Seeking the Psilocybiome: Psychedelics meet the microbiota-gut-brain axis

Moving towards a systems psychiatry paradigm embraces the inherent complex interactions across all levels from micro to macro and necessitates an integrated approach to treatment. Cortical 5-HT2A receptors are key primary targets for the effects of serotonergic psychedelics. However, the therapeutic mechanisms underlying psychedelic therapy are complex and traverse molecular, cellular, and network levels, under the influence of biofeedback signals from the periphery and the environment. At the interface between the individual and the environment, the gut microbiome, via the gut-brain axis, plays an important role in the unconscious parallel processing systems regulating host neurophysiology. While psychedelic and microbial signalling systems operate over different timescales, the microbiota-gut-brain (MGB) axis, as a convergence hub between multiple biofeedback systems may play a role in the preparatory phase, the acute administration phase, and the integration phase of psychedelic therapy. In keeping with an interconnected systems-based approach, this review will discuss the gut microbiome and mycobiome and pathways of the MGB axis, and then explore the potential interaction between psychedelic therapy and the MGB axis and how this might influence mechanism of action and treatment response. Finally, we will discuss the possible implications for a precision medicine-based psychedelic therapy paradigm. (AU)

B Lymphocyte Development in the Bursa of Fabricius of Young Broilers is Influenced by the Gut Microbiota.

Chickens have been used as a valuable and traditional model for studies on basic immunology. B lymphocytes were first identified in the bursa of Fabricius (BF) of broilers. The microbiota is important for immune system development and function. However, the effect of the microbiota on mediating B cell development and its regulatory mechanism is poorly elucidated. Here, we show that the gut microbiota is associated with the development of bursal B cells in young chickens. Changing patterns of both the alpha diversity and the expression of the B cell marker Bu-1α in the gut microbiota were related to the ages of chickens at different growth phases. Further correlation analysis revealed the marked correlation between the relative abundances of Intestinimonas, Bilophila, Parasutterella, Bacteroides, Helicobacter, Campylobacter, and Mucispirillum and the expression of Bu-1α. In antibiotic-treated chickens, BF and B cell development had aberrations as the relative abundance of the microbiota in early life decreased. These findings were consistent with Spearman's correlation results. Single-cell transcriptome analysis indicated that the heterogeneity in the cellular composition and developmental trajectory of bursal B cells from antibiotic-treated chickens was large. We found a novel subpopulation of unnamed B cells and identified Taf1 as a new pivotal regulator of B cell lineage differentiation. Therefore, we provide novel insights into the regulatory role of the gut microbiota in B cell development in early life and the maturation of host humoral immunity. IMPORTANCE In this study, we used young broilers to investigate the relationship between their gut microbiota and bursal B cell development. We characterized the important variables, microbes, B cells, and immunoglobulins during the posthatch development of birds. We also identified several candidate taxa in the cecal contents associated with B cells. Our study provides a rich resource and cell-cell cross talk model supporting B cell differentiation from the bursa in vitro at single-cell resolution. Furthermore, we determined a new pivotal regulator (Taf1) of B cell differentiation. We believe that our study makes a significant contribution to the literature because our findings may elucidate the role of the gut microbiota in B cell differentiation. This study also serves as a basis for developing new strategies that modulate B cell differentiation to prevent diseases.

Characterization of Oral Microbiota Following Chemotherapy in Patients With Hematopoietic Malignancies.

