The microbiota, a complex assembly of microorganisms residing in various body systems, including the gastrointestinal tract, plays a crucial role in influencing various physiological processes in the human body. The dynamic nature of gut microbiota is especially pronounced in children and is influenced by factors like breastfeeding and antibiotic use. Dysbiosis, characterized by alterations in microbiota composition or function, is associated with several pediatric endocrine disorders, such as precocious puberty, polycystic ovarian syndrome, and diabetes mellitus. This review focuses on the intricate relationship between gut microbiota and the pediatric endocrine system. The aim of this narrative review is to critically examine the existing literature to elucidate the impact of gut microbiota on the pediatric endocrine system and associated disorders. Additionally, potential interventions, such as probiotics and current gaps in knowledge, will be discussed. Despite emerging treatments like probiotics, further research is needed to understand and validate their effectiveness in treating pediatric endocrine disorders associated with dysbiosis.

Lymph node metastasis (LNM) is a key factor in the prognosis of papillary thyroid carcinoma (PTC). This study explores the effect of intratumoral bacteria on LNM in PTC. The intrathyroidal microbiome is analyzed in 55 PTC patients by 16S rRNA gene sequencing. The CCK8 and Transwell assays determine the impact of bacteria on the proliferation and migration abilities of PTC cells. Xenograft tumor and bacterial colonization experiments are carried out using nude mice. We show that Lactobacillus is significantly decreased in PTC lesions from patients with LNM. Lactobacillus johnsonii (L. johnsonii) suppresses the proliferation and migration capability of PTC cells in vitro and in vivo. Bacterial gut colonization of L. johnsonii increases its abundance in tumors and inhibits PTC growth and LNM. These findings suggest that L. johnsonii can be harnessed for the development of innovative therapeutic strategies for PTC.

Parkinson's disease (PD) is a neurodegenerative disorder predominantly known for its motor symptoms such as bradykinesia, rigidity and tremor, but the disorder is also increasingly recognized for its association with impaired gastrointestinal function. The composition of the gut microbiome is known to be different in PD compared with healthy individuals. One of the bacterial families with increased abundance in people with PD is Lactobacillaceae. Interestingly, opposite effects have been ascribed to Lactobacillaceae in PD. A number of studies have linked Lactobacillaceae spp. in the gut to worse motor function, and to premature degradation of levodopa. However, other studies have linked administration of Lactobacillaceae-containing probiotics to improved motor function and reduced gastrointestinal problems. In this narrative review, we investigate this apparent paradox. The key to its understanding appears to lie in the specific species of Lactobacillaceae. The species L. plantarum in particular seemed to show a correlation with improved motor symptoms, as well as a reduction in intestinal inflammation, whereas L. brevis, L. curvatus and L. fermentum have properties that might be detrimental to people with PD.

Studies have linked gut microbiome and differentiated thyroid cancer (DTC). However, their causal relationships and potential mediating factors have not been well defined. Our study investigated the causal relationships between the gut microbiome, papillary thyroid cancer (PTC) and follicular thyroid cancer (FTC), as well as the mediating effect of potential blood metabolites, using genetic approaches.

Leveraging the summary statistics of gut microbial taxa, blood metabolites, PTC and FTC from the largest genome-wide association studies (GWAS) to date, we applied the bidirectional and mediation Mendelian randomization (MR) design. The multivariable MR approach based on Bayesian model averaging (MR-BMA) was used to prioritize the most likely causal taxa. Furthermore, metabolic pathway analysis was performed via the web-based Metaconflict 4.0.

After sensitivity analyses, we identified 4 taxa, 19 blood metabolites, and 5 gut bacterial pathways were causally associated with PTC. Similarly, 3 taxa, 31 blood metabolites, and 3 gut bacterial pathways were found to be causally associated with FTC, with 2 blood metabolites exhibiting bidirectional causal relationships. Metabolic pathway analysis revealed 8 significant pathways in PTC and FTC. MR-BMA analysis pinpointed species Bifidobacterium longum as the primary causal taxon for PTC and genus Bacteroides for FTC. The mediation MR analysis showed that sphingomyelin (d18:2/23:0, d18:1/23:1, d17:1/24:1) and 2-hydroxysebacate mediated the causal effects of specific gut microbiota on PTC and FTC, respectively.

The study suggested a causal relationship between several gut microbial taxa and DTC, and that specific blood metabolites might mediate this relationship.

Lung cancer (LC) remains the leading cause of cancer death globally. Recent reports have suggested that circulating microbial nucleic acids have potential as promising biomarkers for cancer liquid biopsies. However, circulating microbial profiles and their potential clinical value in LC patients remained unexplored. In this study, plasma samples from 76 LC patients, 9 liver cancer patients, 11 pancreatic cancer patients, and 53 healthy controls (HCs) were collected and underwent metagenomic analyses by whole genome sequencing. The composition and relative abundance of the microbial profiles were significantly different between the LC patients and HCs. A distinct plasma-based microbial profile was observed in LC patients. By differential analysis using MaAslin, 40 significant species between LC patients and HCs were identified. Five species were selected as optimal circulating microbial biomarkers for LC. The constructed classifier based on these five species showed an AUC of 0.9592, 0.9131, and 0.8077 in the discovery, validation, and additional validation cohorts, respectively. Furthermore, metagenomic profiles of 25 lung tumor tissue and plasma paired samples were analyzed and compared. The microbial diversity was significantly increased in plasma compared with the tumor tissue. Among the 13 shared core microbial species, 10 had no difference between the tumor tissue and paired plasma. In conclusion, circulating microbial nucleic acids in the plasma have potential as biomarkers for LC liquid biopsies. The microbiome in the tumor tissue was one of the possible sources of circulating microbial nucleic acids.

