Personalized Response of Parkinson's Disease Gut Microbiota to Nootropic Medicinal Herbs In Vitro: A Proof of Concept.

Parkinson's disease (PD) is a neurodegenerative disease characterized by the loss of dopaminergic neurons. Although the etiology of PD remains elusive, it has been hypothesized that initial dysregulation may occur in the gastrointestinal tract and may be accompanied by gut barrier defects. A strong clinical interest in developing therapeutics exists, including for the treatment of gut microbiota and physiology. We previously reported the impact of healthy fecal microbiota anaerobic cultures supplemented with nootropic herbs. Here, we evaluated the effect of nootropic Ayurvedic herbs on fecal microbiota derived from subjects with PD in vitro using 16S rRNA sequencing. The microbiota underwent substantial change in response to each treatment, comparable in magnitude to that observed from healthy subjects. However, the fecal samples derived from each participant displayed unique changes, consistent with a personalized response. We used genome-wide metabolic reconstruction to predict the community's metabolic potential to produce products relevant to PD pathology, including SCFAs, vitamins and amino acid degradation products. These results suggest the potential value of conducting in vitro cultivation and analyses of PD stool samples as a means of prescreening patients to select the medicinal herbs for which that individual is most likely to respond and derive benefit.

Alteration of Community Metabolism by Prebiotics and Medicinal Herbs.

Several studies have examined the impact of prebiotics on gut microbiota and associated changes in host physiology. Here, we used the in vitro cultivation of human fecal samples stimulated with a series of chemically related prebiotics and medicinal herbs commonly used in Ayurvedic medicine, followed by 16S rRNA sequencing. We applied a genome-wide metabolic reconstruction of enumerated communities to compare and contrast the structural and functional impact of prebiotics and medicinal herbs. In doings so, we examined the relationships between discrete variations in sugar composition and sugar linkages associated with each prebiotic to drive changes in microbiota composition. The restructuring of microbial communities with glycan substrates alters community metabolism and its potential impact on host physiology. We analyzed sugar fermentation pathways and products predicted to be formed and prebiotic-induced changes in vitamin and amino acid biosynthesis and degradation. These results highlight the utility of combining a genome-wide metabolic reconstruction methodology with 16S rRNA sequence-based community profiles to provide insights pertaining to community metabolism. This process also provides a rational means for prioritizing in vivo analysis of prebiotics and medicinal herbs in vivo to test hypotheses related to therapeutic potential in specific diseases of interest.

Current Approaches to Yoga in U.S. Medical Schools: Scoping Review of the Literature.

Background: Yoga is described as a system of physical and mental practices originating from India that connects mind, body, and spirit with techniques such as physical exercises, breathing, and meditation to promote health and well-being. Medical students experience an immense amount of stress that unfortunately continues throughout their residency and careers. Yoga represents a tool to reduce stress and support medical student resilience. Objective: This study aims to evaluate the current approaches to yoga in U.S. medical schools. Methods: A scoping literature review was conducted using search terms such as "medical school," "medical student," "medical education," "yoga," "asana," "pranayama," and "mindfulness." The primary aim of the review was to examine if U.S. medical schools offer accessible yoga to medical students and the characteristics of those yoga programs. Results: The search yielded 1313 primary articles. All titles and abstracts were screened for eligibility. Duplicate articles were removed, and 156 articles were reviewed independently by two authors. A total of eight articles met all the criteria. Yoga is offered in medical schools through three main models: recreational, research, and educational. All of the studies indicated various positive effects on medical students from these yoga programs, including in psychological states, perceived stress, and scores on medical knowledge assessments. Conclusions: Yoga aligns well with the objectives of medical education by combining physician resiliency, mindfulness, and education that can ultimately serve patients. Greater opportunities should be created to engage medical students in yoga through the length of their entire undergraduate and graduate medical training.

Short-Chain Fatty Acids Modulate Healthy Gut Microbiota Composition and Functional Potential.