Oral microbiota may be associated with serious local or systemic medical conditions resulting from chemotherapy. This study was conducted to evaluate the changes in the oral microbiota following the initiation of chemotherapy in patients with hematopoietic malignancies and to identify the characteristics of the oral microbiota associated with oral mucositis. Oral samples were collected from 57 patients with hematopoietic malignancies at 2 time points: before the start of chemotherapy and 8 to 20 days after the start of chemotherapy, when chemotherapy-induced oral mucositis often occurs, and 16S rRNA metagenomic analyses were performed. Comparative and linear discriminant analysis effect size (LEfSe) analyses were used to determine the characteristic bacterial groups before and after the initiation of chemotherapy and in those who developed oral mucositis. The alpha and beta diversities of oral microbiota before and after the initiation of chemotherapy differed significantly (operational taxonomic unit index, P < .001; Shannon's index, P < .001; unweighted UniFrac distances, P = .001; and weighted UniFrac distances, P = .001). The LEfSe analysis revealed a group of bacteria whose abundance differed significantly before and after the initiation of chemotherapy. In the group of patients who developed oral mucositis, a characteristic group of bacteria was identified before the start of chemotherapy. In conclusion, we characterized the oral microbiota associated with the initiation of chemotherapy in patients with hematopoietic malignancies. In addition, our findings suggest that oral microbiota composition before the start of chemotherapy may be associated with oral mucositis. The results of this study emphasize the importance of oral management focusing on the oral microbiota during chemotherapy in patients with hematologic malignancies.

The role of gut microbiota in T cell immunity and immune mediated disorders.

Gut microbiota was only considered as a commensal organism that aids in digestion, but recent studies revealed that the microbiome play a critical role in both physiological and pathological immune system. The gut microbiome composition is altered by environmental factors such as diet and hygiene, and the alteration affects immune cells, especially T cells. Advanced genomic techniques in microbiome research defined that specific microbes regulate T cell responses and the pathogenesis of immune-mediated disorders. Here, we review features of specific microbes-T cell crosstalk and relationship between the microbes and immunopathogenesis of diseases including in cancers, autoimmune disorders and allergic inflammations. We also discuss the limitations of current experimental animal models, cutting-edge developments and current challenges to overcome in the field, and the possibility of considering gut microbiome in the development of new drug.

Mechanistic insights into zearalenone-accelerated colorectal cancer in mice using integrative multi-omics approaches.

Zearalenone (ZEA), a secondary metabolite of Fusarium fungi found in cereal-based foods, promotes the growth of colon, breast, and prostate cancer cells in vitro. However, the lack of animal studies hinders a deeper mechanistic understanding of the cancer-promoting effects of ZEA. This study aimed to determine the effect of ZEA on colon cancer progression and its underlying mechanisms. Through integrative analyses of transcriptomics, metabolomics, metagenomics, and host phenotypes, we investigated the impact of a 4-week ZEA intervention on colorectal cancer in xenograft mice. Our results showed a twofold increase in tumor weight with the 4-week ZEA intervention. ZEA exposure significantly increased the mRNA and protein levels of BEST4, DGKB, and Ki67 and the phosphorylation levels of ERK1/2 and AKT. Serum metabolomic analysis revealed that the levels of amino acids, including histidine, arginine, citrulline, and glycine, decreased significantly in the ZEA group. Furthermore, ZEA lowered the alpha diversity of the gut microbiota and reduced the abundance of nine genera, including Tuzzerella and Rikenella. Further association analysis indicated that Tuzzerella was negatively associated with the expression of BEST4 and DGKB genes, serum uric acid levels, and tumor weight. Additionally, circulatory hippuric acid levels positively correlated with tumor weight and the expression of oncogenic genes, including ROBO3, JAK3, and BEST4. Altogether, our results indicated that ZEA promotes colon cancer progression by enhancing the BEST4/AKT/ERK1/2 pathway, lowering circulatory amino acid concentrations, altering gut microbiota composition, and suppressing short chain fatty acids production.

Skin, gut, and sand metagenomic data on placebo-controlled sandbox biodiversity intervention study.

The metagenomic data presented in this article are related to the published research of "A Placebo-controlled double-blinded test of the biodiversity hypothesis of immune-mediated diseases: Environmental microbial diversity elicits changes in cytokines and increase in T regulatory cells in young children" This database contains 16S ribosomal RNA (rRNA) metagenomics of sandbox sand and skin and gut microbiota of children in the intervention and placebo daycares. In intervention daycares, children aged 3-5 years were exposed to playground sand enriched with microbially diverse soil. In placebo daycares, children were exposed to visually similar as in intervention daycares, but microbially poor sand colored with peat. Sand, skin and gut metagenomics were analyzed at baseline and after 14 and 28 days of intervention by high throughput sequencing of bacterial 16S rRNA gene on the Illumina MiSeq platform. This dataset shows how skin bacterial community composition, including classes Gammaproteobacteria and Bacilli, changed, and how the relative abundance of over 30 bacterial genera shifted on the skin of children in the intervention treatment, while no shifts occurred in the placebo group.