Purpose: Radiotherapy treatments are known to alter the gut microbiota. However, little is known regarding the effect of nuclear medicine treatments on gut microbiota, and it is established that nuclear medicine is inherently different from radiotherapy. To address this knowledge gap, we conducted a prospective study to identify changes in the gut microbiota of patients treated with [131I]NaI by comparing fecal samples before and after RAIT. Methods: Fecal samples of 64 patients (37 with thyroid cancer and 27 with hyperthyroidism) with indication for RAIT were collected 2 to 3 days before treatment and 8 to 10 days post-treatment. After DNA extraction, the gut microbiota's richness, diversity, and composition were analyzed by shotgun metagenomics. In addition, LEfSe was performed to compare compositional changes in specific bacteria. Results: Gut microbiome richness and diversity remained unchanged after RAIT, with few changes in its composition identified, especially in patients with hyperthyroidism. Conclusions: This study provides a conceptual and analytical basis for increasing our understanding of the effects of radiopharmaceuticals on gut microbiota. Our preliminary results indicate that RAIT, contrary to radiotherapy, does not cause major disruptions to the human gut microbiota.

Thyroid diseases are increasingly prevalent, posing significant challenges to patients' quality of life and placing substantial financial burdens on families and society. Despite these impacts, the underlying pathophysiology of many thyroid conditions remains poorly understood, complicating efforts in treatment, management, and prevention. Observational studies can identify associations between exposure variables and disease; however, they often struggle to account for confounding factors and reverse causation. Understanding disease occurrence, epidemiological trends, and clinical diagnosis, prevention, and treatment relies heavily on robust etiological research. Mendelian randomization, a method grounded in genetics and epidemiology, has been widely employed in studying the etiology of thyroid diseases, offering a solution to some of these challenges. This paper categorizes thyroid diseases into thyroid dysfunction and thyroid cancer, reviewing related Mendelian randomization studies. It further provides novel perspectives and approaches for investigating the mechanisms underlying thyroid diseases and designing intervention strategies.

Hashimoto's thyroiditis (HT) is an autoimmune disorder with unclear molecular mechanisms. While current diagnosis is well-established, understanding of the gut-thyroid axis in HT remains limited. This study aimed to uncover novel molecular signatures in HT by integrating gut metagenome and host transcriptome data (miRNA/mRNA), potentially elucidating disease pathogenesis and identifying new therapeutic targets.

We recruited 31 early HT patients and 30 healthy controls in a two-stage study (discovery and validation). Blood and fecal samples underwent RNA and metagenomic sequencing, respectively. Integrative analysis included differential expression, weighted correlation network, correlation and random forest analyses. Regression models and ROC curve analysis were used to evaluate the significance of identified molecular signatures in HT.

Integrative analysis revealed subtle changes in gut microbiota diversity and composition in early HT, increased abundance of Bacillota_A and Spirochaetota at the phylum level, and significant differences in 24 genera and 67 species. Ecological network analysis indicated an imbalance in the gut microbiota with reduced inhibitory interactions against pathogenic genera in HT. Functional analysis showed changes in infection- and immune-related pathways. Three characteristic species (Salaquimonas_sp002400845, Clostridium_AI_sp002297865, and Enterocloster_citroniae) were identified as most relevant to HT. Analysis of miRNA and mRNA expression profiles uncovered pathways related to immune response, inflammation, infection, metabolism, proliferation, and thyroid cancer in HT. Based on correlations with HT and interactions between them, six characteristic RNAs (hsa-miR-548aq-3p, hsa-miR-374a-5p, GADD45A, IRS2, SMAD6, WWTR1) were identified. Furthermore, our study uncovered significant gut microbiota-host transcriptome interactions in HT, revealing enrichment in metabolic, immune, and cancer-related pathways, particularly with strong associations among those 9 key molecular signatures. The validation stage confirmed improved HT classification accuracy by combining these signatures (AUC = 0.95, ACC = 0.85), suggesting their potential significance in understanding HT pathogenesis.

Our study reveals novel molecular signatures linking gut microbiome and host transcriptome in HT, providing new insights into the disease pathogenesis. These findings not only enhance our understanding of the gut-thyroid axis but also suggest potential new directions for therapeutic interventions in HT.

Autoimmune thyroid diseases (AITDs) are among the most prevalent organ-specific autoimmune disorders, with thyroid hormones playing a pivotal role in the gastrointestinal system's structure and function. Emerging evidence suggests a link between AITDs and the gut microbiome, which is a diverse community of organisms that are essential for digestion, absorption, intestinal homeostasis, and immune defense. Recent studies using 16S rRNA and metagenomic sequencing of fecal samples from AITD patients have revealed a significant correlation between a gut microbiota imbalance and the severity of AITDs. Progress in animal models of autoimmune diseases has shown that intervention in the gut microbiota can significantly alter the disease severity. The gut microbiota influences T cell subgroup differentiation and modulates the pathological immune response to AITDs through mechanisms involving short-chain fatty acids (SCFAs), lipopolysaccharides (LPSs), and mucosal immunity. Conversely, thyroid hormones also influence gut function and microbiota composition. Thus, there is a bidirectional relationship between the thyroid and the gut ecosystem. This review explores the pathogenic mechanisms of the gut microbiota and its metabolites in AITDs, characterizes the gut microbiota in Graves' disease (GD) and Hashimoto's thyroiditis (HT), and examines the interactions between the gut microbiota, thyroid hormones, T cell differentiation, and trace elements. The review aims to enhance understanding of the gut microbiota-thyroid axis and proposes novel approaches to mitigate AITD severity through gut microbiota modulation.

The gut morphology of Symphalangus syndactylus exhibits an intermediate structure that aligns with its consumption of fruit and ability to supplement its diet with leaves. The Siamang relies on its gut microbiome for energy extraction, immune system development, and the synthesis of micronutrients. Gut microbiome composition may be structured based on several factors such as age, sex, and habitat. No study has yet been carried out on the gut microbiota of the Hylobatidae members in Malaysia especially S. syndactylus.

