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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.
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Autointoxication and historical precursors of the microbiome-gut-brain axis.
This article focuses on autointoxication, a discredited medical theory from the late nineteenth century that provides important points of reflection for today's research on the role of microbes in the human gut for mental health. It considers how the theory of autointoxication, which came into great prominence amongst physicians and the general public worldwide, fell from grace by the middle of the twentieth century, and briefly asks why studies of the human microbiome are now back in vogue. It departs from earlier articles on the topic firstly by arguing that autointoxication theory was especially prevalent in France, and secondly by focusing on the application of this theory to mental health. Bringing to light medical treatises and theses from this period which have so far remained unexamined, it shows that examining the development and reception of medical theories form the past can help us today in understanding both the pitfalls and promise of research in this area.
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A Holistic Perspective on How Photobiomodulation May Influence Fatigue, Pain, and Depression in Inflammatory Bowel Disease: Beyond Molecular Mechanisms.
BACKGROUND: Numerous mechanisms, mostly molecular, have been tested and proposed for photobiomodulation. Photobiomodulation is finding a niche in the treatment of conditions that have no gold-standard treatment or only partially effective pharmacological treatment. Many chronic conditions are characterised by symptoms for which there is no cure or control and for which pharmaceuticals may add to the disease burden through side effects. To add quality to life, alternate methods of symptom management need to be identified. OBJECTIVE: To demonstrate how photobiomodulation, through its numerous mechanisms, may offer an adjunctive therapy in inflammatory bowel disease. Rather than considering only molecular mechanisms, we take an overarching biopsychosocial approach to propose how existing evidence gleaned from other studies may underpin a treatment strategy of potential benefit to people with Crohn's disease and ulcerative colitis. MAIN FINDINGS: In this paper, the authors have proposed the perspective that photobiomodulation, through an integrated effect on the neuroimmune and microbiome-gut-brain axis, has the potential to be effective in managing the fatigue, pain, and depressive symptoms of people with inflammatory bowel disease.
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Lung inflammation and disease: A perspective on microbial homeostasis and metabolism.
It is now well appreciated that the human microbiome plays a significant role in a number of processes in the body, significantly affecting its metabolic, inflammatory, and immune homeostasis. Recent research has revealed that almost every mucosal surface in the human body is associated with a resident commensal microbiome of its own. While the gut microbiome and its role in regulation of host metabolism along with its alteration in a disease state has been well studied, there is a lacuna in understanding the resident microbiota of other mucosal surfaces. Among these, the scientific information on the role of lung microbiota in pulmonary diseases is currently severely limited. Historically, lungs have been considered to be sterile and lung diseases have only been studied in the context of bacterial pathogenesis. Recently however, studies have revealed a resilient microbiome in the upper and lower respiratory tracts and there is increased evidence on its central role in respiratory diseases. Knowledge of lung microbiome and its metabolic fallout (local and systemic) is still in its nascent stages and attracting immense interest in recent times. In this review, we will provide a perspective on lung-associated metabolic disorders defined for lung diseases (e.g., chronic obstructive pulmonary disease, asthma, and respiratory depression due to infection) and correlate it with lung microbial perturbation. Such perturbations may be due to altered biochemical or metabolic stress as well. Finally, we will draw evidence from microbiome and classical microbiology literature to demonstrate how specific lung morbidities associate with specific metabolic characteristics of the disease, and with the role of microbiome in this context. © 2018 IUBMB Life, 71(1):152-165, 2019.
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Impact of small intestinal bacterial overgrowth on symptoms and quality of life in irritable bowel syndrome.
OBJECTIVE: To explore the factors associated with small intestinal bacterial overgrowth (SIBO), and to further evaluate the impact of SIBO on irritable bowel syndrome (IBS) in terms of symptom severity and health-related quality of life (HRQoL). METHODS: A cross-sectional study of consecutive adult patients who underwent glucose hydrogen breath test was conducted. Factors associated with SIBO were evaluated. Symptom severity and HRQoL of IBS patients with and without SIBO were compared. The independent factors associated with severe IBS were explored. RESULTS: A total of 160 patients were included (median age 40 years, males 31.3%). IBS was present among 53.8% of subjects, with 33.8% having diarrhea-predominant IBS (IBS-D). SIBO was diagnosed in 22.5% of the study population. Patients with SIBO were more commonly diagnosed with IBS-D than those without (50.0% vs 29.0%, P = 0.019). Severe IBS was associated with SIBO (36.4% vs 15.6%, P = 0.043). SIBO was associated with poorer HRQoL (Euroqol five-dimensional utility score: 0.73 vs 0.80, P = 0.024). SIBO (44.4% vs 20.6%, P = 0.043), anxiety (77.8% vs. 39.7%, P = 0.004), and depression (50.0% vs 19.1%, P = 0.011) were associated with severe IBS in the univariate analysis. However, SIBO was the only independent factor associated with severe IBS in the multivariate analysis (adjusted odds ratio 3.83, 95% confidence interval CI 1.02-14.34, P = 0.046). CONCLUSIONS: There was a significant association between IBS-D and SIBO. The coexistence of SIBO had a significant negative impact on IBS patients.
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Altered brain structural connectivity in patients with longstanding gut inflammation is correlated with psychological symptoms and disease duration.
OBJECTIVE: We aimed to identify differences in network properties of white matter microstructure between asymptomatic ulcerative colitis (UC) participants who had a history of chronic gut inflammation, healthy controls (HCs) and a disease control group without gut inflammation (irritable bowel syndrome; IBS). DESIGN: Diffusion weighted imaging was conducted in age and sex-matched participants with UC, IBS, and HCs (N = 74 each), together with measures of gastrointestinal and psychological symptom severity. Using streamline connectivity matrices and graph theory, we aimed to quantify group differences in brain network connectivity. Regions showing group connectivity differences were correlated with measures showing group behavioral and clinical differences. RESULTS: UC participants exhibited greater centrality in regions of the somatosensory network and default mode network, but lower centrality in the posterior insula and globus pallidus compared to HCs (q < 0.05). Hub analyses revealed compromised hubness of the pallidus in UC and IBS compared to HCs which was replaced by increased hubness of the postcentral sulcus. Surprisingly, few differences in network matrices between UC and IBS were identified. In UC, centrality measures in the secondary somatosensory cortex were associated with depression (q < 0.03), symptom related anxiety (q < 0.04), trait anxiety (q < 0.03), and symptom duration (q < 0.05). CONCLUSION: A history of UC is associated with neuroplastic changes in several brain networks, which are associated with symptoms of depression, trait and symptom-related anxiety, as well as symptom duration. When viewed together with the results from IBS subjects, these findings suggest that chronic gut inflammation as well as abdominal pain have a lasting impact on brain network organization, which may play a role in symptoms reported by UC patients, even when gut inflammation has subsided.