High-fat diet induces intestinal mucosal barrier dysfunction in ulcerative colitis: emerging mechanisms and dietary intervention perspective.

The incidence of ulcerative colitis (UC) is increasing worldwide, but its pathogenesis remains largely unclear. The intestinal mucosa is a barrier that maintains the stability of the body's internal environment, and dysfunction of this barrier leads to the occurrence and aggravation of UC. A high-fat diet (HFD) contains more animal fat and low fiber, and accumulating evidence has shown that long-term intake of an HFD is associated with UC. The mechanism linking an HFD with intestinal mucosal barrier disruption is multifactorial, and it typically involves microbiota dysbiosis and altered metabolism of fatty acids, bile acids, and tryptophan. Dysbiosis-induced metabolic changes can enhance intestinal permeability through multiple pathways. These changes modulate the programmed death of intestinal epithelial cells, inhibit the secretion of goblet cells and Paneth cells, and impair intercellular interactions. Gut metabolites can also induce intestinal immune imbalance by stimulating multiple proinflammatory signaling pathways and decreasing the effect of anti-inflammatory immune cells. In this review, we critically analyze the molecular mechanisms by which an HFD disrupts the intestinal mucosal barrier (IMB) and contributes to the development of UC. We also discuss the application and future direction of dietary intervention in the treatment of the IMB and prevention of UC.

Changes in Lactate-related Fecal Microbiome in Hyperlactatemia Diabetic Dogs.

BACKGROUND/AIM: The correlation between the intestinal microbiome and endocrine disorders has recently been drawing attention as an important key for determining their pathology and clinical assessment. In this study, we evaluated the microbiome of dogs with insulin-dependent diabetes mellitus (IDDM) with respect to blood lactate. MATERIALS AND METHODS: Fecal samples were obtained from 17 subjects and real-time quantitative polymerase chain reaction determinations were performed to quantify the gene expression levels of lactate-producing and dysbiosis index-related bacteria. RESULTS: Expression levels of the lactate-producing bacteria Lactobacillus spp., Enterococcus spp., and Bifidobacterium spp., were confirmed in patients with high concentrations of lactate in the blood. The abundance of Enterococcus and Bifidobacterium was higher in diabetic dogs compared to that of non-diabetic dogs. When blood lactate concentrations were high, the abundance of Bifidobacterium also increased. CONCLUSION: Blood lactate levels influence the gut microbiome in dogs with IDDM. This study will help understand the gut microbiota in the context of diabetes in human and veterinary medicine.

Gut Microbiota Remodeling and Intestinal Adaptation to Lipid Malabsorption After Enteroendocrine Cell Loss in Adult Mice.

BACKGROUND & AIMS: Enteroendocrine cells (EECs) and their hormones are essential regulators of whole-body energy homeostasis. EECs sense luminal nutrients and microbial metabolites and subsequently secrete various hormones acting locally or at a distance. Impaired development of EECs during embryogenesis is life-threatening in newborn mice and humans due to compromised nutrient absorption. However, the physiological importance of the EEC system in adult mice has yet to be directedly studied. Herein, we aimed to determine the long-term consequences of a total loss of EECs in healthy adults on energy metabolism, intestinal transcriptome, and microbiota. METHODS: We depleted intestinal EECs by tamoxifen treatment of adult Neurog3fl/fl; Villin-CreERT2 male mice. We studied intestinal cell differentiation, food efficiency, lipid absorption, microbiota composition, fecal metabolites, and transcriptomic responses in the proximal and distal small intestines of mice lacking EECs. We also determined the high-fat diet-induced transcriptomic changes in sorted Neurog3eYFP/+ EECs. RESULTS: Induction of EEC deficiency in adults is not life-threatening unless fed with a high-fat diet. Under a standard chow diet, mice lose 10% of weight due to impaired food efficiency. Blood concentrations of cholesterol, triglycerides, and free fatty acids are reduced, and lipid absorption is impaired and delayed in the distal small intestine. Genes controlling lipogenesis, carbohydrate metabolism, and neoglucogenesis are upregulated. Microbiota composition is rapidly altered after EECs depletion and is characterized by decreased a-diversity. Bacteroides and Lactobacillus were progressively enriched, whereas Lachnospiraceae declined without impacting fecal short-chain fatty acid concentrations. CONCLUSIONS: EECs are dispensable for survival in adult male mice under a standard chow diet. The absence of EECs impairs intestinal lipid absorption, leading to transcriptomic and metabolic adaptations and remodeling of the gut microbiota.