This study aims to resolve the gut microbiome composition of S. syndactylus by using a fecal sample as DNA source, adapting high-throughput sequencing, and 16S rRNA as the targeted region.

A total of 1 272 903 operational taxonomic units (OTUs) reads were assigned to 22 phyla, 139 families, and 210 genera of microbes. The {Unknown Phylum} Bacteria-2 is the dominant phyla found across all samples. Meanwhile, {Unknown Phylum} Bacteria-2 and Firmicutes are genera that have the highest relative abundance found in the Siamang gut.

This study yields nonsignificance relationship between Siamang gut microbiome composition with these three factors: group, sex, and age.

This study conducts a systematic review through meta-analysis, comparing the composition and diversity of the gut microbiome in patients with esophageal cancer and healthy individuals, and explores the relationship between risk factors and related factors of esophageal cancer.

According to the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA), we comprehensively searched the databases of PubMed, Web of Science, Embase, Cochrane Library. In addition, we applied the R programming language version 4.0.3 and Stata 15.1 software for data analysis. We also implemented the Newcastle-Ottawa Scale (NOS), funnel plot analysis, Egger's test, and Begg's test to assess the risk of bias.

In this study, a total of 328 studies were identified through the literature search. Among them, 117 duplicate studies were removed, and 202 studies were excluded based on inclusion and exclusion criteria. Finally, 9 studies were included in the analysis, involving a total of 216 patients with esophageal carcinoma and 352 healthy controls. Four studies provided Chao1 index for quantitative consolidation (ES = 637.41, 95% CI: 549.16 to 725.66, p = 0.000, I2 = 98.2%). Two studies [27, 29] reported ACE index (ES = 438.89, 95% CI: 362.42 to 515.35, p = 0.000, I2 = 97%). Seven studies [26,27,29,30,32] reported the Shannon index for quantitative consolidation (ES = 4.38, 95% CI: 3.95 to 4.81, p = 0.000, I2 = 99%). At the phylum level, the abundance of Bacteroidetes(ES = 37.8, 95% CI: 25.75 to 49.85, p = 0.000, I2 = 87.2%) and Proteobacteria(ES = 7.48, 95% CI: 5.02 to 8.85, p = 0.04, I2 = 2.4%) have statistical difference between ESCC and HC. There was no significant difference between ESCC and HC in the abundance of genera(p>0.05).

This observational meta-analysis revealed that changes in the GM were correlated with esophageal carcinoma, and variations in some advantageous GM might involve regional differences. Additionally, the study aims to facilitate early diagnosis of esophageal cancer and improve screening and diagnostic efficiency.

Emerging research indicates the potential involvement of gut bacteria in the etiology of Graves' Disease (GD). However, the evidence regarding this matter is still conflicting. The primary objective of this investigation was to examine the correlation between gut microbiota and GD. A comprehensive search was conducted of the Cochrane Library, Scopus, Europe PMC, and Medline databases up until August 1, 2023, utilizing a combination of relevant keywords. This review incorporates literature that examined the composition of gut microbiota in patients with GD. We employed random-effect models to analyze the standardized mean difference (SMD) and present the outcomes together with their corresponding 95% confidence intervals (CIs). A total of ten studies were incorporated. The results of our meta-analysis indicated that patients with GD have a reduced alpha diversity of gut microbiota as evidence by a significant reduction of Chao1 (std. mean difference -0.58; 95% CI -0.90, -0.26, p=0.0004; I2 =61%), ACE (std. mean difference -0.64; 95% CI -1.09, -0.18, p=0.006; I2 =77%), and Shannon index (std. mean difference -0.71; 95% CI -1.25, -0.17, p=0.01; I2 =90%) when compared with healthy controls. At the phylum level, the abundance of Firmicutes was reduced in GD patients, while that of Bacteroidetes was increased. This study suggests a notable decrease in the richness and variety of gut microbiota among people diagnosed with GD in comparison with healthy controls.

The glioblastoma brain tumour (GBM) stands out as the most aggressive and resistant-to-treatment malignancy. Nevertheless, the gut-brain connection plays a pivotal role in influencing the growth and activation of the central nervous system. In this particular investigation, we aimed to assess and characterize the gut microbial ecosystem in GBM patients, both quantitatively and qualitatively. We collected faecal samples from 15 healthy volunteers and 25 GBM patients. To delve into the microbial content, we employed PCR-DGGE, targeting the V3 region of the 16S rRNA gene, and conducted qPCR to measure the levels of crucial intestinal bacteria. For a more in-depth analysis, high-throughput sequencing was performed on a selection of 20 random faecal samples (10 from healthy individuals and 10 from GBM patients), targeting the V3+V4 region of the 16S rRNA gene. Our findings from examining the richness and diversity of the gut microbiota unveiled that GBM patients exhibited significantly higher microbial diversity compared to healthy individuals. At the phylum level, Proteobacteria saw a significant increase, while Firmicutes experienced a noteworthy decrease in the GBM group. Moving down to the family level, we observed significantly elevated levels of Enterobacteriaceae, Bacteroidaceae, and Lachnospiraceae in GBM patients, while levels of Veillonellaceae, Rikenellaceae, and Prevotellaceae were notably lower. Delving into genera statistics, we noted a substantial increase in the abundance of Parasutterella, Escherichia-Shigella, and Bacteroides, alongside significantly lower levels of Ruminococcus 2, Faecalibacterium, and Prevotella_9 in the GBM group compared to the control group. Furthermore, when examining specific species, we found a significant increase in Bacteroides vulgatus and Escherichia coli in the GBM group. These observations collectively indicate a marked dysbiosis in the gut microbial composition of GBM patients. Additionally, the GBM group exhibited notably higher levels of alpha diversity when compared to the control group. This increase in diversity suggests a significant bacterial overgrowth in the gut of GBM patients in contrast to the controls. As a result, this research opens up potential avenues to gain a better understanding of the underlying mechanisms, pathways, and potential treatments for GBM, stemming from the significant implications of gut microbial dysbiosis in these patients.

