A Gentleman's Agreement

Another article about the gut microbiota and immunity is here.  Abstract:

Our body is colonized by more than a hundred trillion commensals, represented by viruses, bacteria and fungi. This complex interaction has shown that the microbiome system contributes to the host's adaptation to its environment, providing genes and functionality that give flexibility of diet and modulate the immune system in order not to reject these symbionts. In the intestine, specifically, the microbiota helps developing organ structures, participates of the metabolism of nutrients and induces immunity. Certain components of the microbiota have been shown to trigger inflammatory responses, whereas others, anti-inflammatory responses. The diversity and the composition of the microbiota, thus, play a key role in the maintenance of intestinal homeostasis and explain partially the link between intestinal microbiota changes and gut-related disorders in humans. Tight junction proteins are key molecules for determination of the paracellular permeability. In the context of intestinal inflammatory diseases, the intestinal barrier is compromised, and decreased expression and differential distribution of tight junction proteins is observed. It is still unclear what is the nature of the luminal or mucosal factors that affect the tight junction proteins function, but the modulation of the immune cells found in the intestinal lamina propria is hypothesized as having a role in this modulation. In this review, we provide an overview of the current understanding of the interaction of the gut microbiota with the immune system in the development and maintenance of the intestinal barrier.

Immunity and maintenance of the intestinal barrier - crucial to health - are strongly affected by the composition of the gut microbiota, which in turn is strongly affected by diet.  High fiber, active culture yogurt - these are part of a healthy diet and can help maintain a better gut profile.

What We Eat Is What We Think?

Consider that diet can affect your gut microbiome.  Consider also that gut bacteria produce short chain fatty acids from dietary fiber, so that diet can not only affect what bacterial species are in the gut but what products they produce.  Now, take a look at this article on the “gut-brain axis” mediated in part by lipids, including fatty acids, and this other article on a similar topic.

“We are what we eat,” indeed.  Perhaps, we “think what we eat” as well.

Elimination Diets For Neurodevelopmental Disorders.

Elimination diets attempt to identity foods that cause certain symptoms or disorders.  Here is a paper that focuses on elimination diets as interventions for, e.g., attention deficit hyperactivity disorder and autism spectrum disorder.  Abstract:

Nutrition plays an important role in neurodevelopment. This insight has led to increasing research into the efficacy of nutrition-related interventions for treating neurodevelopmental disorders. This review discusses an elimination diet as a treatment for attention deficit hyperactivity disorder and autism spectrum disorder, with a focus on the efficacy of the food additives exclusion diet, gluten-free/casein-free diet and oligoantigenic diet. Furthermore, we discuss the potential mechanisms of elimination diets' effects in these neurodevelopmental disorders. The main candidate mechanism is the microbiome-gut-brain axis possibly involving complex interactions between multiple systems, including the metabolic, immune, endocrine, and neural system. We conclude with practical implications and future directions into the investigation of an elimination diet's efficacy in the treatment of attention deficit hyperactivity disorder and autism spectrum disorder.

Once again we see the power of nutrition and diet to affect serious human health and developmental problems, and we note the mention of "the microbiome-gut-brain axis" - demonstrating, also once again, the relevance of the gut microbiome to various aspects of human well-being.

Negative Effects Of Dietary Fiber Deficiency

Another role for dietary fiber shown here, abstract:

Despite the accepted health benefits of consuming dietary fiber, little is known about the mechanisms by which fiber deprivation impacts the gut microbiota and alters disease risk. Using a gnotobiotic mouse model, in which animals were colonized with a synthetic human gut microbiota composed of fully sequenced commensal bacteria, we elucidated the functional interactions between dietary fiber, the gut microbiota, and the colonic mucus barrier, which serves as a primary defense against enteric pathogens. We show that during chronic or intermittent dietary fiber deficiency, the gut microbiota resorts to host-secreted mucus glycoproteins as a nutrient source, leading to erosion of the colonic mucus barrier. Dietary fiber deprivation, together with a fiber-deprived, mucus-eroding microbiota, promotes greater epithelial access and lethal colitis by the mucosal pathogen, Citrobacter rodentium. Our work reveals intricate pathways linking diet, the gut microbiome, and intestinal barrier dysfunction, which could be exploited to improve health using dietary therapeutics.

