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Microbial-Derived Tryptophan Metabolites and Their Role in Neurological Disease: Anthranilic Acid and Anthranilic Acid Derivatives.
The gut microbiome provides the host access to otherwise indigestible nutrients, which are often further metabolized by the microbiome into bioactive components. The gut microbiome can also shift the balance of host-produced compounds, which may alter host health. One precursor to bioactive metabolites is the essential aromatic amino acid tryptophan. Tryptophan is mostly shunted into the kynurenine pathway but is also the primary metabolite for serotonin production and the bacterial indole pathway. Balance between tryptophan-derived bioactive metabolites is crucial for neurological homeostasis and metabolic imbalance can trigger or exacerbate neurological diseases. Alzheimer's, depression, and schizophrenia have been linked to diverging levels of tryptophan-derived anthranilic, kynurenic, and quinolinic acid. Anthranilic acid from collective microbiome metabolism plays a complex but important role in systemic host health. Although anthranilic acid and its metabolic products are of great importance for host-microbe interaction in neurological health, literature examining the mechanistic relationships between microbial production, host regulation, and neurological diseases is scarce and at times conflicting. This narrative review provides an overview of the current understanding of anthranilic acid's role in neurological health and disease, with particular focus on the contribution of the gut microbiome, the gut-brain axis, and the involvement of the three major tryptophan pathways.
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Comparison of the Fecal Bacteriome of HIV-Positive and HIV-Negative Older Adults.
HIV infection is considered a scenario of accelerated aging. Previous studies have suggested a link between aging, frailty, and gut dysbiosis, but there is a knowledge gap regarding the HIV population. Our objective was to compare the fecal bacteriome of older people with HIV (PWH) and non-HIV controls, and to assess potential links between gut dysbiosis and frailty. A total of 36 fecal samples (24 from PWH and 12 from non-HIV controls) were submitted to a metataxonomic analysis targeting the V3-V4 hypervariable region of the 16S rRNA gene. High-quality reads were assembled and classified into operational taxonomic units. Alpha diversity, assessed using the Shannon index, was higher in the control group than in the HIV group (p < 0.05). The relative abundance of the genus Blautia was higher in the HIV group (p < 0.001). The presence of Blautia was also higher in PWH with depression (p = 0.004), whereas the opposite was observed for the genus Bifidobacterium (p = 0.004). Our study shows shifts in the composition of the PWH bacteriome when compared to that of healthy controls. To our knowledge, this is the first study suggesting a potential link between depression and gut dysbiosis in the HIV population.
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Bibliometric and Visual Analysis of Research on the Links Between the Gut Microbiota and Depression From 1999 to 2019.
Background: There is a crucial link between the gut microbiota and the host central nervous system, and the communication between them occurs via a bidirectional pathway termed the "microbiota-gut-brain axis." The gut microbiome in the modern environment has markedly changed in response to environmental factors. These changes may affect a broad range of host psychiatric disorders, such as depression, by interacting with the host through metabolic, immune, neural, and endocrine pathways. Nevertheless, the general aspects of the links between the gut microbiota and depression have not been systematically investigated through bibliometric analysis. Aim: This study aimed to analyze the current status and developing trends in gut microbiota research in the depression field through bibliometric and visual analysis. Methods: A total of 1,962 publications published between 1999 and 2019 were retrieved from the Web of Science Core Collection. CiteSpace (5.6 R5) was used to perform collaboration network analysis, co-citation analysis, co-occurrence analysis, and citation burst detection. Results: The number of publications has been rapidly growing since 2010. The collaboration network analysis revealed that the USA, University College Cork, and John F. Cryan were the most influential country, institute, and scholar, respectively. The most productive and co-cited journals were Brain Behavior and Immunity and Proceedings of the National Academy of Sciences of the United States of America, respectively. The co-citation analysis of references revealed that the most recent research focus was in the largest theme cluster, "cytokines," thus reflecting the important research foundation in this field. The co-occurrence analysis of keywords revealed that "fecal microbiota" and "microbiome" have become the top two research hotspots since 2013. The citation burst detection for keywords identified several keywords, including "Parkinson's disease," "microbiota-gut-brain axis," "microbiome," "dysbiosis," "bipolar disorder," "impact," "C reactive protein," and "immune system," as new research frontiers, which have currently ongoing bursts. Conclusions: These results provide an instructive perspective on the current research and future directions in the study of the links between the gut microbiota and depression, which may help researchers choose suitable cooperators or journals, and promote their research illustrating the underlying molecular mechanisms of depression, including its etiology, prevention, and treatment.
