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Resiliency among older adults receiving lung cancer treatment (ROAR-LCT): A novel supportive care intervention for older adults with advanced lung cancer.
INTRODUCTION: Novel supportive care interventions designed for an aging population with lung cancer are urgently needed. We aimed to determine the feasibility of a novel supportive care physical therapy (PT) plus progressive muscle relaxation (PMR) intervention delivered to older adults with advanced lung cancer in the United States (US). MATERIALS AND METHODS: This clinical trial, Resiliency Among Older Adults Receiving Lung Cancer Treatment (ROAR-LCT: NCT04229381), recruited adults aged ≥60 years with unresectable stage III/IV non-small cell (NSCLC) or small cell lung cancer (SCLC) receiving cancer treatment at The James Thoracic Oncology Center (planned enrollment, N = 20). There were no exclusion criteria pertaining to performance status, laboratory values, prior cancer diagnoses, comorbidities, or brain metastases. Participants were evaluated by PT and psychology and given an exercise pedaler, resistance bands, a relaxation voice recording, and instructions at study initiation. Participants were evaluated in-person by PTs and psychologists at the start and end of the 12-session intervention, with the intervening sessions conducted via virtual health. Participants completed self-reported measures of functional status, symptoms, and mood longitudinally with the following instruments: EQ-5D-5L, Patient Health Questionnaire-9, and General Anxiety Disorder-7. PT assessments included the Short Physical Performance Battery (SPPB) and the two-minute walk test. Feasibility was defined as at least 60% of participants completing at least 70% of all intervention sessions. Optional gut microbiome samples and activity monitoring data (ActiGraph®) were also collected. RESULTS: The ROAR-LCT study concluded after consenting 22 patients. Among the 22 consented, 18 (81.8%) started the intervention; 11 participants (61.1%) completed at least 70% of all study sessions. All participants with SCLC completed the intervention. Reasons for withdrawal included progression of disease or hospitalization. The majority (88.9%) of patients who started were able to complete at least one virtual health session. Participants' functional status, SPPB, depression, and anxiety scores were stable from pre- to post-intervention. Participants who withdrew had worse baseline scores across domains. Seven microbiome and six ActiGraph® samples were collected. DISCUSSION: This is one of the first PT + PMR supportive care interventions using virtual health among older adults with advanced lung cancer to achieve feasibility in the US.
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Metabolic and Microbiota Measures as Peripheral Biomarkers in Major Depressive Disorder.
Advances in understanding the role of the microbiome in physical and mental health are at the forefront of medical research and hold potential to have a direct impact on precision medicine approaches. In the past 7 years, we have studied the role of microbiota-brain communication on behavior in mouse models using germ-free mice, mice exposed to antibiotics, and healthy specific pathogen free mice. Through our work and that of others, we have seen an amazing increase in our knowledge of how bacteria signal to the brain and the implications this has for psychiatry. Gut microbiota composition and function are influenced both by genetics, age, sex, diet, life experiences, and many other factors of psychiatric and bodily disorders and thus may act as potential biomarkers of the gut-brain axis that could be used in psychiatry and co-morbid conditions. There is a particular need in major depressive disorder and other mental illness to identify biomarkers that can stratify patients into more homogeneous groups to provide better treatment and for development of new therapeutic approaches. Peripheral outcome measures of host-microbe bidirectional communication have significant translational value as biomarkers. Enabling stratification of clinical populations, based on individual biological differences, to predict treatment response to pharmacological and non-pharmacological interventions. Here we consider the links between co-morbid metabolic syndrome and depression, focusing on biomarkers including leptin and ghrelin in combination with assessing gut microbiota composition, as a potential tool to help identify individual differences in depressed population.
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Probiotics, prebiotics, and the host microbiome: the science of translation.
Recent advances in our understanding of the community structure and function of the human microbiome have implications for the potential role of probiotics and prebiotics in promoting human health. A group of experts recently met to review the latest advances in microbiota/microbiome research and discuss the implications for development of probiotics and prebiotics, primarily as they relate to effects mediated via the intestine. The goals of the meeting were to share recent advances in research on the microbiota, microbiome, probiotics, and prebiotics, and to discuss these findings in the contexts of regulatory barriers, evolving healthcare environments, and potential effects on a variety of health topics, including the development of obesity and diabetes; the long-term consequences of exposure to antibiotics early in life to the gastrointestinal (GI) microbiota; lactose intolerance; and the relationship between the GI microbiota and the central nervous system, with implications for depression, cognition, satiety, and mental health for people living in developed and developing countries. This report provides an overview of these discussions.
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Gut Microbial Signatures Can Discriminate Unipolar from Bipolar Depression.