The human gut microbiota creates a complex microbial ecosystem, characterized by its high population density, wide diversity, and complex interactions. Any imbalance of the intestinal microbiome, whether qualitative or quantitative, may have serious consequences for human health, including small intestinal bacterial overgrowth (SIBO). SIBO is defined as an increase in the number of bacteria (103-105 CFU/mL), an alteration in the bacterial composition, or both in the small intestine. The PubMed, Science Direct, Web of Science, EMBASE, and Medline databases were searched for studies on SIBO and related diseases. These diseases were divided into 12 groups: (1) gastrointestinal disorders; (2) autoimmune disease; (3) cardiovascular system disease; (4) metabolic disease; (5) endocrine disorders; (6) nephrological disorders; (7) dermatological diseases; (8) neurological diseases (9); developmental disorders; (10) mental disorders; (11) genetic diseases; and (12) gastrointestinal cancer. The purpose of this comprehensive review is to present the current state of knowledge on the relationships between SIBO and these 12 disease groups, taking into account risk factors and the causal context. This review fills the evidence gap on SIBO and presents a biological-medical approach to the problem, clearly showing the groups and diseases having a proven relationship with SIBO, as well as indicating groups within which research should continue to be expanded.

Temperature has been recognized as an important environmental factor affecting the composition and function of gut microbiota (GM). Although research on high-temperature impacts has been well studied, knowledge about the effect of cold exposure on GM remains limited. This narrative review aims to synthesize the latest scientific findings on the impact of cold exposure on mammalian GM, and its potential health implications. Chronic cold exposure could disrupt the α-diversity and the composition of GM in both experimental animals and wild-living hosts. Meanwhile, cold exposure could impact gut microbial metabolites, such as short-chain fatty acids. We also discussed plausible biological pathways and mechanisms by which cold-induced changes may impact host health, including metabolic homeostasis, fitness and thermogenesis, through the microbiota-gut-brain axis. Intriguingly, alterations in GM may provide a tool for favorably modulating the host response to the cold temperature. Finally, current challenges and future perspectives are discussed, emphasizing the need for translational research in humans. GM could be manipulated by utilizing nutritional strategies, such as probiotics and prebiotics, to deal with cold-related health issues and enhance well-being in populations living or working in cold environments.

In recent years, a growing number of studies have examined the relationship between thyroid pathophysiology and intestinal microbiota composition. The reciprocal influence between these two entities has been proven so extensive that some authors coined the term "gut-thyroid axis". However, since some papers reported conflicting results, several aspects of this correlation need to be clarified. This systematic review was conceived to achieve more robust information about: 1)the characteristics of gut microbiota composition in patients with the more common morphological, functional and autoimmune disorders of the thyroid; 2)the influence of gut microbial composition on micronutrients that are essential for the maintenance of thyroid homeostasis; 3)the effect of probiotics, prebiotics and synbiotics, some of the most popular over-the-counter products, on thyroid balance; 4)the opportunity to use specific dietary advice. The literature evaluation was made by three authors independently. A five steps strategy was a priori adopted. After duplicates removal, 1106 records were initially found and 38 reviews were finally included in the analysis. The systematic reviews of reviews found that: 1) some significant variations characterize the gut microbiota composition in patients with thyroid disorders. However, geographical clustering of most of the studies prevents drawing definitive conclusions on this topic; 2) the available knowledge about the effect of probiotics and synbiotics are not strong enough to suggest the routine use of these compounds in patients with thyroid disorders; 3) specific elimination nutrition should not be routine suggested to patients, which, instead have to be checked for possible micronutrients and vitamins deficiency, often owed to gastrointestinal autoimmune comorbidities.

This comprehensive review article delves into the critical role of the human microbiota in the development and management of endocrine-related diseases. We explore the complex interactions between the microbiota and the endocrine system, emphasizing the implications of microbiota dysbiosis for the onset and progression of various endocrine disorders. The review aims to synthesize current knowledge, highlighting recent advancements and the potential of novel therapeutic approaches targeting microbiota-endocrine interactions. Key topics include the impact of microbiota on hormone regulation, its role in endocrine pathologies, and the promising avenues of microbiota modulation through diet, probiotics, prebiotics, and fecal microbiota transplantation. We underscore the importance of this research in advancing personalized medicine, offering insights for more tailored and effective treatments for endocrine-related diseases.

Graves' disease (GD) and Graves' orbitopathy (GO) result from ongoing stimulation of the TSH receptor due to autoantibodies acting as persistent agonists. Orbital pre-adipocytes and fibroblasts also express the TSH receptor, resulting in expanded retro-orbital tissue and causing exophthalmos and limited eye movement. Recent studies have shown that GD/GO patients have a disturbed gut microbiome composition, which has been associated with increased intestinal permeability. This study hypothesizes that enhanced intestinal permeability may aggravate orbital inflammation and, thus, increase myofibroblast differentiation and the degree of fibrosis.

Two distinct cohorts of GO patients were studied, one of which was a unique cohort consisting of blood, fecal, and retro-orbital tissue samples. Intestinal permeability was assessed by measuring serum lipopolysaccharide-binding protein (LBP), zonulin, TLR5, and TLR9 ligands. The influx of macrophages and accumulation of T-cells and myofibroblast were quantified in orbital connective tissue. The NanoString immune-oncology RNA targets panel was used to determine the transcriptional profile of active fibrotic areas within orbital sections.