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The gut-brain connection: microbes' influence on mental health and psychological disorders.
The human gut microbiome has emerged as a pivotal modulator of brain function and mental health, acting through intricate bidirectional communication along the gut-brain axis. Mounting evidence suggests that microbial communities influence neurodevelopment, neurotransmission, and behavior via pathways involving the vagus nerve, immune signaling, and microbiota-derived metabolites such as short-chain fatty acids and neurotransmitter precursors. This review critically examines the mechanistic underpinnings of microbiota-brain communication and evaluates current findings linking dysbiosis to psychiatric conditions, including depression, anxiety, schizophrenia, autism spectrum disorder, and bipolar disorder. In addition, it assesses the therapeutic potential of microbiome-targeted interventions-such as probiotics, fecal microbiota transplantation (FMT), and precision dietary modulation-in ameliorating neuropsychiatric symptoms. While the field holds considerable promise, limitations, including correlational study designs, small sample sizes, and a lack of standardized methodologies, underscore the need for rigorous, large-scale clinical trials. A deeper understanding of host-microbe interactions may catalyze a paradigm shift in psychiatric treatment, paving the way for novel, personalized microbiome-based therapeutics.
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Associations of maternal prenatal psychological symptoms and saliva cortisol with neonatal meconium microbiota: A cross-sectional study.
UNLABELLED: Alterations in the diversity and relative abundances of the gut microbiome have been associated with a broad spectrum of medical conditions. Maternal psychological symptoms during pregnancy may impact on offspring development by altering the maternal and the foetal gut microbiome. We aimed to investigate whether self-reported maternal anxiety, depressive symptoms, and distress as well as saliva cortisol levels in late pregnancy alter the bacterial composition of the infant's meconium. METHODS: A total of N = 100 mother-infant pairs were included. Maternal psychological symptoms were measured using psychological questionnaires (EPDS, PSS-10, STAI) at 34-36 weeks gestation and salivary cortisol was measured at 34-36 and 38 weeks gestation. Infant meconium samples were collected in the first five days postpartum and analysed using 16S rRNA amplicon sequencing. RESULTS: Correlations showed that lower alpha diversity of the meconium microbiome was significantly associated with increased maternal prenatal depressive symptoms in late gestation (τ = -0.15, p = .04). Increased saliva cortisol AUCg at T2 was significantly related to higher beta diversity of the meconium samples (Pr(>F) = 0.003*). Pseudomonas was the most abundant phylum and was associated with maternal saliva cortisol total decline. No other associations were found. CONCLUSIONS: Maternal prenatal depressive symptoms are associated with infant faecal microbiome alpha diversity, whereas maternal saliva cortisol AUCg is linked to increased beta diversity and total decline related to increased Psuedomonas. Future studies are warranted to understand how these microbiota community alterations are linked to child health outcomes.
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Trihexyphenidyl Alters Its Host's Metabolism, Neurobehavioral Patterns, and Gut Microbiome Feedback Loop-The Modulating Role of Anacyclus pyrethrum.
Trihexyphenidyl (THP)-a synthetic anticholinergic medication used to manage parkinsonism and extrapyramidal symptoms-has gained significant clinical recognition. However, there is a critical gap in understanding its withdrawal effects. This study investigates the intricate interplay between gut microbiota and oxidative stress during THP withdrawal. Furthermore, it explores the therapeutic potential of Anacyclus pyrethrum (AEAP) for alleviating the associated adverse effects. This comprehensive research combines behavioral tests, biochemical analysis, gut microbiome assessment utilizing matrix-assisted laser desorption ionization-time of flight mass spectrometry (MALDI-TOF MS), and oxidative stress measures. The results reveal that the chronic administration of THP leads to severe withdrawal syndrome, marked by heightened anxiety, depressive-like behaviors, increased cortisol levels, elevated oxidative stress, and gut dysbiosis. However, the administration of AEAP alongside THP shows a significant capacity to mitigate these deleterious effects. Co-treatment and post-treatment with AEAP increased bacterial density and diversity, promoting the proliferation of beneficial bacteria associated with improved gut health. Furthermore, AEAP administration reduced cortisol levels and exhibited potent antioxidant properties, effectively countering the THP-induced oxidative damage. This study highlights the withdrawal effects of THP and underscores the therapeutic potential of AEAP for managing these symptoms. The findings reveal its promising effects in alleviating behavioral and biochemical impairments, reducing oxidative stress, and restoring gut microbiota, which could significantly impact the clinical management of THP withdrawal and potentially extend to other substance withdrawal scenarios.
