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Ultra-processed food exposure and health outcomes: Current evidence, controversies, and future perspectives.
Ultra-processed food (UPF) exposure has increased markedly worldwide and is now a major contributor to total energy intake in many countries. Evidence from large prospective cohort studies suggests that higher UPF exposure is associated with adverse health outcomes, including overweight and obesity, type 2 diabetes, cardiovascular disease, selected cancers, depression, and increased all-cause mortality. Short-term experimental studies further indicate that diets rich in UPFs can promote excess energy intake and weight gain, supporting biological plausibility. Several mechanisms have been proposed, including poor nutrient quality, high glycemic load, altered food structure and satiety signaling, exposure to additives and contaminants, gut microbiome perturbations, and displacement of minimally processed foods. Nevertheless, the field remains debated. Major controversies concern the Nova classification system, substantial heterogeneity within the UPF category, challenges in reproducible classification, and the extent to which observed associations reflect processing itself rather than nutrient profile, dietary patterns, or broader food environments. These issues hinder causal inference and sustain ongoing debate over whether UPFs act as independent etiological factors or function as markers of unhealthy diets. Policy responses vary internationally, ranging from explicit inclusion of UPFs in dietary guidelines to predominantly nutrient-based or hybrid frameworks. This narrative review summarizes current evidence linking UPF exposure to health outcomes, critically examines methodological and conceptual limitations, and discusses implications for future research and public health policy. See also the graphical abstract(Fig. 1).
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Bulky substrates of isoleucine 2-epimerase: α-Neopentylglycine and NV-5138.
Isoleucine 2-epimerase from Lactobacillus buchneri (LbIleE) catalyzes the pyridoxal 5'-phosphate-dependent, reversible, racemization or epimerization of nonpolar amino acids at the C-2 position. The integral role of the enzyme in the biosynthesis of branched-chain d-amino acids makes it a potential target for the development of antimicrobial agents. Probing the hydrophobic active-site pocket with a series of alkyl boronic acids, we show that the hydrophobic pocket accommodates the neopentyl group with enhanced binding affinity relative to the sec-butyl group. Subsequently, we show that LbIleE catalyzes the racemization of l- and d-α-neopentylglycine, exhibiting binding affinities for these substrates 6- and 24-fold greater than those for l-Ile and d-allo-Ile, but with catalytic efficiencies (kcat/Km) reduced 46- and 27-fold, respectively. NV-5138 is a ligand of the leucine-binding site of Sestrin2, which activates the mechanistic target of rapamycin complex1 (mTORC1) and is structurally similar to α-neopentylglycine. Our demonstration that LbIleE catalyzes the racemization of l-NV-5138 (kcat/Km = 2.2 ± 0.2 s-1 mM-1), along with the fact that L. buchneri can be present in the human gut microbiome, suggests that formation of d-NV-5138 could occur in humans when l-NV-5138 is used as a pharmacological intervention for depression.
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REM sleep behaviour disorder (RBD): Personal perspectives and research priorities.
The formal identification and naming of rapid eye movement (REM) sleep behaviour disorder (RBD) in 1985-1987 is described; the historical background of RBD from 1966 to 1985 is briefly discussed; and RBD milestones are presented. Current knowledge on RBD is identified with reference to recent comprehensive reviews, allowing for a focus on research priorities for RBD: factors and predictors of neurodegenerative phenoconversion from isolated RBD and patient enrolment in neuroprotective trials; isolated RBD clinical research cohorts; epidemiology of RBD; traumatic brain injury, post-traumatic stress disorder, RBD and neurodegeneration; depression, RBD and synucleinopathy; evolution of prodromal RBD to neurodegeneration; gut microbiome dysbiosis and colonic synuclein histopathology in isolated RBD; other alpha-synuclein research in isolated RBD; narcolepsy-RBD; dreams and nightmares in RBD; phasic REM sleep in isolated RBD; RBD, periodic limb movements, periodic limb movement disorder pseudo-RBD; other neurophysiology research in RBD; cardiac scintigraphy (123I-MIBG) in isolated RBD; brain magnetic resonance imaging biomarkers in isolated RBD; microRNAs as biomarkers in isolated RBD; actigraphic, other automated digital monitoring and machine learning research in RBD; prognostic counselling and ethical considerations in isolated RBD; and REM sleep basic science research. RBD research is flourishing, and is strategically situated at an ever-expanding crossroads of clinical (sleep) medicine, neurology, psychiatry and neuroscience.