Many studies have focused on the metabolic capacity of human gut microbiota to produce short-chain fatty acids and subsequent effects on host physiology. Given scarce data on how SCFAs produced by gut bacteria participate in cross-feeding to influence community structure and function, we evaluated the potential of SCFAs to modulate human gut microbiota in vitro. We employed anaerobic fecal cultivation in chemically defined medium supplemented with one of nine SCFAs to determine effects on both gut microbial community structure via 16S rRNA sequencing and function via genome reconstruction analysis. Each SCFA displayed significant and unique modulatory potential with respect to the relative abundance of bacterial taxa. Analysis of SCFA-supplemented communities revealed that alterations of individual closely related phylotypes displayed coherent changes, although exceptions were also observed which suggest strain-dependent differences in SCFA-induced changes. We used genome reconstruction to evaluate the functional implications of SCFA-mediated restructuring of fecal communities. We note that some SCFA-supplemented cultures displayed a reduction in the predicted abundance of SCFA producers, which suggests a possible undefined negative feedback mechanism. We conclude that SCFAs are not simply end-products of metabolism but also serve to modulate the gut microbiota through cross-feeding that alters the fitness of specified taxa. These results are important in the identification of prebiotics that elevate specific SCFAs for therapeutic benefit and highlight SCFA consumers as a salient part of the overall metabolic flux pertaining to bacterial fermentative processes.

Implications for Systemic Approaches to COVID-19: Effect Sizes of Remdesivir, Tocilizumab, Melatonin, Vitamin D3, and Meditation.

INTRODUCTION: COVID-19 poses a chronic threat to inflammatory systems, reinforcing the need for efficient anti-inflammatory strategies. The purpose of this review and analysis was to determine the efficacy of various interventions upon the inflammatory markers most affected by COVID-19. The focus was on the markers associated with COVID-19, not the etiology of the virus itself. METHODS: Based on 27 reviewed papers, information was extracted on the effects of COVID-19 upon inflammatory markers, then the effects of standard treatments (Remdesivir, Tocilizumab) and adjunctive interventions (vitamin D3, melatonin, and meditation) were extracted for those markers. These data were used to approximate effect sizes for the disease or interventions via standardized mean differences (SMD). RESULTS: The data that were available indicated that adjunctive interventions affected 68.4% of the inflammatory markers impacted by COVID-19, while standard pharmaceutical medication affected 26.3%. DISCUSSION: Nonstandard adjunctive care appeared to have comparable or superior effects in comparison to Remdesivir and Tocilizumab on the inflammatory markers most impacted by COVID-19. Alongside standards of care, melatonin, vitamin D3, and meditation should be considered for treatment of SARS-COV-2 infection and COVID-19 disease.

B Vitamins and Their Role in Immune Regulation and Cancer.

B group vitamins represent essential micronutrients for myriad metabolic and regulatory processes required for human health, serving as cofactors used by hundreds of enzymes that carry out essential functions such as energy metabolism, DNA and protein synthesis and other critical functions. B vitamins and their corresponding vitamers are universally essential for all cellular life forms, from bacteria to humans. Humans are unable to synthesize most B vitamins and are therefore dependent on their diet for these essential micronutrients. More recently, another source of B vitamins has been identified which is derived from portions of the 1013 bacterial cells inhabiting the gastrointestinal tract. Here we review the expanding literature examining the relationship between B vitamins and the immune system and diverse cancers. Evidence of B vitamin's role in immune cell regulation has accumulated in recent years and may help to clarify the disparate findings of numerous studies attempting to link B vitamins to cancer development. Much work remains to be carried out to fully clarify these relationships as the complexity of B vitamins' essential functions complicates an unequivocal assessment of their beneficial or detrimental effects in inflammation and cancers.

Dysfunction of the Microbiota-Gut-Brain Axis in Neurodegenerative Disease: The Promise of Therapeutic Modulation With Prebiotics, Medicinal Herbs, Probiotics, and Synbiotics.