Dietary fiber can have many beneficial effects, including the production of short chain fatty acids that are good for colonic health and of course fiber helps with bowel movements to avoid constipation.  This mouse study shows that when there is a deficiency of dietary fiber, the gut microbiota that would normally digest fiber will instead start using the gut mucus as an energy source, eroding the protective lining on the colon and allowing pathogenic organisms to have access.

Eat your fiber!

Vitamin D Against Colon Cancer

Roles of vitamin D in colon cancer prevention, abstract:

Colorectal cancer (CRC) is the neoplasia that is most frequently associated with vitamin D deficiency in epidemiological and observational studies in terms of incidence and mortality. Many mechanistic studies show that the active vitamin D metabolite (1α,25-dihydroxyvitamin D3 or calcitriol) inhibits proliferation and promotes epithelial differentiation of human colon carcinoma cell lines that express vitamin D receptor (VDR) via the regulation of a high number of genes. A key action underlining this effect is the multilevel inhibition of the Wnt/β-catenin signaling pathway, whose abnormal activation in colon epithelial cells initiates and promotes CRC. Recently, our group has shown that calcitriol modulates gene expression and inhibits protumoral properties of patient-derived colon cancer-associated fibroblasts (CAFs). Accordingly, high VDR expression in tumor stromal fibroblasts is associated with longer survival of CRC patients. Moreover, many types of immune cells express VDR and are regulated by calcitriol, which probably contributes to its action against CRC. Given the role attributed to the intestinal microbiota in CRC and the finding that it is altered by vitamin D deficiency, an indirect antitumoral effect of calcitriol is also plausible at this level. In summary, calcitriol has an array of potential protective effects against CRC by acting on carcinoma cells, CAFs, immune cells and probably also the gut microbiota.

Fiber And Microbiota

Dietary fiber can increase levels of certain gut microbiota bacterial species, as well as higher levels of butyrate, a short chain fatty acid with beneficial anti-cancer effects in the colon.  Abstract:

BACKGROUND:

Dysfunction of the gut microbiota is frequently reported as a manifestation of chronic diseases, and therefore presents as a modifiable risk factor in their development. Diet is a major regulator of the gut microbiota and certain types of dietary fiber may modify bacterial numbers and metabolism, including short-chain fatty acid (SCFA) generation.

OBJECTIVE:

A systematic review and meta-analysis were undertaken to assess the effect of dietary fiber interventions on gut microbiota composition in healthy adults.

DESIGN:

A systematic search was conducted across MEDLINE, EMBASE, CENTRAL, and CINAHL for randomized controlled trials using culture and/or molecular microbiological techniques evaluating the effect of fiber intervention on gut microbiota composition in healthy adults. Meta-analyses via a random-effects model were performed on alpha diversity, prespecified bacterial abundances including Bifidobacterium and Lactobacillus spp., and fecal SCFA concentrations comparing dietary fiber interventions with placebo/low-fiber comparators.

RESULTS:

A total of 64 studies involving 2099 participants were included. Dietary fiber intervention resulted in higher abundance of Bifidobacterium spp. [standardized mean difference (SMD) 0.64 (95% CI: 0.42, 0.86); P < 0.00001)] and Lactobacillus spp. [SMD: 0.22 (0.03, 0.41), P = 0.02] as well as fecal butyrate concentration [SMD: 0.24 (0.00, 0.47), P = 0.05] compared with placebo/low-fiber comparators. Subgroup analysis revealed that fructans and galacto-oligosaccharides led to significantly greater abundance of both Bifidobacterium spp. and Lactobacillus spp. compared with comparators (P < 0.00001 and P = 0.002, respectively). No differences in effect were found between fiber intervention and comparators for α-diversity, abundances of other prespecified bacteria, or other SCFA concentrations.

CONCLUSIONS:

Dietary fiber intervention, particularly involving fructans and galacto-oligosaccharides, leads to higher fecal abundance of Bifidobacterium and Lactobacillus spp. but does not affect α-diversity. Further research is required to better understand the role of individual fiber types on the growth of microbes and the overall gut microbial community. This review was registered at PROSPERO as CRD42016053101.