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The Role of Diet as a Modulator of the Inflammatory Process in the Neurological Diseases.
Neurological diseases are recognized as major causes of disability and mortality worldwide. Due to the dynamic progress of diseases such as Alzheimer's disease (AD), Parkinson's Disease (PD), Schizophrenia, Depression, and Multiple Sclerosis (MD), scientists are mobilized to look for new and more effective methods of interventions. A growing body of evidence suggests that inflammatory processes and an imbalance in the composition and function of the gut microbiome, which play a critical role in the pathogenesis of various neurological diseases and dietary interventions, such as the Mediterranean diet the DASH diet, or the ketogenic diet can have beneficial effects on their course. The aim of this review was to take a closer look at the role of diet and its ingredients in modulating inflammation associated with the development and/or progression of central nervous system diseases. Presented data shows that consuming a diet abundant in fruits, vegetables, nuts, herbs, spices, and legumes that are sources of anti-inflammatory elements such as omega-3 fatty acids, polyphenols, vitamins, essential minerals, and probiotics while avoiding foods that promote inflammation, create a positive brain environment and is associated with a reduced risk of neurological diseases. Personalized nutritional interventions may constitute a non-invasive and effective strategy in combating neurological disorders.
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Global research trends on maternal separation paradigms as an early life stress model: A bibliometric analysis.
BACKGROUND: Maternal separation (MS) is an early life stress model that is often studied to determine how early life stress affects brain development and psychopathological adaptation. As society has developed, public health problems have become increasingly prominent, and this research area has attracted significant attention. However, to date, there has been no systematic bibliometric study on MS. The aim of this study was to analyze the trends and frontiers in MS using bibliometrics and provide a scientific reference to researchers in the field. METHODS: Utilizing VOSviewer, CiteSpace, and Microsoft Excel, examined data obtained from the WoSCC, which encompasses the years 2002-2021. RESULTS: In this bibliometric study, we analyzed 6209 articles related to MS authored by 24,174 researchers across 121 countries and regions and published in 2219 journals. The United States had the most publications (2,232, 35.95%) and both the United States and the United Kingdom had the highest h-index. Institutions in the United States and France had the most published articles and citations. Keyword clustering analysis revealed associations between MS and adverse early life experiences, the hypothalamic-pituitary-adrenal (HPA) axis, stress, gene expression, and depression. CONCLUSIONS: This bibliometric analysis highlights the current research focus on the long-term effects of MS on emotional cognition, the HPA axis, epigenetic changes, and their links to gut microbiome imbalances. Future research may expand on these findings to investigate the underlying mechanisms and broader health and societal implications of MS. These results provide a comprehensive overview of the current research landscape in MS and offer valuable insights for researchers to guide future investigations in this field.
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A Potential Role for Sirtuin-1 in Alzheimer's Disease: Reviewing the Biological and Environmental Evidence.
Sirtuin-1 (Sirt1), encoded by the SIRT1 gene, is a conserved Nicotinamide adenine dinucleotide (NAD+) dependent deacetylase enzyme, considered as the master regulator of metabolism in humans. Sirt1 contributes to a wide range of biological pathways via several mechanisms influenced by lifestyle, such as diet and exercise. The importance of a healthy lifestyle is of relevance to highly prevalent modern chronic diseases, such as Alzheimer's disease (AD). There is growing evidence at multiple levels for a role of Sirt1/SIRT1 in AD pathological mechanisms. As such, this review will explore the relevance of Sirt1 to AD pathological mechanisms, by describing the involvement of Sirt1/SIRT1 in the development of AD pathological hallmarks, through its impact on the metabolism of amyloid-β and degradation of phosphorylated tau. We then explore the involvement of Sirt1/SIRT1 across different AD-relevant biological processes, including cholesterol metabolism, inflammation, circadian rhythm, and gut microbiome, before discussing the interplay between Sirt1 and AD-related lifestyle factors, such as diet, physical activity, and smoking, as well as depression, a common comorbidity. Genome-wide association studies have explored potential associations between SIRT1 and AD, as well as AD risk factors and co-morbidities. We summarize this evidence at the genetic level to highlight links between SIRT1 and AD, particularly associations with AD-related risk factors, such as heart disease. Finally, we review the current literature of potential interactions between SIRT1 genetic variants and lifestyle factors and how this evidence supports the need for further research to determine the relevance of these interactions with respect to AD and dementia.
