Beyond the gut: decoding the gut–immune–brain axis in health and disease

Role of the Gut in Visceral Fat Inflammation and Metabolic Disorders

Reshaping the gut microbiota: Tangliping decoction and its core blood-absorbed component quercetin improve diabetic cognitive impairment.

The human body is full of an extensive number of commensal microbes, consisting of bacteria, viruses, and fungi, collectively termed the human microbiome. The initial acquisition of microbiota occurs from both the external and maternal environments, and the vast majority of them colonize the gastrointestinal tract (GIT). These microbial communities play a central role in the maturation and development of the immune system, the central nervous system, and the GIT system and are also responsible for essential metabolic pathways. Various factors, including host genetic predisposition, environmental factors, lifestyle, diet, antibiotic or nonantibiotic drug use, etc., affect the composition of the gut microbiota. Recent publications have highlighted that an imbalance in the gut microflora, known as dysbiosis, is associated with the onset and progression of neurological disorders. Moreover, characterization of the microbiome-host cross talk pathways provides insight into novel therapeutic strategies. Novel preclinical and clinical research on interventions related to the gut microbiome for treating neurological conditions, including autism spectrum disorders, Parkinson's disease, schizophrenia, multiple sclerosis, Alzheimer's disease, epilepsy, and stroke, hold significant promise. This review aims to present a comprehensive overview of the potential involvement of the human gut microbiome in the pathogenesis of neurological disorders, with a particular emphasis on the potential of microbe-based therapies and/or diagnostic microbial biomarkers. This review also discusses the potential health benefits of the administration of probiotics, prebiotics, postbiotics, and synbiotics and fecal microbiota transplantation in neurological disorders.

Unhealthy gut, unhealthy brain: The role of the intestinal microbiota in neurodegenerative diseases

What Is Your Gut Telling You? Exploring the Role of the Microbiome in Gut-Brain Signaling.

2021 Workshop: Neurodegenerative Diseases in the Gut-Brain Axis—Parkinson's Disease

Probiotics restore impaired spatial cognition and synaptic plasticity of prenatally-stressed male rats: focus on hippocampal and intestinal tight junctions.

BackgroundCoronary artery disease (CAD) is a widespread heart condition caused by atherosclerosis and influences millions of people worldwide. Early detection of CAD is challenging due to the lack of specific biomarkers. The gut microbiota and host-microbiota interactions have been well documented to affect human health. However, investigation that reveals the role of gut microbes in CAD is still limited. This study aims to uncover the synergistic effects of host genes and gut microbes associated with CAD through integrative genomic analyses.ResultsHerein, we collected 52 fecal and 50 blood samples from CAD patients and matched controls, and performed amplicon and transcriptomic sequencing on these samples, respectively. By comparing CAD patients with health controls, we found that dysregulated gut microbes were significantly associated with CAD. By leveraging the Random Forest method, we found that combining 20 bacteria and 30 gene biomarkers could distinguish CAD patients from health controls with a high performance (AUC = 0.92). We observed that there existed prominent associations of gut microbes with several clinical indices relevant to heart functions. Integration analysis revealed that CAD-relevant gut microbe genus Fusicatenibacter was associated with expression of CAD-risk genes, such as GBP2, MLKL, and CPR65, which is in line with previous evidence (Tang et al., Nat Rev Cardiol 16:137-154, 2019; Kummen et al., J Am Coll Cardiol 71:1184-1186, 2018). In addition, the upregulation of immune-related pathways in CAD patients were identified to be primarily associated with higher abundance of genus Blautia, Eubacterium, Fusicatenibacter, and Monoglobus.ConclusionsOur results highlight that dysregulated gut microbes contribute risk to CAD by interacting with host genes. These identified microbes and interacted risk genes may have high potentials as biomarkers for CAD.

The discovery of the size and complexity of the human microbiome has resulted in an ongoing reevaluation of many concepts of health and disease, including diseases affecting the CNS. A growing body of preclinical literature has demonstrated bidirectional signaling between the brain and the gut microbiome, involving multiple neurocrine and endocrine signaling mechanisms. While psychological and physical stressors can affect the composition and metabolic activity of the gut microbiota, experimental changes to the gut microbiome can affect emotional behavior and related brain systems. These findings have resulted in speculation that alterations in the gut microbiome may play a pathophysiological role in human brain diseases, including autism spectrum disorder, anxiety, depression, and chronic pain. Ongoing large-scale population-based studies of the gut microbiome and brain imaging studies looking at the effect of gut microbiome modulation on brain responses to emotion-related stimuli are seeking to validate these speculations. This article is a summary of emerging topics covered in a symposium and is not meant to be a comprehensive review of the subject.

