Introduction: Major depressive disorder is a condition involving microbiota–gut–brain axis dysfunction. Increasing research aims to improve depression through gut microbiota regulation, including interventions such as probiotics, prebiotics, and fecal microbiota transplants. However, most research focuses on exogenous depression induced by chronic stress or drugs, with less attention given to endogenous depression. Additionally, research on gut mycobiota in depression is significantly less than that on gut bacteria.Methods: In the present study, Wistar–Kyoto rats were used as an endogenous depression and treatment-resistant depression model, while Wistar rats served as controls. Differences between the two rat strains in behavior, gut bacteria, gut mycobiota, nervous system, endocrine system, immune system, and gut barrier were evaluated. Additionally, the effects of Lactobacillus helveticus NS8 supplementation were investigated.Results: Wistar–Kyoto rats demonstrated increased depressive-like behaviors in the forced swimming test, reduced sucrose preference in the sucrose preference test, and decreased locomotor activity in the open field test. They also exhibited abnormal gut bacteria and mycobiota, characterized by higher bacterial α-diversity but lower fungal α-diversity, along with increased butyrate, L-tyrosine, and L-phenylalanine biosynthesis from bacteria. Furthermore, these rats showed dysfunction in the microbiota–gut–brain axis, evidenced by a hypo-serotonergic system, hyper-noradrenergic system, defective hypothalamic–pituitary–adrenal axis, compromised gut barrier integrity, heightened serum inflammation, and diminished gut immunity. A 1-month L. helveticus NS8 intervention increased the fecal abundance of L. helveticus; reduced the abundance of Bilophila and Debaryomycetaceae; decreased immobility time but increased climbing time in the forced swimming test; reduced hippocampal corticotropin-releasing hormone levels; decreased hypothalamic norepinephrine levels; increased hippocampal glucocorticoid receptor, brain-derived neurotrophic factor dopamine, and 5-hydroxyindoleacetic acid content; and improved the gut microbiota, serotonergic, and noradrenergic system.Conclusion: The depressive phenotype of Wistar–Kyoto rats is not only attributed to their genetic context but also closely related to their gut microbiota. Abnormal gut microbiota and a dysfunctional microbiota–gut–brain axis play important roles in endogenous depression, just as they do in exogenous depression. Supplementing with probiotics such as L. helveticus NS8 is likely a promising approach to improve endogenous depression and treatment-resistant depression.

Age-related macular degeneration (AMD) is one of the major causes of blindness in elderly populations. However, the dry form of AMD has lack of effective treatments. The fruits of Aronia melanocarpa are rich in anthocyanins. In this study, the protective effects of aronia fruit extract on rat retina were investigated using a NaIO₃-induced dry AMD model. Full-field electroretinograms (ERGs) showed that b-wave amplitudes were significantly decreased and the retina structures were disordered in the model. The extract treatment alleviated the injuries. The b-wave amplitudes increased 61.5% in Scotopic 0.01ERG, 122.0% in Photopic 3.0ERG, and 106.8% in Photopic 3.0 flicker; the retina structure disorder was improved with the thickness of outer nuclear layer increasing by 44.1%; and the malonaldehyde level was significantly reduced in extract-treated rat retinas compared to the model. The proteomics analysis showed the expressions of five crystallin proteins, α-crystallin A chain, β-crystallin B2, β-crystallin A3, α-crystallin B chain, and γ-crystallin S, which protect retina ganglion cells, were increased by 7.38-, 7.74-, 15.30-, 4.86-, and 9.14-fold, respectively, in the extract treatment compared to the control, which was also confirmed by immunoblotting. The results suggest that aronia fruit extract, probably due to its anthocyanins, could protect the rat retina by alleviating oxidative damages and by upregulating the crystallin proteins to protect its nerve system.

Introduction: The highly processed western diet is substituting the low-processed traditional diet in the last decades globally. Increasing research found that a diet with poor quality such as western diet disrupts gut microbiota and increases the susceptibility to various neurological and mental disorders, while a balanced diet regulates gut microbiota and prevents and alleviates the neurological and mental disorders. Yet, there is limited research on the association between the disease burden expanding of neurological and mental disorders with a dietary transition.Methods: We compared the disability-adjusted life-years (DALYs) trend by age for neurological and mental disorders in China, in the United States of America (USA), and across the world from 1990 to 2019, evaluated the dietary transition in the past 60 years, and analyzed the association between the burden trend of the two disorders with the changes in diet composition and food production.Results: We identified an age-related upward pattern in disease burden in China. Compared with the USA and the world, the Chinese neurological and mental disorders DALY percent was least in the generation over 75 but rapidly increased in younger generations and surpassed the USA and/or the world in the last decades. The age-related upward pattern in Chinese disease burdens had not only shown in the presence of cardiovascular diseases, neoplasms, and diabetes mellitus but also appeared in the presence of depressive disorders, Parkinson’s disease, Alzheimer’s disease and other dementias, schizophrenia, headache disorders, anxiety disorders, conduct disorders, autism spectrum disorders, and eating disorders, successively. Additionally, the upward trend was associated with the dramatic dietary transition including a reduction in dietary quality and food production sustainability, during which the younger generation is more affected than the older. Following the increase in total calorie intake, alcohol intake, ratios of animal to vegetal foods, and poultry meat to pulses, the burdens of the above diseases continuously rose. Then, following the rise of the ratios of meat to pulses, eggs to pulses, and pork to pulses, the usage of fertilizers, the farming density of pigs, and the burdens of the above disease except diabetes mellitus were also ever-increasing. Even the usage of pesticides was positively correlated with the burdens of Parkinson’s disease, schizophrenia, cardiovascular diseases, and neoplasms. Contrary to China, the corresponding burdens of the USA trended to reduce with the improvements in diet quality and food production sustainability.Discussion: Our results suggest that improving diet quality and food production sustainability might be a promising way to stop the expanding burdens of neurological and mental disorders.

Editorial: The effect of gut microbiota on the brain structure and function

Introduction: Current clinical practice often assumes that gut microbiome assessment before selecting probiotic species, assuming a ‘test-then-match’ strategy yields better outcomes. However, routine testing has limited predictive value for probiotic efficacy, and many commercial probiotics fail to achieve sustained clinical improvement. Methods: In this Hypothesis and Theory article, we propose a novel, testable hypothesis: prioritize remodelling the gut environment using metabolically potent probiotics, (i.e., strains with high capacity to produce beneficial metabolites such as short-chain fatty acids, bioactive peptides, and organic acids) without prior microbiome assessment—a ‘condition-then-attract’ strategy. Our hypothesis is motivated by preclinical studies demonstrating the metabolic potency of specific strains of Lactobacillus helveticus and Lactobacillus fermentum (e.g., NS8 and NS9 originally isolated from Mongolian fermented koumiss). Results: We derive several directly testable predictions from this framework, including that a randomized controlled trial comparing ‘test-then-match’ versus ‘condition-then-attract’ strategies would show that prior gut assessment does not improve outcomes, and that metabolically potent probiotics will outperform less active strains regardless of species identity. Discussion: We contend that refocusing from species-level matching to strain-level metabolic potency may offer a more effective and simpler alternative. Future research should prioritize metabolic potency over colony-forming unit counts and reconsider the necessity of routine pre-intervention gut assessment. Our framework does not rely on a single metabolite but embraces diverse mechanisms—proteolysis, carbohydrate fermentation, pH modulation—that collectively restore gut homeostasis.