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Maternal weight, gut microbiota, and the association with early childhood behavior: the PREOBE follow-up study.
BACKGROUND AND AIM: Maternal overweight and breastfeeding seem to have a significant impact on the gut microbiota colonization process, which co-occurs simultaneously with brain development and the establishment of the "microbiota-gut-brain axis", which potentially may affect behavior later in life. This study aimed to examine the influence of maternal overweight, obesity and/or gestational diabetes on the offspring behavior at 3.5 years of age and its association with the gut microbiota already established at 18 months of life. METHODS: 156 children born to overweight (OV, n = 45), obese (OB, n = 40) and normoweight (NW, n = 71) pregnant women participating in the PREOBE study were included in the current analysis. Stool samples were collected at 18 months of life and gut microbiome was obtained by 16S rRNA gene sequencing. Behavioral problems were evaluated at 3.5 years by using the Child Behavior Checklist (CBCL). ANOVA, Chi-Square Test, ANCOVA, Spearman's correlation, logistic regression model and generalized linear model (GLM) were performed. RESULTS: At 3.5 years of age, Children born to OV/OB mothers showed higher scores in behavioral problems than those born to NW mothers. Additionally, offspring born to OB mothers who developed gestational diabetes mellitus (GDM) presented higher scores in attention/deficit hyperactivity and externalizing problems than those born to GDM OV/NW mothers. Fusicatenibacter abundance found at 18 months of age was associated to lower scores in total, internalizing and pervasive developmental problems, while an unidentified genus within Clostridiales and Flavonifractor families abundance showed a positive correlation with anxiety/depression and somatic complaints, respectively. On the other hand, children born to mothers with higher BMI who were breastfed presented elevated anxiety, internalizing problems, externalizing problems and total problems scores; likewise, their gut microbiota composition at 18 months of age showed positive correlation with behavioral problems at 3.5 years: Actinobacteria abundance and somatic complaints and between Fusobacteria abundance and withdrawn behavior and pervasive developmental problems. CONCLUSIONS: Our findings suggests that OV/OB and/or GDM during pregnancy is associated with higher behavioral problems scores in children at 3.5 years old. Additionally, associations between early life gut microbiota composition and later mental health in children was also found.
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Lactobacillus plantarum MH-301 as an effective adjuvant to isotretinoin in the treatment of acne vulgaris: a randomized and open-label trail.
INTRODUCTION: Acne vulgaris is a common chronic inflammatory skin disease originating in the sebaceous gland units of the skin follicles. Isotretinoin is presently the primary choice for the treatment of acne vulgaris. However, it could induce several adverse reactions like diarrhea, cheilitis, headache, elevated triglyceride levels and risk of inflammatory bowel disease and depression. Hence, it is imperative to seek an alternative therapy. METHODS: One hundred five patients were randomly divided into 3 groups, and received a baseline treatment of oral doxycycline for the initial 4 weeks. Group I received isotretinoin oral for 12 weeks; Group P received oral Lactobacillus plantarum MH-301 treatment for 12 weeks; Group IP received combined treatment with oral probiotics and oral isotretinoin for 12 weeks. The number of skin lesions was recorded at 0, 4, 8, and 12 weeks during the treatment to compare the efficacy of each intervention, and skin and fecal samples were collected from patients at 12 weeks for high-throughput sequencing to explore the microbiota differences between various groups. RESULTS: Our results revealed that the combination of L. plantarum MH-301 with isotretinoin significantly reduced the number of skin lesions in patients compared to using L. plantarum MH-301 and isotretinoin alone (p < 0.001). Additionally, skin microbiome High-throughput analysis indicated the restorative effects of L. plantarum MH-301 on skin microbial diversity while also observing a reduction in the main microbiota of skin lesions, Propionibacterium and Corynebacterium. Meanwhile, gut microbiome High-throughput analysis showed that it could regulate disorders of the intestinal microbiota and increased the abundance of probiotics such as Lactobacillus, Bifidobacterium, Coprococcus and Bacteroides genera. CONCLUSION: In conclusion, L. plantarum MH-301 could be used in combination with isotretinoin for optimal results in the treatment of acne vulgaris. The research conducted provides theoretical and data support for the adjuvant effect of L. plantarum in the treatment of acne vulgaris. CLINICAL TRIAL REGISTRATION: [ClinicalTrials.gov], identifier (ChiCTR2200063499).