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Nutritional psychology and inflammatory bowel disease: a narrative review of gut-brain axis interactions.
This paper explores the intricate relationship between Inflammatory Bowel Disease (IBD) and psychopathology, with a particular focus on anxiety and depression. This narrative review synthesizes recent findings on how dietary factors and nutritional psychology influence the gut-brain axis in patients with inflammatory bowel disease. The bidirectional gut-brain axis, chronic inflammation, and psychological stress are all key contributors to the mental health burden in IBD patients. The paper reviews the physiological mechanisms linking IBD and psychiatric symptoms, particularly how inflammation and gut microbiota composition may influence mood disorders. It addresses the variability in psychiatric comorbidities across IBD subtypes (Crohn's disease and ulcerative colitis) and highlights the challenges in standardized diagnosis and treatment. Emerging research on microbiome-based therapies, nutritional interventions, and personalized care approaches offers promising solutions for improving gastrointestinal and mental health outcomes. Integrating multidisciplinary care, involving gastroenterologists, psychiatrists, and dietitians, alongside advances in precision medicine, holds potential for developing more effective, individualized treatment strategies. However, challenges remain regarding variability in patient responses, methodological inconsistencies, and the need for standardized clinical protocols. The paper concludes by calling for further research to clarify these relationships and optimize treatment for IBD patients struggling with both physical and psychological health challenges.
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Correction for Taylor et al., "Depression in Individuals Coinfected with HIV and HCV Is Associated with Systematic Differences in the Gut Microbiome and Metabolome".
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Microbiome restoration diet improves digestion, cognition and physical and emotional wellbeing.
Manipulating gut bacteria in the microbiome, through the use of probiotics and prebiotics, has been found to have an influence on both physical and emotional wellbeing. This study uses a dietary manipulation 'The Gut Makeover' designed to elicit positive changes to the gut bacteria within the microbiome. 21 healthy participants undertook 'The Gut Makeover' for a four week period. Weight and various aspects of health were assessed pre and post intervention using the Functional Medicine Medical Symptoms Questionnaire (MSQ). Paired sample t-tests revealed a significant reduction in self-reported weight at the end of the intervention. Adverse medical symptoms related to digestion, cognition and physical and emotional wellbeing, were also significantly reduced during the course of the dietary intervention. The intervention, designed to manipulate gut bacteria, had a significant impact on digestion, reducing IBS type symptoms in this non-clinical population. There was also a striking reduction in negative symptoms related to cognition, memory and emotional wellbeing, including symptoms of anxiety and depression. Dietary gut microbiome manipulations may have the power to exert positive physical and psychological health benefits, of a similar nature to those reported in studies using pre and probiotics. The small sample size and lack of control over confounding variables means that it will be important to replicate these findings in larger-scale controlled, prospective, clinical trials. This dietary microbiome intervention has the potential to improve physical and emotional wellbeing in the general population but also to be investigated as a treatment option for individuals with conditions as diverse as IBS, anxiety, depression and Alzheimer's disease.
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Gut viral metagenomics identifies viral signatures and their role in depression.
BACKGROUND: The gut microbiome has been implicated in the onset and progression of depression. Yet, the role of the gut virome in depression remains unexplored, and a diagnostic model has not been satisfactorily constructed. METHODS: Herein, we analysed the gut virome profiles of 29 patients with depression and 33 healthy controls using bulk metagenome sequencing. RESULTS: A total of 45 differentially abundant viral taxa were identified, among which four, s_Stenotrophomonas_virus_Pokken, g_Pokkenvirus, s_Dickeya_virus_AD1, and g_Alexandravirus, demonstrated strong diagnostic potential (AUCs > 0.8). These four viruses also exhibited strong correlations, suggesting they may constitute a synergistic ecological cluster. Function annotation revealed seven metabolic pathways with significant differences, including alanine, aspartate, and glutamate metabolism, branched-chain amino acid (BCAA) biosynthesis, and energy metabolism in patients with depression. CONCLUSION: This study identified four distinct viral signatures for depression and proposes novel viral biomarkers for the diagnosis of depression, offering a robust diagnostic approach and new insights into the pathological mechanisms of depression.