This study aims to investigate whether human milk exosomes from gestational diabetes mellitus (GDM-EXO) and healthy (HEA-EXO) parturients differ in regulating intestinal development in offspring. The differential miRNAs associated with intestinal development in GDM-EXO and HEA-EXO were verified by using qPCR and their relationships with gut microbiota (GM) in infants were analyzed. C57BL/6J mice were gavaged with 50mg/kg·BW HEA-EXO or GDM-EXO. The intestinal morphology, gut barriers, ZO-1 and Occludin, and GM were determined by histological staining, Western blotting, and 16S rDNA amplicon sequencing, respectively. Hsa-miR-19b-3p, hsa-miR-148a-3p, and hsa-miR-320a-3p were upregulated, and hsa-miR-429 was decreased in GDM-EXO compared to HEA-EXO. The GDM parturients' infants had increased intestinal Coriobacteriaceae, Clostridiaceae, Erysipelotrichaceae, Erysipelatoclostridiaceae, and fewer Lactobacillaceae than the healthy parturient's infants. The four differential miRNAs in GDM-EXO all correlated with the infants' GM. GDM-EXO- and HEA-EXO-fed mice had greater villus lengths, villus length-to-crypt depth ratios, goblet cell numbers, elevated ZO-1 and Occludin, and lower crypt depths than control mice. HEA-EXO-fed mice had better intestinal morphology and gut barrier integrity than GDM-EXO-fed mice. GDM-EXO-fed mice had significantly decreased Lachnospiraceae and Oscillospiraceae than HEA-EXO-fed mice. GDM-EXO demonstrate weaker ability to promote intestinal development in offspring than HEA-EXO.

Repeated Social Defeat Stress Induces an Inflammatory Gut Milieu by Altering the Mucosal Barrier Integrity and Gut Microbiota Homeostasis

The human gastrointestinal tract harbors a complex and dynamic population of micro-organisms known as 'gut microbiota'. The gut micro-organisms exert great influence on us during the states of metabolic/immunological homeostasis as well as manifestation of or protection from diseases. Relative composition of gut microbiota is now known to be influenced by the type of diet, geographic locations and nutritional status of the individuals. Gut microbiota most closely interact with the gastrointestinal tract, liver, skin and central nervous system and hence, aid in physiological functions such as digestion and absorption of nutrients, neuro-transmission, fat metabolism, and immune responses. Accordingly, disturbance in the gut microflora architecture normally lead to several health disorders like obesity, diabetes, hypertension, rheumatoid arthritis, inflammatory bowel disease, nervous depression, anxiety, cognitive decline, Parkinson's Disease etc. The metagenomic studies of human gut flora have suggested that the bulk of the microbial community is made up of nine bacteriophyta namely: Firmicutes, Bacteroidetes, Proteobacteria, Actinobacteria, Fusobacteria, Verrucomicrobia, Cyanobacteria and Spirochaetes. Several studies have also indicated a positive association of gut microbes with bidirectional regulation of intestinal and central nervous system (CNS) through neurotransmitter, endocrine, immune and metabolic pathways. An imbalanced gut microbiota has been shown to affect the progression of CNS diseases, including cerebral ischemia, Alzheimer's disease, disseminated sclerosis and hepatic encephalopathy. In addition, gut microbiota imbalance can also increase intestinal permeability that can lead to liver toxicity and several other pathophysiological complications. Intestinal microbiota contributes to diverse mammalian processes including the metabolic function of the drugs, both traditional as well as modern. A large number of herbal medicines have been found to act in association with gut microbiota because majority of herbal drugs are orally administered and invariably come in direct contact with these microbes. Since most herbal preparations are made up of a large number of plant-derived bioactive metabolites, their precise mode of actions on gut flora, body metabolism and disease management/treatment is often not fully explained. Recent developments in the field of gut metagenomics vis-à-vis bioavailability of herbal ingredients and their pharmacodynamics in disease conditions are providing fresh insights to these associations. Today a general consensus is that most traditional herbals treat disease by three primary modes: getting metabolized into more pharmacologically active metabolites by the action of gut microbiota; regulating the gut microbiota balance in terms of relative population of different bacteria particularly the Firmicutes-to-Bacteroidetes ratio (F/B); and by regulating the synthesis of fermentation products of the gut microbes such as acetate, butyrate and propionate etc. The gut micro-flora architecture and its association with herbal medicines is a hot topic of discussion today. In last five years >13000 papers were published on studies related to gut microbiota. This review is an attempt to summarize our current understanding of this subject with sole intention of sensitizing the researchers' community of medicinal and aromatic plant sciences in India to validate and valorize our existing AYUSH prescriptions in the context of gut microbiota influences for enhancing their global acceptance.