Recent data suggest gut microbiota dysbiosis as a contributing factor in neurodegenerative diseases, such as Parkinson's Disease (PD) and Alzheimer's Disease (AD), and these pathologies may manifest via the microbiota-gut-brain-axis, which comprises bidirectional communication through neuroimmune, neuroendocrine, and direct neural pathways such as the vagus nerve. Preclinical and human clinical trial data reveal exciting potential for novel treatment targets and therapeutic modulation with prebiotics, medicinal herbs, probiotics, and synbiotics in health, aging, and neurodegeneration and are reviewed here. While greater insights and characterization of the microbiota-gut-brain axis have been revealed over the past decade, salient questions related to the pathology, pathogenesis and clinical treatment of the axis in the context of both health and neurodegenerative disease remain and are discussed in this review. Future directions such as additional well-controlled, large scale, longitudinal human clinical trials are urgently needed to further elucidate both mechanism and therapeutic opportunity in health, neurological disease, and disease subpopulations to ensure that the next decade ushers the dawn of targeted therapeutic modulation of the microbiota-gut-brain axis.

Changes in Continuous, Long-Term Heart Rate Variability and Individualized Physiological Responses to Wellness and Vacation Interventions Using a Wearable Sensor.

There are many approaches to maintaining wellness, including taking a simple vacation to attending highly structured wellness retreats, which typically regulate the attendee's personal time and activities. In a healthy English-speaking cohort of 112 women and men (aged 30-80 years), this study examined the effects of participating in either a 6-days intensive wellness retreat based on Ayurvedic medicine principles or unstructured 6-days vacation at the same wellness center setting. Heart rate variability (HRV) was monitored continuously using a wearable ECG sensor patch for up to 7 days prior to, during, and 1-month following participation in the interventions. Additionally, salivary cortisol levels were assessed for all participants at multiple times during the day. Continual HRV monitoring data in the real-world setting was seen to be associated with demographic [HRVALF: ßAge = 0.98 (95% CI = 0.96-0.98), false discovery rate (FDR) < 0.001] and physiological characteristics [HRVPLF: ß = 0.98 (95% CI = 0.98-1), FDR =0.005] of participants. HRV features were also able to quantify known diurnal variations [HRVLF/HF: ßACT:night vs. early-morning = 2.69 (SE = 1.26), FDR < 0.001] along with notable inter- and intraperson heterogeneity in response to intervention. A statistically significant increase in HRVALF [ß = 1.48 (SE = 1.1), FDR < 0.001] was observed for all participants during the resort visit. Personalized HRV analysis at an individual level showed a distinct individualized response to intervention, further supporting the utility of using continuous real-world tracking of HRV at an individual level to objectively measure responses to potentially stressful or relaxing settings.

16S rRNA gene profiling and genome reconstruction reveal community metabolic interactions and prebiotic potential of medicinal herbs used in neurodegenerative disease and as nootropics.

The prebiotic potential of nervine herbal medicines has been scarcely studied. We therefore used anaerobic human fecal cultivation to investigate whether medicinal herbs commonly used as treatment in neurological health and disease in Ayurveda and other traditional systems of medicine modulate gut microbiota. Profiling of fecal cultures supplemented with either Kapikacchu, Gotu Kola, Bacopa/Brahmi, Shankhapushpi, Boswellia/Frankincense, Jatamansi, Bhringaraj, Guduchi, Ashwagandha or Shatavari by 16S rRNA sequencing revealed profound changes in diverse taxa. Principal coordinate analysis highlights that each herb drives the formation of unique microbial communities predicted to display unique metabolic potential. The relative abundance of approximately one-third of the 243 enumerated species was altered by all herbs. Additional species were impacted in an herb-specific manner. In this study, we combine genome reconstruction of sugar utilization and short chain fatty acid (SCFA) pathways encoded in the genomes of 216 profiled taxa with monosaccharide composition analysis of each medicinal herb by quantitative mass spectrometry to enhance the interpretation of resulting microbial communities and discern potential drivers of microbiota restructuring. Collectively, our results indicate that gut microbiota engage in both protein and glycan catabolism, providing amino acid and sugar substrates that are consumed by fermentative species. We identified taxa that are efficient amino acid fermenters and those capable of both amino acid and sugar fermentation. Herb-induced microbial communities are predicted to alter the relative abundance of taxa encoding SCFA (butyrate and propionate) pathways. Co-occurrence network analyses identified a large number of taxa pairs in medicinal herb cultures. Some of these pairs displayed related culture growth relationships in replicate cultures highlighting potential functional interactions among medicinal herb-induced taxa.

Relationships among classifications of ayurvedic medicine diagnostics for imbalances and western measures of psychological states: An exploratory study.