GO patients displayed significantly higher LBP serum concentrations than healthy controls. Within the MicroGO cohort, patients with high serum LBP levels also showed higher levels of zonulin and TLR5 and TLR9 ligands in their circulation. The increased intestinal permeability was accompanied by augmented expression of genes marking immune cell infiltration and encoding key proteins for immune cell adhesion, antigen presentation, and cytokine signaling in the orbital tissue. Macrophage influx was positively linked to the extent of T cell influx and fibroblast activation within GO-affected orbital tissues. Moreover, serum LBP levels significantly correlated with the abundance of specific Gram-negative gut bacteria, linking the gut to local orbital inflammation.

These results indicate that GO patients have enhanced intestinal permeability. The subsequent translocation of bacterial compounds to the systemic circulation may aggravate inflammatory processes within the orbital tissue and, as a consequence, augment the proportion of activated myofibroblasts, which actively secrete extracellular matrix leading to retro-orbital tissue expansion. These findings warrant further exploration to assess the correlation between specific inflammatory pathways in the orbital tissue and the gut microbiota composition and may pave the way for new microbiota-targeting therapies.

To investigate the association between thyroid functions and the oral microbiome diversity.

Data from the US National Health and Nutrition Examination Survey (NHANES; 2009-2012) were analyzed. Thyroid functions were defined using thyroid hormones and related biomarkers. Oral microbiome was measured using the observed number of amplicon sequence variants (ASVs) and the Bray-Curtis dissimilarity. Linear regression was used to estimate the average change (β) and 95% CI for the number of ASVs against thyroid functions, adjusted for sociodemographic variables, health conditions, urinary iodine status, and periodontitis. Non-metric multidimensional scaling (NMDS) was used to analyze the Bray-Curtis dissimilarity.

A total of 2943 participants were analyzed. The observed number of ASVs has a weighted mean of 128.9. Self-reported thyroid disease was associated with reduced number of ASVs (β = -9.2, 95% CI: -17.2, -1.2), if only adjusted for sociodemographic variables and health conditions. In the fully adjusted model, compared to normal thyroid function, both subclinical and clinical hyperthyroidism were associated with reduced number of ASVs (β = -59.6, 95% CI: -73.2, -46.0; β = -28.2, 95% CI: -50.0, -6.5, respectively). Thyroid peroxidase antibody level higher than the reference range was associated with higher observed ASV (β= 9.0, 95% CI: 1.2, 16.9). NMDS analysis suggested significant difference in oral microbiome composition between free triiodothyronine groups (P = .002), between free thyroxine groups (P = .015), and between thyroglobulin groups (P = .035).

Hyperthyroidism was associated with reduced oral microbiome diversity. Free triiodothyronine, free thyroxine, and thyroglobulin levels may alter the oral microbiome composition.

Numerous observational studies have indicated a link between the composition of gut microbiota and thyroid function. Nevertheless, the precise causal relationship between gut microbiota and thyroid function remains uncertain.

In this two-sample Mendelian randomization study, we utilized summary data from a genome-wide association study of gut microbiota composition in 18,340 participants from 24 cohorts, as well as summary statistics on thyroid hormones and thyroid-stimulating hormone from the ThyroidOmics Consortium and summary statistics on hypothyroidism and hyperthyroidism from the FinnGen R8 release. Five different methods, including inverse variance weighting, MR-Egger, weighted median, weighted mode, and simple mode, were employed to examine the causal relationship between gut microbiota and thyroid function. Reverse Mendelian randomization analysis was conducted for taxa identified as having a causal relationship with thyroid function in the Mendelian randomization analysis. To assess the robustness of the results, sensitivity analyses were conducted employing Cochran's Q test, MR-Egger intercept test, MR-PRESSO global test, and leave-one-out analysis.

Through MR analysis of 211 microbial taxa and 4 phenotypes, we identified a total of 34 gut microbiota taxa that were associated with the outcomes. After using the bonferroni method for multiple testing correction, phylum Actinobacteria (id.400) had a protective effect on hypothyroidism (OR=0.883, 95% CI: 0.817-0.955, P=0.002), and class Deltaproteobacteria (id.3087) had a protective effect on hyperthyroidism (OR=0.549, 95% CI: 0.374-0.805, P=0.002). According to the results of reverse MR analysis, no significant causal effect of the four phenotypes was found on gut microbiota. No significant horizontal pleiotropy was detected based on MR-Egger intercept test and MR-PRESSO global test.

Through two-sample MR analysis, we identified specific gut microbiota taxa at the genetic level that are predicted to have a causal relationship with thyroid function, which may serve as useful biomarkers for early disease diagnosis.

Hypoglycemic medications that could be co-administered with prebiotics and functional foods can potentially reduce the burden of metabolic diseases such as Type 2 Diabetes Mellitus (T2DM). The efficacy of drugs such as metformin and sulfonylureas can be enhanced by the activity of the intestinal microbiome elaborated metabolites. Functional foods such as prebiotics (e.g., oligofructose) and dietary fibers can treat a dysbiotic gut microbiome by enhancing the diversity of microbial niches in the gut. These beneficial shifts in intestinal microbiome profiles include an increased abundance of bacteria such as Faecalibacterium prauznitzii, Akkermancia muciniphila, Roseburia species, and Bifidobacterium species. An important net effect is an increase in the levels of luminal SCFAs (e.g., butyrate) that provide energy carbon sources for the intestinal microbiome in cross-feeding activities, with concomitant improvement in intestinal dysbiosis with attenuation of inflammatory sequalae and improved intestinal gut barrier integrity, which alleviates the morbidity of T2DM. Oligosaccharides administered adjunctively with pharmacotherapy to ameliorate T2DM represent current plausible treatment modalities.