Short-chain fatty acids as a link between diet and cardiometabolic risk: a narrative review.

AIM: Diet has a profound impact on cardiometabolic health outcomes such as obesity, blood glucose, blood lipids and blood pressure. In recent years, the gut microbiota has emerged as one of several potential key players explaining dietary effects on these outcomes. In this review we aim to summarise current knowledge of interaction between diet and gut microbiota focusing on the gut-derived microbial metabolites short-chain fatty acids and their role in modulating cardiometabolic risk. FINDINGS: Many observational and interventional studies in humans have found that diets rich in fibre or supplemented with prebiotic fibres have a favourable effect on the gut microbiota composition, with increased diversity accompanied by enhancement in short-chain fatty acids and bacteria producing them. High-fat diets, particularly diets high in saturated fatty acids, have shown the opposite effect. Several recent studies indicate that the gut microbiota modulates metabolic responses to diet in, e.g., postprandial blood glucose and blood lipid levels. However, the metabolic responses to dietary interventions, seem to vary depending on individual traits such as age, sex, ethnicity, and existing gut microbiota, as well as genetics. Studies mainly in animal models and cell lines have shown possible pathways through which short-chain fatty acids may mediate these dietary effects on metabolic regulation. Human intervention studies appear to support the favourable effect of short-chain fatty acid in animal studies, but the effects may be modest and vary depending on which cofactors were taken into consideration. CONCLUSION: This is an expanding and active field of research that in the near future is likely to broaden our understanding of the role of the gut microbiota and short-chain fatty acids in modulating metabolic responses to diet. Nevertheless, the findings so far seem to support current dietary guidelines encouraging the intake of fibre rich plant-based foods and discouraging the intake of animal foods rich in saturated fatty acids.

Microbiota dysbiosis and myasthenia gravis: Do all roads lead to Rome?

Dysregulated immune system with a failure to recognize self from non-self-antigens is one of the common pathogeneses seen in autoimmune diseases. The complex interplay of genetic and environmental factors is important for the occurrence and development of the disease. Among the environmental factors, disturbed gut microbiota (gut dysbiosis) has recently attracted particular attention, especially with advancement in human microbiome research. Although the alterations in microbiota have been seen in various autoimmune diseases, including those of nervous system, there is paucity of information on neuromuscular system diseases. Myasthenia gravis (MG) is one such rare autoimmune disease of neuromuscular junction, and is caused by generation of pathogenic autoantibodies to components of the postsynaptic muscle endplate. In the recent years, accumulating evidences have endorsed the key role of host microbiota, particularly those of gut, in the pathogenesis of MG. Differential microbiota composition, characterized by increased abundance of Fusobacteria, Bacteroidetes, and Proteobacteria, and decreased abundance of Actinobacteria and Firmicutes, has been seen in MG patients in comparison to healthy subjects. Disturbance of microbiota composition, particularly reduced ratio of Firmicutes/Bacteroidetes, alter the gut permeability, subsequently triggering the immunological response. Resultant reduction in levels of short chain fatty acids (SCFAs) is another factor contributing to the immunological response in MG patients. Modulation of gut microbiota via intervention of probiotics, prebiotics, synbiotics, postbiotics (metabiotics), and fecal microbiota transplantation (FMT) is considered to be the futuristic approach for the management of MG. This review summarizes the role of gut microbiota and their metabolites (postbiotics) in the progression of MG. Also, various bacteriotherapeutic approaches involving gut microbiota are discussed for the prevention of MG progression.