Wild Mice And Microbiota

Wild mice have different gut microbiota than lab mice and giving the lab mice the natural microbiota of the wild mice enhanced the health of the lab mice. There is much significance here, including the importance of the microbiota for health and fitness.  Abstract:

Laboratory mice, while paramount for understanding basic biological phenomena, are limited in modeling complex diseases of humans and other free-living mammals. Because the microbiome is a major factor in mammalian physiology, we aimed to identify a naturally evolved reference microbiome to better recapitulate physiological phenomena relevant in the natural world outside the laboratory. Among 21 distinct mouse populations worldwide, we identified a closely related wild relative to standard laboratory mouse strains. Its bacterial gut microbiome differed significantly from its laboratory mouse counterpart and was transferred to and maintained in laboratory mice over several generations. Laboratory mice reconstituted with natural microbiota exhibited reduced inflammation and increased survival following influenza virus infection and improved resistance against mutagen/inflammation-induced colorectal tumorigenesis. By demonstrating the host fitness-promoting traits of natural microbiota, our findings should enable the discovery of protective mechanisms relevant in the natural world and improve the modeling of complex diseases of free-living mammals.

Skin Microbiome Review

A review of the skin microbiome, with information on relevant dermatological disorders, including acne is here.  One can expect the skin microbiome, like the gut microbiome, to be linked to an increasingly diverse array of human health conditions. Abstract:

Functioning as the exterior interface of the human body with the environment, skin acts as a physical barrier to prevent the invasion of foreign pathogens while providing a home to the commensal microbiota. The harsh physical landscape of skin, particularly the desiccated, nutrient-poor, acidic environment, also contributes to the adversity that pathogens face when colonizing human skin. Despite this, the skin is colonized by a diverse microbiota. In this Review, we describe amplicon and shotgun metagenomic DNA sequencing studies that have been used to assess the taxonomic diversity of microorganisms that are associated with skin from the kingdom to the strain level. We discuss recent insights into skin microbial communities, including their composition in health and disease, the dynamics between species and interactions with the immune system, with a focus on Propionibacterium acnes, Staphylococcus epidermidis and Staphylococcus aureus.

Microbiota, Diet, And Blood Pressure

Response to diet – for example, for blood pressure – is influenced by the microbiota, just as s much else is.  Abstract:

BACKGROUND:

Interindividual variation in the response to diet is common, but the underlying mechanism for such variation is unclear.

OBJECTIVE:

The objective of this study was to use a metabolic profiling approach to identify a panel of urinary metabolites representing individuals demonstrating typical (homogeneous) metabolic responses to healthy diets, and subsequently to define the association of these metabolites with improvement of risk factors for cardiovascular diseases (CVDs).

DESIGN:

24-h urine samples from 158 participants with pre-hypertension and stage 1 hypertension, collected at baseline and following the consumption of a carbohydrate-rich, a protein-rich, and a monounsaturated fat-rich healthy diet (6 wk/diet) in a randomized, crossover study, were analyzed by proton (1H) nuclear magnetic resonance (NMR) spectroscopy. Urinary metabolite profiles were interrogated to identify typical and variable responses to each diet. We quantified the differences in absolute excretion of metabolites, distinguishing between dietary comparisons within the typical response groups, and established their associations with CVD risk factors using linear regression.

RESULTS:

Globally all 3 diets induced a similar pattern of change in the urinary metabolic profiles for the majority of participants (60.1%). Diet-dependent metabolic variation was not significantly associated with total cholesterol or low density lipoprotein (LDL) cholesterol concentrations. However, blood pressure (BP) was found to be significantly associated with 6 urinary metabolites reflecting dietary intake [proline-betaine (inverse), carnitine (direct)], gut microbial co-metabolites [hippurate (direct), 4-cresyl sulfate (inverse), phenylacetylglutamine (inverse)], and tryptophan metabolism [N-methyl-2-pyridone-5-carboxamide (inverse)]. A dampened clinical response was observed in some individuals with variable metabolic responses, which could be attributed to nonadherence to diet (≤25.3%), variation in gut microbiome activity (7.6%), or a combination of both (7.0%).