Thyroid disorders are clinically characterized by alterations of L-3,5,3',5'-tetraiodothyronine (T4), L-3,5,3'-triiodothyronine (T3), and/or thyroid-stimulating hormone (TSH) levels in the blood. The most frequent thyroid disorders are hypothyroidism, hyperthyroidism, and hypothyroxinemia. These conditions affect cell differentiation, function, and metabolism. It has been reported that 40% of the world's population suffers from some type of thyroid disorder and that several factors increase susceptibility to these diseases. Among them are iodine intake, environmental contamination, smoking, certain drugs, and genetic factors. Recently, the intestinal microbiota, composed of more than trillions of microbes, has emerged as a critical player in human health, and dysbiosis has been linked to thyroid diseases. The intestinal microbiota can affect host physiology by producing metabolites derived from dietary fiber, such as short-chain fatty acids (SCFAs). SCFAs have local actions in the intestine and can affect the central nervous system and immune system. Modulation of SCFAs-producing bacteria has also been connected to metabolic diseases, such as obesity and diabetes. In this review, we discuss how alterations in the production of SCFAs due to dysbiosis in patients could be related to thyroid disorders. The studies reviewed here may be of significant interest to endocrinology researchers and medical practitioners.

Faecalibacterium prausnitzii, one of the most important bacteria of the human gut microbiota, produces butyrate (a short-chain fatty acid). Short-chain fatty acids are known to influence thyroid physiology and thyroid cancer's response to treatment. We aimed to analyze the relative abundance of Faecalibacterium prausnitzii on the gut microbiota of differentiated thyroid cancer patients compared to controls and its variation after radioiodine therapy (RAIT).

Fecal samples were collected from 37 patients diagnosed with differentiated thyroid cancer before and after radioiodine therapy and from 10 volunteers. The abundance of F. prausnitzii was determined using shotgun metagenomics.

Our study found that the relative abundance of F. prausnitzii is significantly reduced in thyroid cancer patients compared to volunteers. We also found that there was a mixed response to RAIT, with an increase in the relative and absolute abundances of this bacterium in most patients.

Our study confirms that thyroid cancer patients present a dysbiotic gut microbiota, with a reduction in F. prausnitzii's relative abundance. In our study, radioiodine did not negatively affect F. prausnitzii, quite the opposite, suggesting that this bacterium might play a role in resolving radiation aggression issues.

A new field of microbial research is the relationship between microorganisms and multicellular hosts. It is known that gut microbes can cause various endocrine system diseases, such as diabetes and thyroid disease. Changes in the composition or structure and the metabolites of gut microbes may cause gastrointestinal disorders, including ulcers or intestinal perforation and other inflammatory and autoimmune diseases. In recent years, reports on the interactions between intestinal microorganisms and endocrine system diseases have been increasingly documented. In the meantime, the treatment based on gut microbiome has also been paid much attention. For example, fecal microbiota transplantation is found to have a therapeutic effect on many diseases. As such, understanding the gut microbiota-endocrine system interactions is of great significance for the theranostic of endocrine system diseases. Herein, we summarize the relations of gut microbiome with endocrine system diseases, and discuss the potentials of regulating gut microbiome in treating those diseases. In addition, the concerns and possible solutions regarding the gut microbiome-based therapy are discussed.

Background: The gut is a target organ of thyroid hormone (TH) that exerts its action via the nuclear thyroid hormone receptor α1 (TRα1) expressed in intestinal epithelial cells. THs are partially metabolized via hepatic sulfation and glucuronidation, resulting in the production of conjugated iodothyronines. Gut microbiota play an important role in peripheral TH metabolism as they produce and secrete enzymes with deconjugation activity (β-glucuronidase and sulfatase), via which TH can re-enter the enterohepatic circulation. Summary: Intestinal epithelium homeostasis (the finely tuned balance between cell proliferation and differentiation) is controlled by the crosstalk between triiodothyronine and TRα1 and the presence of specific TH transporters and TH-activating and -inactivating enzymes. Patients and experimental murine models with a dominant-negative mutation in the TRα exhibit gross abnormalities in the morphology of the intestinal epithelium and suffer from severe symptoms of a dysfunctional gastrointestinal tract. Over the past decade, gut microbiota has been identified as an essential factor in health and disease, depending on its compositional and functional profile. This has led to a renewed interest in the so-called gut-thyroid axis. Disruption of gut microbial homeostasis (dysbiosis) is associated with autoimmune thyroid disease (AITD), including Hashimoto's thyroiditis, Graves' disease, and Graves' orbitopathy. These studies reviewed here provide new insights into the gut microbiota roles in thyroid disease pathogenesis and may be an initial step toward microbiota-based therapies in AITD. However, it should be noted that cause-effect mechanisms remain to be proven, for which prospective cohort studies, randomized clinical trials, and experimental studies are needed. Conclusion: This review aims at providing a comprehensive insight into the interplay between TH metabolism and gut homeostasis.

Diabetes and thyroid dysfunction are two closely related endocrine diseases. Increasing evidences show that gut microbiota plays an important role in both glucose metabolism and thyroid homeostasis. Meanwhile, copy number variation (CNV) of host salivary α-amylase gene (AMY1) has been shown to correlate with glucose homeostasis. Hence, we aim to characterize the gut microbiota and CNV of AMY1 in type 2 diabetes (T2D) patients with or without subclinical hypothyroidism (SCH).

High-throughput sequencing was used to analyze the gut microbiota of euthyroid T2D patients, T2D patients with SCH and healthy controls. Highly sensitive droplet digital PCR was used to measure AMY1 CN.

Our results revealed that T2D patients have lower gut microbial diversity, no matter with or without SCH. The characteristic taxa of T2D patients were Coriobacteriales, Coriobacteriaceae, Peptostreptococcaceae, Pseudomonadaceae, Collinsella, Pseudomonas and Romboutsia. Meanwhile, Escherichia/Shigella, Lactobacillus_Oris, Parabacteroides Distasonis_ATCC_8503, Acetanaerobacterium, Lactonifactor, uncultured bacterium of Acetanaerobacterium were enriched in T2D patients with SCH. Moreover, serum levels of free triiodothyronine (FT3) and free thyroxine (FT4) in T2D patients were both negatively correlated with richness of gut microbiota. A number of specific taxa were also associated with clinical parameters at the phylum and genus level. In contrast, no correlation was found between AMY1 CN and T2D or T2D_SCH.