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Psychobiotic, nutritional, and behavioral interventions targeting the microbiome-gut-brain axis in depression, anxiety, and stress: a scoping review.
Probiotics and psychobiotics are increasingly investigated as microbiome-gut-brain axis (MGBA)-targeted strategies for managing depression, anxiety, and stress-related symptoms, but human evidence remains fragmented across intervention types and biomarker domains. We conducted a scoping review of human intervention studies to map MGBA-targeted psychobiotic, nutritional, dietary, and behavioral interventions, with a specific focus on symptom-biomarker bridging evidence. Searches of major biomedical and multidisciplinary databases combined key terms for the microbiome/gut-brain axis, depression/anxiety/stress, probiotics/psychobiotics, dietary or behavioral interventions, and biomarker domains. The search yielded 1,390 records; 72 full-text reports were assessed; 32 original reports were retained after report-level adjudication; and, after study-family consolidation, 30 independent human studies were included in the study-level synthesis. Studies were classified as direct bridge, parallel evidence, or no bridge according to whether biomarker changes were statistically linked to emotional outcomes. Most included studies focused on probiotic or psychobiotic interventions, with fewer studies examining prebiotics, synbiotics, short-chain fatty acid approaches, dietary interventions, or mind-body/behavioral strategies. Across the 30 studies, 9 were classified as direct bridge, 18 as parallel evidence, and 3 as no bridge. The most frequently examined biomarker domains were gut microbiota, microbial metabolites, and inflammation/immune markers, with common specific readouts including BDNF, 5-HT/serotonin-related markers, IL-6, TNF-α/CRP, cortisol/CAR, and SCFA/metabolite measures. Overall, MGBA-related nutritional and psychobiotic interventions may contribute to mood-symptom management by modulating microbial, metabolic, immune, neuroendocrine, and neurotrophic pathways, but robust symptom-biomarker bridging evidence remains limited. Future trials should predefine bridge hypotheses, standardize core biomarker domains and sampling time points, and clearly distinguish primary trial reports from linked secondary publications.
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Acori Tatarinowii Rhizoma prevents the fluoxetine-induced multiple-drug resistance of Escherichia coli against antibiotics.
BACKGROUND: In treating depression, the residual anti-depressant in gut interacts with the microbiome, leading to the appearance of multiple drug resistant (MDR) mutants, which poses a challenge for the treatment of infectious complications. Strategy is needed to combat this issue. Acori Tatarinowii Rhizoma (ATR, rhizome of Acorus tatarinowii Schott, Araceae), a traditional Chinese medicine, has been widely used for treatment of neurological disorders and gastrointestinal digestive disease in China. Here, ATR was demonstrated an excellent MDR-preventing effect in fluoxetine-induced Escherichia coli (E. coli). AIM OF THE STUDY: This study aimed to reveal the effective role of ATR and its signaling cascades involved in preventing fluoxetine-induced MDR. MATERIALS AND METHODS: The water extract of ATR was co-applied with sub-minimum inhibitory concentration (100 mg/l) of fluoxetine in E. coli to evaluate its anti-MDR potential. Formation of reactive oxygen species (ROS) and expression of MDR-related genes in bacteria were measured by dichloro-dihydro-fluorescein diacetate assay and real-time PCR, respectively. Two fluorescent dyes, 1-N-phenylnapthylamine and 3,3'-dipropylthiadicarbocyanine were used to analyze the outer membrane permeability and inner membrane depolarization of E. coli. The accumulation of fluoxetine in the treated E. coli was determined via HPLC. The active fraction of ATR was identified. RESULTS: The water extract of ATR significantly decreased the number of MDR mutants induced by fluoxetine and had half effective concentrations (EC50) of 55.5 μg/ml and 16.8 μg/ml for chloramphenicol and tetracycline, respectively. ATR robustly reversed the fluoxetine-induced superoxide response and membrane damage in E. coli. In addition, the inclusion of ATR significantly reduced the accumulation of fluoxetine in E. coli. After further fractionation, the polysaccharide of ATR was demonstrated as the fraction with the most significant anti-MDR activity. CONCLUSIONS: This is the first report to investigate the MDR-preventing effect of ATR. The results of this study proposed ATR as an excellent herbal product to prevent MDR issues, as induced by fluoxetine, with the potential to reduce the side effects during the drug therapy of depression.