFLD with providing liver protection. Here, the potential therapeutics with several phytochemicals has been discussed for the treatment of MAFLD. Tactics with a viewpoint of prospective probiotics might contribute to the development of therapeutic interventions.

Immune checkpoints have been aggressively investigated for anti-cancer immunotherapy. The power of microbiota on the outcome of this immunotherapy has attracted much attention. For example, intestinal microorganisms play a key role in the effectiveness of programmed cell death 1 (PD1) and cytotoxic T lymphocyte-associated antigen 4 (CTLA4) blockade. Additionally, short-chain fatty acids produced in the gut may modulate anti-CTLA4 and anti-PD1 stimulated immune responses and their anti-tumor efficacy. Enhancing the anti-tumor effects of CTLA4 blockade depends on specific Bacteroides sp. of the gut microbiota, suggesting novel approaches to improve such immunotherapies. However, the molecular mechanism of the immune-potentiation remains largely unknown. Changes in the microbiota are influenced by dietary and environmental factors. Here, we have suggested the molecular mechanism of action regarding the interplay between gut microbiota and the anti-cancer immune system with APRO family proteins, which might contribute to innovative cancer therapy in the future.