The effect of heart failure on gut microbial richness and diversity.

INTRODUCTION: With recent advances in genome sequencing technology, a large body of evidence has accumulated over the last few years linking alterations in microbiota with cardiovascular disease. In this study, we aimed to compare gut microbial composition using 16S ribosomal DNA (rDNA) sequencing techniques in patients with coronary artery disease (CAD) and stable heart failure (HF) with reduced ejection fraction and patients with CAD but with normal ejection fraction. We also studied the relationship between systemic inflammatory markers and microbial richness and diversity. METHODS: A total of 40 patients (19 with HF and CAD, 21 with CAD but without HF) were included in the study. HF was defined as left ventricular ejection fraction <40%. Only stable ambulatory patients were included in the study. Gut microbiota were assessed from the participants' fecal samples. The diversity and richness of microbial populations in each sample were assessed by the Chao1-estimated OTU number and the Shannon index. RESULTS: The Chao1-estimated OTU number and Shannon index were similar between HF and control groups. There was no statistically significant relationship between inflammatory marker levels (tumor necrosis factor-alpha, interleukin 1-beta, endotoxin, C-reactive protein, galectin-3, interleukin 6, and lipopolysaccharide-binding protein) and microbial richness and diversity when analyzed at the phylum level. CONCLUSION: In the current study, compared to patients with CAD but without HF, stable HF patients with CAD did not show changes in gut microbial richness and diversity. At the genus level Enterococcus sp. was more commonly identified in HF patients, in addition to certain changes in species levels, including increased Lactobacillus letivazi.

Evidence Supporting the Involvement of the Minority Compounds of Extra Virgin Olive Oil, through Gut Microbiota Modulation, in Some of the Dietary Benefits Related to Metabolic Syndrome in Comparison to Butter.

Extra virgin olive oil (EVOO) has proven to yield a better health outcome than other saturated fats widely used in the Western diet, including a distinct dysbiosis-preventive modulation of gut microbiota. Besides its high content in unsaturated fatty acids, EVOO also has an unsaponifiable polyphenol-enriched fraction that is lost when undergoing a depurative process that gives place to refined olive oil (ROO). Comparing the effects of both oils on the intestinal microbiota of mice can help us determine which benefits of EVOO are due to the unsaturated fatty acids, which remain the same in both, and which benefits are a consequence of its minority compounds, mainly polyphenols. In this work, we study these variations after only six weeks of diet, when physiological changes are not appreciated yet but intestinal microbial alterations can already be detected. Some of these bacterial deviations correlate in multiple regression models with ulterior physiological values, at twelve weeks of diet, including systolic blood pressure. Comparison between the EVOO and ROO diets reveals that some of these correlations can be explained by the type of fat that is present in the diet, while in other cases, such as the genus Desulfovibrio, can be better understood if the antimicrobial role of the virgin olive oil polyphenols is considered.

Is miR-223 Upregulation in Inflammatory Bowel Diseases a Protective Response?

Inflammatory bowel diseases (IBD) are characterized by chronic inflammation and damage of colonocytes with etiology of genetic, epigenetic and environmental factors. MicroRNA-223 (miR-223) has been found to be increased in both IBD patients and animal colitis models. However, contentious opinions relevant to the roles of miR-223 in IBD have been reported. Notwithstading that most studies have described that miR-223 has anti-inflammatory effects, several reports have progressed a pro-inflammatory view. In this review, we summarise both the anti-inflammatory and pro-inflammatory effects of miR-223 on key molecules in inflammatory responses in both animal models and in patients diagnosed with IBD and objectively discuss the possible basis for the discrepancies.

Use of Probiotics for Oral Candidiasis: State of the Art and Perspective. A Further Step Toward Personalized Medicine?