CONCLUSIONS:

These data indicate interindividual variations in BP in response to dietary change and highlight the potential influence of the gut microbiome in mediating this relation. This approach provides a framework for stratification of individuals undergoing dietary management. The original OmniHeart intervention study and the metabolomics study were registered at www.clinicaltrials.gov as NCT00051350 and NCT03369535, respectively

Determinants Of The Microbiome

Environmental effects are more important than genetic for determining the microbiome, strongly suggesting the malleability of the microbiome, which can influence human health.  Abstract:

Human gut microbiome composition is shaped by multiple factors but the relative contribution of host genetics remains elusive. Here we examine genotype and microbiome data from 1,046 healthy individuals with several distinct ancestral origins who share a relatively common environment, and demonstrate that the gut microbiome is not significantly associated with genetic ancestry, and that host genetics have a minor role in determining microbiome composition. We show that, by contrast, there are significant similarities in the compositions of the microbiomes of genetically unrelated individuals who share a household, and that over 20% of the inter-person microbiome variability is associated with factors related to diet, drugs and anthropometric measurements. We further demonstrate that microbiome data significantly improve the prediction accuracy for many human traits, such as glucose and obesity measures, compared to models that use only host genetic and environmental data. These results suggest that microbiome alterations aimed at improving clinical outcomes may be carried out across diverse genetic backgrounds.

You (including your microbiome) are what you eat.

Colorectal Cancer And Bacterial Colonization

Colonization by a specific bacterial species is “strongly associated” with colorectal cancer; whether this is cause or effect – or both – remains to fully determined.  This study suggests that it is at least effect – conditions leading to cancer development, including deregulation of Wnt signaling, favor the colonization at the expense of other bacterial species.  It is of course also possible that these “bad” (?) bacteria, once established, then affect the further progression of the cancer.  At the very least, their presence is a sign something is not right.  Abstract:

Colonization by Streptococcus gallolyticus subsp. gallolyticus (SGG) is strongly associated with the occurrence of colorectal cancer (CRC). However, the factors leading to its successful colonization are unknown, and whether SGG influences the oncogenic process or benefits from the tumor-prone environment to prevail remains an open question. Here, we elucidate crucial steps that explain how CRC favors SGG colonization. By using mice genetically prone to CRC, we show that SGG colonization is 1,000-fold higher in tumor-bearing mice than in normal mice. This selective advantage occurs at the expense of resident intestinal enterococci. An SGG-specific locus encoding a bacteriocin ("gallocin") is shown to kill enterococci in vitro. Importantly, bile acids strongly enhance this bacteriocin activity in vivo, leading to greater SGG colonization. Constitutive activation of the Wnt pathway, one of the earliest signaling alterations in CRC, and the decreased expression of the bile acid apical transporter gene Slc10A2, as an effect of the Apc founding mutation, may thereby sustain intestinal colonization by SGG. We conclude that CRC-specific conditions promote SGG colonization of the gut by replacing commensal enterococci in their niche.

We Are Human Holobionts

We are” holobionts” – combination of our own cells and the microbes who live on and in our bodies, and there are evolving combinations of these over a lifetime.  Abstract:

The "holobiont" concept, defined as the collective contribution of the eukaryotic and prokaryotic counterparts to the multicellular organism, introduces a complex definition of individuality enabling a new comprehensive view of human evolution and personalized characteristics. Here, we provide snapshots of the evolving microbial-host associations and relations during distinct milestones across the lifespan of a human being. We discuss the current knowledge of biological symbiosis between the microbiome and its host and portray the challenges in understanding these interactions and their potential effects on human physiology, including microbiome-nervous system inter-relationship and its relevance to human variation and individuality.

Microbial Metabolites Against Multiple Sclerosis?

More possible benefits for modulating the microbiome; abstract:

Microglia and astrocytes modulate inflammation and neurodegeneration in the central nervous system (CNS)1-3. Microglia modulate pro-inflammatory and neurotoxic activities in astrocytes, but the mechanisms involved are not completely understood4,5. Here we report that TGFα and VEGF-B produced by microglia regulate the pathogenic activities of astrocytes in the experimental autoimmune encephalomyelitis (EAE) mouse model of multiple sclerosis. Microglia-derived TGFα acts via the ErbB1 receptor in astrocytes to limit their pathogenic activities and EAE development. Conversely, microglial VEGF-B triggers FLT-1 signalling in astrocytes and worsens EAE. VEGF-B and TGFα also participate in the microglial control of human astrocytes. Furthermore, expression of TGFα and VEGF-B in CD14+ cells correlates with the multiple sclerosis lesion stage. Finally, metabolites of dietary tryptophan produced by the commensal flora control microglial activation and TGFα and VEGF-B production, modulating the transcriptional program of astrocytes and CNS inflammation through a mechanism mediated by the aryl hydrocarbon receptor. In summary, we identified positive and negative regulators that mediate the microglial control of astrocytes. Moreover, these findings define a pathway through which microbial metabolites limit pathogenic activities of microglia and astrocytes, and suppress CNS inflammation. This pathway may guide new therapies for multiple sclerosis and other neurological disorders.