This study identified characteristic bacterial taxa in gut microbiota of T2D patients with or without SCH, as well as the taxa associated with clinical indices in T2D patients. These results might be exploited in the prevention, diagnosis and treatment of endocrine disorders in the future.

The microbiota, as a complex of microorganisms in a particular ecosystem, is part of the wider term-microbiome, which is defined as the set of all genetic content in the microbial community. Imbalanced gut microbiota has a great impact on the homeostasis of the organism. Dysbiosis, as a disturbance in bacterial balance, might trigger or exacerbate the course of different pathologies. Small intestinal bacterial overgrowth (SIBO) is a disorder characterized by differences in quantity, quality, and location of the small intestine microbiota. SIBO underlies symptoms associated with functional gastrointestinal disorders (FGD) as well as may alter the presentation of chronic diseases such as heart failure, diabetes, etc. In recent years there has been growing interest in the influence of SIBO and its impact on the whole human body as well as individual systems. Therefore, we aimed to investigate the co-existence of SIBO with different medical conditions. The PubMed database was searched up to July 2022 and we found 580 original studies; inclusion and exclusion criteria let us identify 112 eligible articles, which are quoted in this paper. The present SIBO diagnostic methods could be divided into two groups-invasive, the gold standard-small intestine aspirate culture, and non-invasive, breath tests (BT). Over the years scientists have explored SIBO and its associations with other diseases. Its role has been confirmed not only in gastroenterology but also in cardiology, endocrinology, neurology, rheumatology, and nephrology. Antibiotic therapy could reduce SIBO occurrence resulting not only in the relief of FGD symptoms but also manifestations of comorbid diseases. Although more research is needed, the link between SIBO and other diseases is an important pathway for scientists to follow.

Papillary thyroid carcinoma (PTC) has a high incidence, and its proper treatment remains challenging. Therefore, identifying PTC progression markers is essential. Here, using 16S RNA sequences, we analyzed the PTC intratumor microbiome and its role in tumor progression. Substantial microbial abundance was detected in PTC from all patients. The tumor bacterial diversity in patients with advanced lesions (T3/T4) was significantly higher than that in patients with relatively mild lesions (T1/T2). Importantly, we identified signatures of eight tumor bacterial taxa highly predictive of PTC invasion status. Hence, microbial host factors-independent of the genomic composition of the tumor-may determine tumor behaviors and patient outcomes. Furthermore, the correlation between specific bacterial genus and thyroid hormones or autoimmune thyroid disease-related antibodies may indicate the potential contribution of the microbiome in the relationship between autoimmune thyroid disease or irregular thyroid function and PTC progression, intervention of which might therefore be worth exploring for advancing oncology care.

The gut microbiota plays a crucial role in healthy individuals as well as in patients with thyroid diseases, including thyroid cancer. Although the prognosis of differentiated thyroid cancer is predictable, that of some poorly differentiated, medullary, and anaplastic thyroid cancers remains unpromising. As the interaction between the gut microbiota and thyroid cancer has been gradually revealed in recent years, the thyroid gland, a crucial endocrine organ, is shown to have a complex connection with the body's metabolism and is involved in inflammation, autoimmunity, or cancer progression. Dysbiosis of the gut microbiota and its metabolites can influence changes in hormone levels and susceptibility to thyroid cancer through multiple pathways. In this review, we focus on the interactions of the gut microbiota with thyroid function diseases and thyroid cancer. In addition, we also discuss some potential new strategies for the prevention and treatment of thyroid disease and thyroid cancer. Our aim is to provide some possible clinical applications of gut microbiota markers for early diagnosis, treatment, and postoperative management of thyroid cancer. These findings were used to establish a better multi-disciplinary treatment and prevention management strategy and to individualize the treatment of patients in relation to their gut microbiota composition and pathological characteristics.

To investigate the association of differential metabolites with small intestinal microflora and maternal outcomes in subclinical hypothyroidism (SCH) during pregnancy.

The plasma of pregnant women in the SCH group and control group was analyzed by liquid chromatography-mass spectrometry (LC-MS), obtaining differential metabolites. Then, methane and hydrogen breath tests were performed in both groups, and basic clinical data and maternal outcome information were collected. Finally, differential metabolites were analyzed for small intestinal bacterial overgrowth (SIBO) and pregnancy outcomes using Spearman correlation analysis.

(1) Multivariate statistics: There were 564 different metabolites in positive ion mode and 226 different metabolites in negative ion mode. (2) The positive rate of the methane hydrogen breath test in the SCH group was higher than that in the control group (p<0.05). (3) KEGG pathway analysis revealed that differential metabolites were mainly involved in bile secretion, cholesterol metabolism, and other pathways. (4) Serum cholesterol (TC) and triglyceride (TG) levels and hypertensive disorder complicating pregnancy (HDCP) were higher in the SCH group (p<0.05), and newborn birth weight (BW) was lower than that in the control group (p<0.05). (5) SIBO was negatively correlated with glycocholic acid and BW, and positively correlated with TC. Glycocholic acid was negatively correlated with TG but positively correlated with BW. TG was positively correlated with HDCP.

Differential metabolites in the SCH group during pregnancy were disordered with small intestinal bacteria, which may affect pregnancy outcomes, and bile acids and cholesterol may be potential biomarkers for studying their mechanism of action.