BACKGROUND: According to Ayurveda, the traditional medical system of India, doshas are a combination of characteristics based on a five-element philosophy that drive our mental and physical tendencies. When the doshas, or functional principles, are out of balance in quality or quantity, wellbeing is adversely affected and symptoms manifest. OBJECTIVE: This study examined relationships among imbalances in the doshas (termed Vikruti) reported via questionnaire and Western measures of psychological states. MATERIALS AND METHODS: Study participants were 101 women (n = 81) and men (n = 20), mean age 53.9 years (SD = 11.7; range 32-80). Participants completed questionnaires to categorize their Vikruti type and psychological states, which included depressed mood (CESD), anxiety (PROMIS), rumination & reflection (RRQ), mindfulness (MAAS), stress (PSS), and quality of life (Ryff). RESULTS: Multivariate general linear modeling, controlling for age, gender and body mass index (BMI), showed that Vata imbalance was associated with more anxiety (p ≤ 0.05), more rumination (p ≤ 0.01), less mindfulness (p ≤ 0.05), and lower overall quality of life (p ≤ 0.01). Pitta imbalance was associated with poorer mood (p ≤ 0.01) and less mindfulness (p ≤ 0.05), more anxiety (p ≤ 0.05) and stress (p ≤ 0.05). Kapha imbalance was associated with more stress (p ≤ 0.05), more rumination (p ≤ 0.05) and less reflection (p ≤ 0.05). CONCLUSION: These findings suggest that symptoms of mind-body imbalances in Ayurveda are differentially associated with western assessments of psychological states. Ayurvedic dosha assessment may be an effective way to assess physical as well as emotional wellbeing in research and clinical settings.

Neuroimmune Mechanisms of Depression in Adults with Heart Failure.

Heart failure (HF) is a major and costly public health concern, and its prognosis is grim-with high hospitalization and mortality rates. HF affects millions of individuals across the world, and this condition is expected to become "the epidemic" of the twenty-first century (Jessup et al., 2016). It is well documented that individuals with HF experience disproportionately high rates of depression and that those who are depressed have worse clinical outcomes than their nondepressed counterparts. The purpose of this chapter is to introduce the reader to the study of depression in HF, and how psychoneuroimmunologic principles have been applied to further elucidate mechanisms (i.e., neurohormonal and cytokine activation) linking these comorbid disorders.

Prebiotic Potential of Herbal Medicines Used in Digestive Health and Disease.

INTRODUCTION: The prebiotic potential of herbal medicines has been scarcely studied. METHODS: The authors therefore used anaerobic human fecal cultivation to investigate whether three herbal medicines commonly used in gastrointestinal health and disease in Ayurveda alter the growth and abundance of specific bacterial species. RESULTS: Profiling of cultures supplemented with Glycyrrhiza glabra, Ulmus rubra, or triphala formulation by 16S rDNA sequencing revealed profound changes in diverse taxa in human gut microbiota. Principal coordinate analysis highlights that each herbal medicine drives the formation of unique microbial communities. The relative abundance of approximately one-third of the 299 species profiled was altered by all 3 medicines, whereas additional species displayed herb-specific alterations. Herb supplementation increased the abundance of many bacteria known to promote human health, including Bifidobacterium spp., Lactobacillus spp., and Bacteroides spp. Herb supplementation resulted in the reduced relative abundance of many species, including potential pathogens such as Citrobacter freundii and Klebsiella pneumoniae. Herbal medicines induced blooms of butyrate- and propionate-producing species. U. rubra and triphala significantly increased the relative abundance of butyrate-producing bacteria, whereas G. glabra induced the largest increase in propionate-producing species. To achieve greater insight into the mechanisms through which herbal medicines alter microbial communities, the authors assessed the shifts in abundance of glycosyl hydrolase families induced by each herbal medicine. Herb supplementation, particularly G. glabra, significantly increased the representation and potential expression of several glycosyl hydrolase families. DISCUSSION: These studies are novel in highlighting the significant prebiotic potential of medicinal herbs and suggest that the health benefits of these herbs are due, at least in part, to their ability to modulate the gut microbiota in a manner predicted to improve colonic epithelium function, reduce inflammation, and protect from opportunistic infection. Forthcoming studies in human clinical trials will test the concordance of the results generated in vitro and the predictions made by genome analyses.