Preventing Neuronal Disease Through The Microbiota

Once again, modifying the microbiota through diet can prevent neuroimmune and neuroinflammatory disease.

The gut-brain-axis refers to the bidirectional communication between the enteric nervous system and the central nervous system. Mounting evidence supports the premise that the intestinal microbiota plays a pivotal role in its function and has led to the more common and perhaps more accurate term gut-microbiota-brain axis. Numerous studies have identified associations between an altered microbiome and neuroimmune and neuroinflammatory diseases. In most cases, it is unknown if these associations are cause or effect; notwithstanding, maintaining or restoring homeostasis of the microbiota may represent future opportunities when treating or preventing these diseases. In recent years, several studies have identified the diet as a primary contributing factor in shaping the composition of the gut microbiota, and in turn, the mucosal and systemic immune systems. In this review, we will discuss the potential opportunities and challenges with respect to modifying and shaping the microbiota through diet and nutrition in order to treat or prevent neuroimmune and neuroinflammatory disease.

The Appendix and IBD

Take home points: The appendix most likely is not just a “vestigial remnant” but may play a role as a “microbiota reservoir.”  Also, the appendix may play a role in inflammatory bowel disease, particularly ulcerative colitis, and for some of these patients, an appendectomy may be helpful.  Abstract:

The human appendix has long been considered as a vestigial organ, an organ that has lost its function during evolution. In recent years, however, reports have emerged that link the appendix to numerous immunological functions in humans. Evidence has been presented for an important role of the appendix in maintaining intestinal health. This theory suggests that the appendix may be a reservoir or 'safe house' from which the commensal gut flora can rapidly be reestablished if it is eradicated from the colon. However, the appendix may also have a role in the development of inflammatory bowel disease (IBD). Several large epidemiological cohort studies have demonstrated the preventive effect of appendectomy on the development of ulcerative colitis, a finding that has been confirmed in murine colitis models. In addition, current studies are examining the possible therapeutic effect of an appendectomy to modulate disease course in patients with ulcerative colitis. This literature review assesses the current knowledge about the clinical and immunological aspects of the vermiform appendix in IBD and suggests that the idea of the appendix as a vestigial remnant should be discarded.

Colon Cancer Mutations Associated With The Gut Microbiota

An extremely important study on colon cancer concludes: “We found statistically significant associations between loss-of-function mutations in tumor genes and shifts in the abundances of specific sets of bacterial taxa, suggestive of potential functional interaction.”  Further, the correlation between bacterial types and tumor mutations allowed for predictions about interactions between the mutations and the downstream signaling pathways affected by these mutations.  One can expect future work to more clearly delineate the molecular mechanisms of interaction between the microbiota and cancer mutations.  In the meantime, once again – for the thousandth time it seems – the importance of the gut microbiota is emphasized.  Abstract:

Variation in the gut microbiome has been linked to colorectal cancer (CRC), as well as to host genetic variation. However, we do not know whether, in addition to baseline host genetics, somatic mutational profiles in CRC tumors interact with the surrounding tumor microbiome, and if so, whether these changes can be used to understand microbe-host interactions with potential functional biological relevance. Here, we characterized the association between CRC microbial communities and tumor mutations using microbiome profiling and whole-exome sequencing in 44 pairs of tumors and matched normal tissues. We found statistically significant associations between loss-of-function mutations in tumor genes and shifts in the abundances of specific sets of bacterial taxa, suggestive of potential functional interaction. This correlation allows us to statistically predict interactions between loss-of-function tumor mutations in cancer-related genes and pathways, including MAPK and Wnt signaling, solely based on the composition of the microbiome. In conclusion, our study shows that CRC microbiomes are correlated with tumor mutational profiles, pointing towards possible mechanisms of molecular interaction.