Pregnant women are at high risk of developing subclinical hypothyroidism (SCH), and anti-thyroid peroxidase antibody (TPOAb) positivity can further inhibit thyroxine synthesis. Emerging evidence indicates that intestinal flora can modulate metabolic and immune homeostasis. The characteristics of intestinal flora of TPOAb-positive women with SCH in their second trimester of pregnancy have not been reported. This single-center prospective observational cohort study investigated gut microbial composition and metabolic function using sequencing of the 16S rRNA gene in fecal samples from 75 TPOAb-positive women with SCH and 90 TPOAb-negative women with SCH during their second trimester of pregnancy. Women were treated with no levothyroxine (LT₄), low-dose LT₄ (≤50ug/d), or high-dose LT₄ (>50ug/d). Taxonomic analysis showed Firmicutes and Bacteroidetes were the dominant phyla, followed by Actinobacteria and Proteobacteria. Faecalibacterium, Bacteroides, Prevotella 9, Bifidobacterium, Subdoligranulum, Lachnospira, and Megamonas were the predominant genera. The intestinal flora of TPOAb-positive women with SCH who received no LT₄ was characterized by bacterial amplicon sequence variants (ASVs)/operational taxonomic units (OTUs) enriched in the genus Subdoligranulum. The intestinal flora of TPOAb-positive women with SCH who received low-dose or high-dose LT₄ were characterized by bacterial ASVs/OTUs depleted of the species Ruminococcus sp._or Bacteroides massiliensis, respectively. A total of 19 metabolic functions of intestinal flora, mainly involving lipid and amino acid metabolism, discriminated TPOAb-positive and TPOAb-negative women with SCH. Our study suggests that there are differences in the composition and metabolic function of intestinal flora of TPOAb-positive and TPOAb-negative women with SCH treated with different doses of LT₄ in the second trimester of pregnancy. The findings provide insight into intestinal flora as novel targets for the treatment of TPOAb-positive women with SCH during pregnancy.

Thyroid hormone withdrawal (THW) in postoperative thyroid cancer patients who need always accompanied by complications (e.g., dyslipidemia and constipation). At present, there are no effective and safe means to alleviate these complications.

We aimed to assess the oral-gut microbiota profiles in THW patients then investigate whether probiotics could alleviating alleviate THW related complications and investigate whether these therapeutic effects were associated with the oral-gut microbiota state.

Fifty eligible thyroid carcinoma patients undergoing thyroidectomy were randomly assigned to receive probiotics or placebo during THW. Complications were assessed through validated questionnaires and plasma lipid indicators. The complex probiotics preparation was composed of Bifidobacterium infantis, Lactobacillus acidophilus, Enterococcus faecalis, and Bacillus cereus.

Probiotics alleviated lack of energy, constipation, weight gain, and dry mouth and decreased the levels of fecal/serum LPS and plasma lipid indicators (total cholesterol, triglycerides, low-density lipoprotein, and apolipoprotein A) (P < 0.05). Gut and oral microbial diversity were significantly decreased after THW, while an increased microbial dysbiosis index (MDI) was observed. Probiotics distinctly restored the gut and oral microbial diversity. Increased Holdemanella, Enterococcus, and Coprococcus_2, while decreased Fusobacterium, Eubacterium_ruminantium_group, Ruminococcus_1, and Parasutterella in the gut were found after probiotics intervention. Lack of energy, constipation, weight gain, and dyslipidemia were seen to be related to the above microbiota. In addition, probiotics reduced oral Prevotella_9, Haemophilus, Fusobacterium, and Lautropia, which were positively correlated with the occurrence of dry mouth.

Probiotics reduce the incidence of complications in patients after THW, which may be related to modifying the oral and gut microbiota.

[https://clinicaltrials.gov/], identifier America Clinical Trial Registry NCT03574051.

Emerging studies have provided a preliminary understanding of the thyroid-gut axis, indicating that intestinal microbiota and its metabolites may act directly or indirectly on the thyroid by influencing intestinal microelements uptake, iodothyronine conversion and storage, and immune regulation, providing new insights into the pathogenesis of thyroid disorders and clinical management strategies. However, the research on gut microbiota and thyroid has only presented the tip of the iceberg. More robust clinical data and basic experiments are still required to elucidate the specific relationships and mechanisms in the future. Here we will characterize the associations between the microbiota and thyroid diseases to evaluate their potential implications in the pathophysiology and open up scientific avenues for future precision studies of the thyroid-gut axis.

Due to its aggressive nature and low survival rate, esophageal cancer is one of the deadliest cancer. While the intestinal microbiome significantly influences human health and disease. This research aimed to investigate and characterize the relative abundance of intestinal bacterial composition in esophageal cancer patients. The fecal samples were collected from esophageal cancer patients (n = 15) and healthy volunteers (n = 10). The PCR-DGGE was carried out by focusing on the V3 region of the 16S rRNA gene, and qPCR was performed for Bacteroides vulgatus, Escherichia coli, Bifidobacterium, Clostridium leptum and Lactobacillus. High-throughput sequencing of the 16S rRNA gene targeting the V3+V4 region was performed on 20 randomly selected samples. PCR-DGGE and High-throughput diversity results showed a significant alteration of gut bacterial composition between the experimental and control groups, which indicates the gut microbial dysbiosis in esophageal cancer patients. At the phylum level, there was significant enrichment of Bacteroidetes, while a non-significant decrease of Firmicutes in the experimental group. At family statistics, a significantly higher level of Bacteroidaceae and Enterobacteriaceae, while a significantly lower abundance of Prevotellaceae and Veillonellaceae were observed. There was a significantly high prevalence of genera Bacteroides, Escherichia-Shigella, while a significantly lower abundance of Prevotella_9 and Dialister in the experimental group as compared to the control group. Furthermore, the species analysis also showed significantly raised level of Bacteroides vulgatus and Escherichia coli in the experimental group. These findings revealed a significant gut microbial dysbiosis in esophageal cancer patients. So, the current study can be used for the understanding of esophageal cancer treatment, disease pathway, mechanism, and probiotic development.