Change in Sense of Nondual Awareness and Spiritual Awakening in Response to a Multidimensional Well-Being Program.

OBJECTIVE: This study examined the effects of a comprehensive mind-body program on sense of nondual awareness and spiritual awakening. DESIGN AND INTERVENTION: The study compared the effects of participation in an intensive 6-day Ayurveda-based mind-body program that addressed physical, emotional, and spiritual domains as compared with a control condition. SETTING: Resort setting. SUBJECTS: Participants were 69 healthy women and men (mean age 53.9 years; range 32-86). OUTCOME MEASURE: The primary outcome was the Nondual Embodiment Thematic Inventory (NETI). RESULTS: A significant group by time interaction (p = 0.029) indicated that after the intervention, participants in the mind-body program showed a significant increase in NETI scores (p < 0.03), which was sustained 1 month later (p < 0.01). CONCLUSION: Findings suggest that an intensive program providing holistic instruction and experience in mind-body practices can lead to a significant and sustained shift in perception of self-awareness, one that is likely favorable to well-being.

Advancing Research on Traditional Whole Systems Medicine Approaches.

While the intention of Integrative Medicine (IM) is whole person medicine, it has for the most part remained driven by individual modalities. Like the practice of IM itself, IM research too has been driven primarily by studies on individual modalities. There are significant challenges to moving research on whole systems medicine forward, with funding being at the top of the list. Historically, NIH has not been receptive to supporting research on whole systems, preferring instead to support studies that are more individual modality driven so that mechanisms can be identified. Purely mechanistic research, however, assumes unidirectional causality and linear responses yet clinical responses to whole systems approaches are more often multidirectional and dynamically unpredictable. The concept of emergence is applicable here. Whole systems approaches suggest that by incorporating therapies into holistic treatment programs we not only treat symptoms but accomplish more by activating the body's inherent self-organizing healing mechanisms and treat the root cause of illnesses as well as associated symptoms. Given that interest in integrative therapies with the general public and medical community is steadily increasing, there is need for more research that explores intact whole systems approaches to elucidate the relevant system-wide effects and dynamic interactions related to these practices.

Effects of Shambhavi Mahamudra Kriya, a Multicomponent Breath-Based Yogic Practice ( Pranayama), on Perceived Stress and General Well-Being.

Stress-induced disorders such as anxiety represent the leading causes of adult disability worldwide. Previous studies indicate that yoga and other contemplative practices such as pranayama, or controlled yogic breathing techniques, may be effective in the treatment of mood disorders and stress. In this study, 142 individuals (mean age = 43 years; SD = 13.90) participated in a 3-day retreat program during which they learned Shambhavi Mahamudra kriya, which is a yogic practice that includes both deep breathing and meditation techniques. Participants were instructed to practice the kriya each day for 21 minutes. After 6 weeks of daily practice, participants reported subjectively lower levels of perceived stress (Perceived Stress Scale) and higher levels of general well-being (General Well-Being Scale) compared to baseline. These results support the notion that Shambhavi Mahamudra kriya may represent a natural treatment for stress reduction.

Therapeutic Uses of Triphala in Ayurvedic Medicine.

AIM: The aim of this article is to review the current literature on the therapeutic uses and efficacy of Triphala. Herbal remedies are among the most ancient medicines used in traditional systems of healthcare such as Ayurveda. Triphala, a well-recognized and highly efficacious polyherbal Ayurvedic medicine consisting of fruits of the plant species Emblica officinalis (Amalaki), Terminalia bellerica (Bibhitaki), and Terminalia chebula (Haritaki), is a cornerstone of gastrointestinal and rejuvenative treatment. METHODS: A search of the PubMed database was conducted. RESULTS: In addition, numerous additional therapeutic uses described both in the Ayurvedic medical literature and anecdotally are being validated scientifically. In addition to laxative action, Triphala research has found the formula to be potentially effective for several clinical uses such as appetite stimulation, reduction of hyperacidity, antioxidant, anti-inflammatory, immunomodulating, antibacterial, antimutagenic, adaptogenic, hypoglycemic, antineoplastic, chemoprotective, and radioprotective effects, and prevention of dental caries. Polyphenols in Triphala modulate the human gut microbiome and thereby promote the growth of beneficial Bifidobacteria and Lactobacillus while inhibiting the growth of undesirable gut microbes. The bioactivity of Triphala is elicited by gut microbiota to generate a variety of anti-inflammatory compounds. CONCLUSIONS: This review summarizes recent data on pharmacological properties and clinical effects of Triphala while highlighting areas in need of additional investigation and clinical development.