Discriminating depressive episodes of bipolar disorder (BD) from major depressive disorder (MDD) is a major clinical challenge. Recently, gut microbiome alterations are implicated in these two mood disorders; however, little is known about the shared and distinct microbial characteristics in MDD versus BD. Here, using 16S ribosomal RNA (rRNA) gene sequencing, the microbial compositions of 165 subjects with MDD are compared with 217 BD, and 217 healthy controls (HCs). It is found that the microbial compositions are different between the three groups. Compared to HCs, MDD is characterized by altered covarying operational taxonomic units (OTUs) assigned to the Bacteroidaceae family, and BD shows disturbed covarying OTUs belonging to Lachnospiraceae, Prevotellaceae, and Ruminococcaceae families. Furthermore, a signature of 26 OTUs is identified that can distinguish patients with MDD from those with BD or HCs, with area under the curve (AUC) values ranging from 0.961 to 0.986 in discovery sets, and 0.702 to 0.741 in validation sets. Moreover, 4 of 26 microbial markers correlate with disease severity in MDD or BD. Together, distinct gut microbial compositions are identified in MDD compared to BD and HCs, and a novel marker panel is provided for distinguishing MDD from BD based on gut microbiome signatures.
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Psychobiotic Strategies for Managing Anxiety, Depression, and Schizophrenia: A Narrative Review.
The gut microbiome exerts significant influence over mental health through the bidirectional communication network of the gut-brain axis. Growing evidence implicates disruptions in gut microbial composition in the pathophysiology of a range of neuropsychiatric conditions, including anxiety, major depressive disorder (MDD), and schizophrenia. Psychobiotics have emerged as a promising adjunctive strategy for modulating mental health outcomes through several interconnected mechanisms, including neurotransmitter modulation, immune regulation, short-chain fatty acid production, and hypothalamic-pituitary-adrenal axis stabilization, among others. This narrative review, intended for clinicians and researchers in integrative and functional medicine, synthesizes current clinical and translational evidence for probiotic interventions across anxiety, MDD, bipolar disorder, and schizophrenia, highlighting key strains, mechanisms, and outcomes. Findings demonstrate that specific Lactobacillus and Bifidobacterium strains show measurable benefit in reducing anxiety and depressive symptom severity, while emerging evidence suggests potential utility in psychotic disorders. Limitations include significant heterogeneity in strain selection, dosing protocols, study populations, and outcome measures, which constrain clinical translation. Future research should prioritize standardized protocols, longitudinal designs, and functional microbiome profiling to support personalized, microbiome-informed approaches to mental health care.
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The Role of Oxidative Stress in Common Risk Factors and Mechanisms of Cardio-Cerebrovascular Ischemia and Depression.
The public health sector faces a huge challenge as a result of the high prevalence and burden of disability caused by ischemic cardio-cerebrovascular disease (CVD) and depression. Although studies have explored the underlying mechanisms and potential therapies to address conditions, there is no treatment breakthrough, especially for depression which is highly influenced by social stressors. However, accumulating evidence reveals that CVD and depression are correlated and share common risk factors, particularly obesity, diabetes, and hypertension. They also share common mechanisms, including oxidative stress (OS), inflammation and immune response, cell death signaling pathway, and microbiome-gut-brain axis. This review summarizes the relationship between ischemic CVD and depression and describes the interactions among common risk factors and mechanisms for these two diseases. In addition, we propose that OS mediates the crosstalk between these diseases. We also reveal the potential of antioxidants to ameliorate OS-related injuries.
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Dysbiosis: A Potential Precursor to the Development of a Depressive Disorder.
Background: Although previous investigations have indicated that gastrointestinal pathologies facilitate the occurrence of mood disorders, there is a lack of studies based on data from clinical practice. The aim of this study was to investigate the incidence of depression in patients with dysbiosis. Methods: Adult patients (≥18 years) from 1193 general practices in Germany between January 2005 and December 2018 with an initial diagnosis of dysbiosis documented anonymously in the Disease Analyzer database (IQVIA) were analyzed. The incidence of depression diagnoses as a function of dysbiosis was calculated and multivariate regression models were applied. Results: This study included 552 patients with and 552 patients without dysbiosis. Within five years of the index date, 20.5% of patients with dysbiosis and 5.5% of individuals without dysbiosis had been diagnosed with depression (p < 0.001). Dysbiosis was found to be significantly associated with the incidence of depression (HR: 2.85 (95% CI: 2.00−4.04)). This association was slightly stronger in men (HR: 3.54) than in women (HR: 2.61) and was more pronounced in the age group >60 years (HR: 4.43). Conclusions: We identified dysbiosis as a risk factor for developing depression within 5 years after the index date. This risk seems to be higher in male than in female patients.