More On Gut Microbiota And Colorectal Cancer

Another paper about gut microbiota and colorectal cancer is of interest.  Abstract:

Pre-clinical and clinical data produce mounting evidence that the microbiota is strongly associated with colorectal carcinogenesis. Dysbiosis may change the course of carcinogenesis as microbial actions seem to impact genetic and epigenetic alterations leading to dysplasia, clonal expansion and malignant transformation. Initiation and promotion of colorectal cancer may result from direct bacterial actions, bacterial metabolites and inflammatory pathways. Newer aspects of microbiota and colorectal cancer include quorum sensing, biofilm formation, sidedness and effects/countereffects of microbiota and probiotics on chemotherapy. In the future, targeting the microbiota will probably be a powerful weapon in the battle against CRC as gut microbiology, genomics and metabolomics promise to uncover important linkages between microbiota and intestinal health.

Again we see the paradigm that targeting the gut microbiota, to yield a more healthy bacterial profile,c can be a future anti-cancer approach.

Cancer Immunotherapy: The Systemic Response

An article  on cancer immunotherapy; the abstract:

Immune responses involve coordination across cell types and tissues. However, studies in cancer immunotherapy have focused heavily on local immune responses in the tumor microenvironment. To investigate immune activity more broadly, we performed an organism-wide study in genetically engineered cancer models using mass cytometry. We analyzed immune responses in several tissues after immunotherapy by developing intuitive models for visualizing single-cell data with statistical inference. Immune activation was evident in the tumor and systemically shortly after effective therapy was administered. However, during tumor rejection, only peripheral immune cells sustained their proliferation. This systemic response was coordinated across tissues and required for tumor eradication in several immunotherapy models. An emergent population of peripheral CD4 T cells conferred protection against new tumors and was significantly expanded in patients responding to immunotherapy. These studies demonstrate the critical impact of systemic immune responses that drive tumor rejection.

In other words, a local response at the tumor by the immune system is sufficient for sustained proliferation of the immune response required for tumor rejection.  A (body-wide) systemic immune response is required, a set of responses that, as the article states "involve coordination across cell types and tissues."

It would stand to reason, as my hypothesis, that those things that would enhance the overall function of the immune system - diet, exercise, proper sleep,  less stress, and possibly the gut microbiota - would assist the body in generating the systemic responses required for tumor rejection.  More studies are required to evaluate my hypothesis.

Breast Cancer Microbiota

New discoveries are demonstrating the importance of tumor microbiota: bacteria associated with particular cancers. Here is a paper concerned with the breast cancer microbiota, and shows that certain species of bacteria found in breast cancer tissue and surrounding microenvironment contribute to gene expression that influences cancer progression. The microbiota-cancer link will continue to provide new findings that could impact therapeutics.  Perhaps antibiotics could be part of the toolkit?  Abstract:

The inflammatory tumoral-immune response alters the physiology of the tumor microenvironment, which may attenuate genomic instability. In addition to inducing inflammatory immune responses, several pathogenic bacteria produce genotoxins. However the extent of microbial contribution to the tumor microenvironment biology remains unknown. We utilized The Cancer Genome Atlas, (TCGA) breast cancer data to perform a novel experiment utilizing unmapped and mapped RNA sequencing read evidence to minimize laboratory costs and effort. Our objective was to characterize the microbiota and associate the microbiota with the tumor expression profiles, for 668 breast tumor tissues and 72 non-cancerous adjacent tissues. The prominent presence of Proteobacteria was increased in the tumor tissues and conversely Actinobacteria abundance increase in non-cancerous adjacent tissues. Further, geneset enrichment suggests Listeria spp to be associated with the expression profiles of genes involved with epithelial to mesenchymal transitions. Moreover, evidence suggests H. influenza may reside in the surrounding stromal material and was significantly associated with the proliferative pathways: G2M checkpoint, E2F transcription factors, and mitotic spindle assembly. In summary, further unraveling this complicated interplay should enable us to better diagnose and treat breast cancer patients.

Mental States, The Immine System, And the Gut Microbiome

Mental states can affect the gut microbiome, with downstream effects on the immune system and cancer risk. Stress alters these factors in the negative direction, while meditation changes direction positively, particularly with an optimal microbiome and suppressed inflammation.  The mind-body axis seems to revolve around the gut microbiome, and there is much potential for preventive and therapeutic interventions that include reduced stress and meditation as well as more traditional pharmacological therapeutics. Abstract:

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.