The Effects of Stress and Meditation on the Immune System, Human Microbiota, and Epigenetics.

Context • Globally, more than 25% of individuals are affected by anxiety and depression disorders. Meditation is gaining popularity in clinical settings and its treatment efficacy is being studied for a wide array of psychological and physiological ailments. An exploration of stress physiology is an essential precursor to delineation of the mechanisms underlying the beneficial effects of meditation practices. Objective • The review outlines a model of interconnected physiological processes that might support the continued inclusion and expansion of meditation in the treatment of diverse medical conditions and to investigate the role that gut microbiota may play in realizing well-being through meditation. Design • The authors conducted a scientific literature database search with the goal of reviewing the link between stress management techniques and human microbiota. Their goal was also to identify the extent of underlying epigenetic reactions in these processes. The review was completed in approximately 2 y. Databases searched included Medline via PubMed and Ovid, PsycINFO via Ovid, Spinet, ProQuest Central, SAGE Research Methods Online, CINAHL Plus with Full Text, Science Direct, Springer Link, and Wiley Online Library. Keywords searched included, but were not limited to, stress, meditation, mindfulness, immune system, HPA axis, sympathetic nervous system, parasympathetic nervous system, microbiota, microbiome, gut-barrier function, leaky gut, vagus nerve, psychoneuroimmunology, epigenetic, and NF-κB. Setting • The study took place at New York University (New York, NY, USA), the University of California, San Diego (La Jolla, CA, USA), and the Chopra Foundation (Carlsbad, CA, USA). Results • Psychological stress typically triggers a fight-or-flight response, prompting corticotropin-releasing hormone and catecholamine production in various parts of the body, which ultimately disturbs the microbiota. In the absence of stress, a healthy microbiota produces short-chain fatty acids that exert anti-inflammatory and antitumor effects. During stress, an altered gut microbial population affects the regulation of neurotransmitters mediated by the microbiome and gut barrier function. Meditation helps regulate the stress response, thereby suppressing chronic inflammation states and maintaining a healthy gut-barrier function. Conclusions • The current research team recommends the integration of meditation into conventional health care and wellness models. Concurrently, studies to explore the effects of meditation on human microbiota are warranted.

Identification of Altered Metabolomic Profiles Following a Panchakarma-based Ayurvedic Intervention in Healthy Subjects: The Self-Directed Biological Transformation Initiative (SBTI).

The effects of integrative medicine practices such as meditation and Ayurveda on human physiology are not fully understood. The aim of this study was to identify altered metabolomic profiles following an Ayurveda-based intervention. In the experimental group, 65 healthy male and female subjects participated in a 6-day Panchakarma-based Ayurvedic intervention which included herbs, vegetarian diet, meditation, yoga, and massage. A set of 12 plasma phosphatidylcholines decreased (adjusted p < 0.01) post-intervention in the experimental (n = 65) compared to control group (n = 54) after Bonferroni correction for multiple testing; within these compounds, the phosphatidylcholine with the greatest decrease in abundance was PC ae C36:4 (delta = -0.34). Application of a 10% FDR revealed an additional 57 metabolites that were differentially abundant between groups. Pathway analysis suggests that the intervention results in changes in metabolites across many pathways such as phospholipid biosynthesis, choline metabolism, and lipoprotein metabolism. The observed plasma metabolomic alterations may reflect a Panchakarma-induced modulation of metabotypes. Panchakarma promoted statistically significant changes in plasma levels of phosphatidylcholines, sphingomyelins and others in just 6 days. Forthcoming studies that integrate metabolomics with genomic, microbiome and physiological parameters may facilitate a broader systems-level understanding and mechanistic insights into these integrative practices that are employed to promote health and well-being.