EVOLUTION: Of Mice . . .

Oral bacteria directly affect the disease status of dental caries and periodontal diseases. The dynamic oral microbiota cooperates with the host to reflect the information and status of immunity and metabolism through two-way communication along the oral cavity and the systemic organs. The oral cavity is one of the most important interaction windows between the human body and the environment. The microenvironment at different sites in the oral cavity has different microbial compositions and is regulated by complex signaling, hosts, and external environmental factors. These processes may affect or reflect human health because certain health states seem to be related to the composition of oral bacteria, and the destruction of the microbial community is related to systemic diseases. In this review, we discussed emerging and exciting evidence of complex and important connections between the oral microbes and multiple human systemic diseases, and the possible contribution of the oral microorganisms to systemic diseases. This review aims to enhance the interest to oral microbes on the whole human body, and also improve clinician's understanding of the role of oral microbes in systemic diseases. Microbial research in dentistry potentially enhances our knowledge of the pathogenic mechanisms of oral diseases, and at the same time, continuous advances in this frontier field may lead to a tangible impact on human health. 

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Oral microbiota in human systematic diseases

This review covers current knowledge of selenium in the dietary intake, its bioavailability, metabolism, functions, biomarkers, supplementation and toxicity, as well as its relationship with diseases and gut microbiota specifically on the symbiotic relationship between gut microflora and selenium status. Selenium is essential for the maintenance of the immune system, conversion of thyroid hormones, protection against the harmful action of heavy metals and xenobiotics as well as for the reduction of the risk of chronic diseases. Selenium is able to balance the microbial flora avoiding health damage associated with dysbiosis. Experimental studies have shown that inorganic and organic selenocompounds are metabolized to selenomethionine and incorporated by bacteria from the gut microflora, therefore highlighting their role in improving the bioavailability of selenocompounds. Dietary selenium can affect the gut microbial colonization, which in turn influences the host's selenium status and expression of selenoproteoma. Selenium deficiency may result in a phenotype of gut microbiota that is more susceptible to cancer, thyroid dysfunctions, inflammatory bowel disease, and cardiovascular disorders. Although the host and gut microbiota benefit each other from their symbiotic relationship, they may become competitors if the supply of micronutrients is limited. Intestinal bacteria can remove selenium from the host resulting in two to three times lower levels of host's selenoproteins under selenium-limiting conditions. There are still gaps in whether these consequences are unfavorable to humans and animals or whether the daily intake of selenium is also adapted to meet the needs of the bacteria.

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Selenium in Human Health and Gut Microflora: Bioavailability of Selenocompounds and Relationship With Diseases.

Effects of Polygonatum sibiricum saponin on hyperglycemia, gut microbiota composition and metabolic profiles in type 2 diabetes mice.

The relationship among the gut microbiome, global fecal metabolites and rheumatoid arthritis (RA) has not been systematically evaluated. In this study, we performed 16S rDNA sequencing and liquid chromatography-tandem mass spectrometry (LC-MS/MS)-based nontargeted metabolomic profiling on feces of 26 untreated RA patients and 26 healthy controls. Twenty-six genera and forty-one MS2-identified metabolites were significantly altered in the RA patients. Klebsiella, Escherichia, Eisenbergiella and Flavobacterium were more abundant in the RA patients, while Fusicatenibacter, Megamonas and Enterococcus were more abundant in the healthy controls. Function prediction analysis demonstrated that the biosynthesis pathways of amino acids, such as L-arginine and aromatic amino acids, were depleted in the RA group. In the metabolome results, fecal metabolites including glycerophospholipids (PC(18:3(9Z,12Z,15Z)/16:1(9Z)), lysoPE 19:1, lysoPE 18:0, lysoPC(18:0/0:0)), sphingolipids (Cer(d18:0/16:0), Cer(d18:0/12:0), Cer(d18:0/14:0)), kynurenic acid, xanthurenic acid and 3-hydroxyanthranilic acid were remarkably altered between the RA patients and healthy controls. Dysregulation of pathways, such as tryptophan metabolism, alpha-linolenic acid metabolism and glycerophospholipid metabolism, may contribute to the development of RA. Additionally, we revealed that the gut microbiome and metabolites were interrelated in the RA patients, while Escherichia was the core genus. By depicting the overall landscape of the intestinal microbiome and metabolome in RA patients, our study could provide possible novel research directions regarding RA pathogenesis and targeted therapy.