Oral candidiasis is an opportunistic infection conventionally treated with antifungal drugs. However, the increasing number of fungal infections, parallel to the rising conditions sustained by non-albicans species, pose critical issues related to escalating drug resistances differently acquired by different species. Meanwhile, the knowledge of the interplay between oral microbiota and its host suggests alternative antifungal therapies based on the administration of probiotics. Probiotics are live microorganisms beneficial to the host, and literature reports consistent evidence for their use to treat gut diseases. The present work aimed to overview the primary mechanisms through which probiotics act against Candida species and the current status of knowledge on their use in clinical practice, particularly concerning oral candidiasis.

Aryl hydrocarbon receptor nuclear translocator limits the recruitment and function of regulatory neutrophils against colorectal cancer by regulating the gut microbiota.

BACKGROUND: Although the role and mechanism of neutrophils in tumors have been widely studied, the precise effects of aryl hydrocarbon receptor nuclear translocator (ARNT) on neutrophils remain unclear. In this study, we investigated the roles of ARNT in the function of CD11b+Gr1+ neutrophils in colitis-associated colorectal cancer. METHODS: Wild-type (WT), ARNT myeloid-specific deficient mice and a colitis-associated colorectal cancer mouse model were used in this study. The level and functions of CD11b+Gr1+ cells were evaluated by flow cytometry and confocal microscopy. RESULTS: We found that ARNT deficiency drives neutrophils recruitment, neutrophil extracellular trap (NET) development, inflammatory cytokine secretion and suppressive activities when cells enter the periphery from bone marrow upon colorectal tumorigenesis. ARNT deficiency displays similar effects to aryl hydrocarbon receptor (AHR) deficiency in neutrophils. CXCR2 is required for NET development, cytokine production and recruitment of neutrophils but not the suppressive activities induced by Arnt-/- in colorectal cancer. The gut microbiota is essential for functional alterations in Arnt-/- neutrophils to promote colorectal cancer growth. The colorectal cancer effects of Arnt-/- neutrophils were significantly restored by mouse cohousing or antibiotic treatment. Intragastric administration of the feces of Arnt-/- mice phenocopied their colorectal cancer effects. CONCLUSION: Our results defined a new role for the transcription factor ARNT in regulating neutrophils recruitment and function and the gut microbiota with implications for the future combination of gut microbiota and immunotherapy approaches in colorectal cancer.

Factors associated with the composition of the gut microbiome in patients with established rheumatoid arthritis and its value for predicting treatment responses.

BACKGROUND: We aimed to investigate the gut microbiota of patients with established rheumatoid arthritis (RA) who have been managed with disease-modifying anti-rheumatic drugs (DMARDs) for a long time. We focused on factors that might affect composition of the gut microbiota. Furthermore, we investigated whether gut microbiota composition predicts future clinical responses to conventional synthetic DMARDs (csDMARDs) in patients with an insufficient response to initial therapy. METHODS: We recruited 94 patients with RA and 30 healthy participants. Fecal gut microbiome was analyzed by 16S rRNA amplificon sequencing; the resulting raw reads were processed based on QIIME2. Calypso online software was used for data visualization and to compare microbial composition between groups. For RA patients with moderate-to-high disease activity, treatment was changed after stool collection, and responses were observed 6 months later. RESULTS: The composition of the gut microbiota in patients with established RA was different from that of healthy participants. Young RA patients (< 45 years) had reduced richness, evenness, and distinct gut microbial compositions when compared with older RA patients and healthy individuals. Disease activity and rheumatoid factor levels were not associated with microbiome composition. Overall, biological DMARDs and csDMARDs, except sulfasalazine and TNF inhibitors, respectively, were not associated with the gut microbial composition in patients with established RA. However, the combination of Subdoligranulum and Fusicatenibacter genera was associated with a future good response to second-line csDMARDs in patients who showed an insufficient response to first-line csDMARDs. CONCLUSION: Gut microbial composition in patients with established RA is different from that in healthy individuals. Thus, the gut microbiome has the potential to predict responses of some RA patients to csDMARDs.

Microbiome analysis and fecal microbiota transfer in pediatric gastroenterology - a structured online survey in German-speaking countries.