Background: Recent studies have shown extensive crosstalk between our immune system and gut microbiome (GM). The host immune system plays a vital role in the maintenance of GM homeostasis by 1) establishing a balance between eliminating invading pathogens and promoting the growth of beneficial microbes, 2) producing short-chain fatty acids (SCFA), the main source of nutrition for the colon cells, and 3) modulating the immune system by cytokine production. Mounting evidence shows that the GM of patients with high rates of infection are characterized by an imbalance of bacteria, inducing proinflammatory states and reduced capacity for SCFA synthesis. As chronic lymphocytic leukemia (CLL) is, among others, also characterized by high rate of infectious complications and an altered immune system, it is warranted to explore composition of the CLL microbiome. Aims: We aim to investigate the hypothesis that deviation of the GM from homeostasis, i.e. loss of ‘health promoting’ gut microbes and/or overgrowth of pathogenic bacteria, distinguishes patients with CLL from the background population. Methods: Feces samples of patients with CLL were collected, immediately fixated and frozen within 72 h; total genomic DNA was sequenced. Feces samples of healthy controls were chosen to match the CLL population with respect to age, demographic data, sample collection method, and sequencing platform. Taxonomical profiling was done using an in-house bioinformatics pipeline. Results: A total of 61 CLL patients and 30 healthy individuals were included in the study. We observed reduced GM alpha diversity, and depletion of bacterial members of Lachnospiraceae and Ruminococcaceae families among the CLL patients when compared to healthy individuals. Our data show that members of the Lachnospiraceae family (Anaerostipes hadrus, Coprococcus comes, Blautia spp., Dorea spp.), and 3 members of Ruminococcaeae family (Ruminococcus torques, Ruminococcus bromii, Faecalibacterium prausnitzii) were among the most differentially abundant bacterial species between the microbiomes of healthy individuals and CLL. Their mean proportions were shown to be significantly higher in healthy microbiome samples. As further differentially abundant species we observed Bacteroides sp. and Alistipes finegoldii, which both demonstrated significantly higher mean proportions in CLL microbiomes (Fig 1). Image:Summary/Conclusion: To sum up, the CLL microbiomes in comparison to healthy controls demonstrated lower enrichment of Lachnospiraceae and Ruminococcaceae families, the major SCFAs-producing bacterial taxa reported to have a protective effect against inflammation. This supports the notion that proinflammatory risk factors identified in other cohorts with GM dysbiosis are also present within CLL patients. As CLL represents an antigen driven malignancy with immune dysfunction, we hypothesize that GM dysbiosis could both be implicated in the pathogenesis of CLL, through antigenic drive, and contribute to the distortion of the immune system in CLL. Notably, both immune dysfunction and treatment (e.g. antimicrobials) may influence the CLL microbiome itself and therefore confound cross-sectional clinical studies. We therefore plan to investigate the interaction between microbiome and CLL development in the TCL1 mouse model of CLL. Also, identification of potential mechanistic links between the GM and the microenvironment in CLL should be investigated, e.g. extravesicular vesicles or cytokines released from or impacted by the GM. In addition, modulation of the microbiome in animal models may help to establish causal connections between the GM and CLL development.

Edgeworthia gardneri (Wall.) Meisn protects against HFD-induced murine atherosclerosis through improving gut microbiota-mediated intestinal barrier integrity.

Can we promote neural regeneration through microbiota-targeted strategies? Introducing the new concept of neurobiotics.