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A critical analysis of eating disorders and the gut microbiome.
The gut microbiota, also known as our "second brain" is an exciting frontier of research across a multitude of health domains. Gut microbes have been implicated in feeding behaviour and obesity, as well as mental health disorders including anxiety and depression, however their role in the development and maintenance of eating disorders (EDs) has only recently been considered. EDs are complex mental health conditions, shaped by a complicated interplay of factors. Perhaps due to an incomplete understanding of the etiology of EDs, treatment remains inadequate with affected individuals likely to face many relapses. The gut microbiota may be a missing piece in understanding the etiology of eating disorders, however more robust scientific inquiry is needed in the field before concrete conclusions can be made. In this spotlight paper, we critically evaluate what is known about the bi-directional relationship between gut microbes and biological processes that are implicated in the development and maintenance of EDs, including physiological functioning, hormones, neurotransmitters, the central nervous system, and the immune system. We outline limitations of current research, propose concrete steps to move the field forward and, hypothesize potential clinical implications of this research. Our gut is inhabited by millions of bacteria which have more recently been referred to as "our second brain". In fact, these microbes are thought to play a role in ED behaviour, associated anxiety and depression, and even affect our weight. Recent research has dove into this field with promising findings that have the potential to be applied clinically to improve ED recovery. The present paper discusses what is known about the gut microbiome in relation to EDs and the promising implications that leveraging this knowledge, through fecal microbiome transplants, probiotics, and microbiome-directed supplemental foods, could have on ED treatment.
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Pathophysiology linking depression and type 2 diabetes: Psychotherapy, physical exercise, and fecal microbiome transplantation as damage control.
Diabetes increases the likelihood of developing depression and vice versa. Research on this bidirectional association has somewhat managed to delineate the interplay among implicated physiological processes. Still, further exploration is required in this context. This review addresses the comorbidity by investigating suspected common pathophysiological mechanisms. One such factor is psychological stress which disturbs the hypothalamic-pituitary-adrenal axis causing hormonal imbalance. This includes elevated cortisol levels, a common biomarker of both depression and diabetes. Disrupted insulin signaling drives the hampered neurotransmission of serotonin, dopamine, and norepinephrine. Also, adipokine hormones such as adiponectin, leptin, and resistin and the orexigenic hormone, ghrelin, are involved in both depression and T2DM. This disarray further interferes with physiological processes encompassing sleep, the gut-brain axis, metabolism, and mood stability. Behavioral coping mechanisms, such as unhealthy eating, mediate disturbed glucose homeostasis, and neuroinflammation. This is intricately linked to oxidative stress, redox imbalance, and mitochondrial dysfunction. However, interventions such as psychotherapy, physical exercise, fecal microbiota transplantation, and insulin-sensitizing agents can help to manage the distressing condition. The possibility of glucagon-like peptide 1 possessing a therapeutic role has also been discussed. Nonetheless, there stands an urgent need for unraveling new correlating targets and biological markers for efficient treatment.
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Quercetin as a Novel Antidepressant: Mechanistic Insights into Its Neuroprotective and Anti-inflammatory Effects.
Depression is a globally recognized leading cause of mental health disability and mortality worldwide, severely affecting individuals' daily lives and relationships. At present, the limitation of first-line antidepressants has brought great difficulties to the treatment of depression. Therefore, the development of new antidepressants is imminent. Quercetin is considered as a potential antidepressant drug due to its potent anti-inflammatory, antioxidant, and neuroprotective effects. We explored the antidepressant effect of quercetin by establishing a mouse model (Adult male C57BL/6 J mice) of depression induced by chronic unpredictable stress (CUS). Analysis of the antidepressant effect of quercetin was conducted using multi-omics. The sociability and the protein expression levels of Hsp90, XBP1 and iNOS in the hippocampus of mice were evaluated through behavioral and molecular biology experiments. We found that quercetin treatment alleviated social impairment in mice and could target Hsp90 to inhibit the upregulation of XBP1 and iNOS. In addition, based on microbiome as well as untargeted metabolomics results of hippocampal brain regions, quercetin was found to increase the abundance of Lactobacillus and modulate the levels of inosine, Creatinine, and Lithocholic acid metabolites in the hippocampus. To sum up, in the present study, we revealed the molecular mechanism of quercetin alleviating depression-like behavior in CUS mice by inhibiting CUS-induced endoplasmic reticulum stress, neuroinflammation, gut microbiota dysbiosis, and metabolic disorders through multi-omics joint analysis. This provides a complementary scientific explanation for the antidepressant effects of quercetin.