PURPOSE: To assess the current attitude and the status quo towards the use of microbiome analysis and fecal microbiota transfer (FMT) in pediatric patients in German-speaking pediatric gastroenterology centers. METHODS: A structured online survey among all certified facilities of the German-speaking society of pediatric gastroenterology and nutrition (GPGE) was conducted from November 01, 2020, until March 30, 2021. RESULTS: A total of 71 centers were included in the analysis. Twenty-two centers (31.0%) use diagnostic microbiome analysis, but only a few perform analysis frequently (2; 2.8%) or regularly (1; 1.4%). Eleven centers (15.5%) have performed FMT as a therapeutic approach. Most of these centers use individual in-house donor screening programs (61.5%). One-third (33.8%) of centers rate the therapeutic impact of FMT as high or moderate. More than two-thirds (69.0%) of all participants are willing to participate in studies assessing the therapeutic effect of FMT. CONCLUSIONS: Guidelines for microbiome analyses and FMT in pediatric patients and clinical studies investigating their benefits are absolutely necessary to improve the patient-centered care in pediatric gastroenterology. The long-term and successful establishment of pediatric FMT centers with standardized procedures for patient selection, donor screening, application route, volume, and frequency of use is highly required to obtain a safe therapy.

Immunomodulatory role of oral microbiota in inflammatory diseases and allergic conditions.

In recent years, the interplay between oral microbiota and systemic disease has gained attention as poor oral health is associated with several pathologies. The oral microbiota plays a role in the maintenance of overall health, and its dysbiosis influences chronic inflammation and the pathogenesis of gum diseases. Periodontitis has also been associated with other diseases and health complications such as cancer, neurogenerative and autoimmune disorders, chronic kidney disease, cardiovascular diseases, rheumatic arthritis, respiratory health, and adverse pregnancy outcomes. The host microbiota can influence immune cell development and immune responses, and recent evidence suggests that changes in oral microbiota composition may also contribute to sensitization and the development of allergic reactions, including asthma and peanut allergies. Conversely, there is also evidence that allergic reactions within the gut may contribute to alterations in oral microbiota composition. Here we review the current evidence of the role of the oral microbiota in inflammatory diseases and health complications, as well as its future relevance in improving health and ameliorating allergic disease.

Berberine and rifaximin effects on small intestinal bacterial overgrowth: Study protocol for an investigator-initiated, double-arm, open-label, randomized clinical trial (BRIEF-SIBO study).

Introduction: Small intestinal bacterial overgrowth (SIBO) leads to non-specific abdominal discomfort and nutrient malabsorption. Currently, rifaximin is widely applied in SIBO based on its antibacterial and non-absorbable nature. Berberine is a natural component of many popular medicine plants that ameliorates intestinal inflammation in humans through its modification of the gut microbiota. Potential effect of berberine to the gut may provide therapeutic target for SIBO. We aimed to evaluate the effect of berberine compared with rifaximin on SIBO patients. Methods: This is an investigator-initiated, single-center, open-label, double-arm randomized controlled trial, termed BRIEF-SIBO (Berberine and rifaximin effects for small intestinal bacterial overgrowth). In total, 180 patients will be recruited and allocated to an intervention group (berberine) and a control group (rifaximin). Each participant will receive one 400 mg drug twice a day (800 mg daily) for 2 weeks. The total follow-up period is 6 weeks from the start of medication. The primary outcome is a negative breath test. The secondary outcomes include abdominal symptom relief and alteration in gut microbiota. Efficacy assessment will be performed every 2 weeks, as well as safety assessment during the treatment. The primary hypothesis is that berberine is not inferior to rifaximin for SIBO. Discussion: The BRIEF-SIBO study is the first clinical trial assessing the eradication effects of 2 weeks of berberine treatment in SIBO patients. The effect of berberine will be fully verified by using rifaximin as the positive control. The findings of this study may have implications for the management of SIBO, especially increasing the awareness of both physicians and patients who are suffering from long-term abdominal discomfort and avoiding excessive examination.