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The Gut Microbiome and Metabolites Are Altered and Interrelated in Patients With Rheumatoid Arthritis

The aim of our study was to investigate the relationship among the gut microbiota community, metabolite profiles and thyroid carcinoma (TC). First, 30 TC patients and 35 healthy controls (HCs) fecal samples were applied to characterize the gut microbial community using 16S rRNA gene sequencing. Differential microbiota compositions were observed, with significant enrichment of 19 and depletion of 8 genera in TC samples compared to those in HCs (Q value 1.0 and p < 0.05) were observed and correlated to each other. Eight metabolites combined with 5 genera were more effective in distinguishing TC patients from HCs (AUC = 0.97). In conclusion, our study presents a comprehensive landscape of the gut microbiota and metabolites in TC patients, and provides a research direction of the mechanism of interaction between gut microbiota alteration and TC pathogenesis.

https://onlinelibrary.wiley.com/doi/pdf/10.1002/ijc.32007

Alterations in the gut microbiota and metabolite profiles of thyroid carcinoma patients

Colorectal cancer (CRC) is a common cancer worldwide with complex etiology. Fusobacterium nucleatum (F. nucleatum), an oral symbiotic bacterium, has been linked with CRC in the past decade. A series of gut microbiota studies show that CRC patients carry a high abundance of F. nucleatum in the tumor tissue and fecal, and etiological studies have clarified the role of F. nucleatum as a pro-carcinogenic bacterium in various stages of CRC. In this review, we summarize the biological characteristics of F. nucleatum and the epidemiological associations between F. nucleatum and CRC, and then highlight the mechanisms by which F. nucleatum participates in CRC progression, metastasis, and chemoresistance by affecting cancer cells or regulating the tumor microenvironment (TME). We also discuss the research gap in this field and give our perspective for future studies. These findings will pave the way for manipulating gut F. nucleatum to deal with CRC in the future.

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Fusobacterium nucleatum Acts as a Pro-carcinogenic Bacterium in Colorectal Cancer: From Association to Causality.

Background: Drugs can alter the gut microbiota structure, and gut microbiota dysbiosis in turn is correlated with drug side effects through the intestinal endotoxemia hypothesis. Whether antithyroid drugs (including methimazole and propylthiouracil) cause gut microbiota dysbiosis and whether the gut microbiota is correlated with antithyroid drugs induced liver injury is unknown. Methods: Initial Graves’ disease patients were randomly divided into the methimazole group (n=20) and the propylthiouracil group (n=20) and were followed up every two weeks; 50 healthy controls were also included. The structure and function of gut microbiota were compared from the cross sectional and longitudinal levels. The correlation between the gut microbiota and clinical parameters was also determined. In addition, Sprague-Dawley rats were randomly allotted into 6 groups, including four drug groups, which received daily doses of methimazole (1.5 mg/kg/day; 2.5 mg/kg/day) or propylthiouracil (7.5 mg/kg/day; 12.5 mg/kg/day) by oral gavage, and two control groups received the vehicle. In addition to the indexes mentioned above, intestinal barrier-related indexes were also performed. Results: Results from both clinical trials and animal studies indicate that use or nonuse of drugs, different drugs, different doses and different time points all altered gut microbiota structure; and the liver function related indexes all increased which correlated with gut microbiota. In addition, lipopolysaccharide-related pathways and the lipopolysaccharide concentration in feces and serum all increased after antithyroid drugs administration. These results consistent with the destroyed intestinal barrier in animal study after antithyroid drugs administration. Conclusions: We verified that antithyroid drugs could cause gut microbiota dysbiosis and that the gut microbiota may in turn be correlated with antithyroid drugs-induced liver injury through the intestinal endotoxemia hypothesis.

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Gut Microbiota Participates in Antithyroid Drug Induced Liver Injury Through the Lipopolysaccharide Related Signaling Pathway.

Background 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. Purpose 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. Methods 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. Results 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. Conclusion Probiotics reduce the incidence of complications in patients after THW, which may be related to modifying the oral and gut microbiota. Clinical Trial Registration [https://clinicaltrials.gov/], identifier America Clinical Trial Registry NCT03574051.

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Randomized Clinical Trial: Probiotics Alleviated Oral-Gut Microbiota Dysbiosis and Thyroid Hormone Withdrawal-Related Complications in Thyroid Cancer Patients Before Radioiodine Therapy Following Thyroidectomy

Colorectal cancer patients with synchronous liver metastases (CRSLM) can be treated by simultaneous surgery, that is the primary tumor and liver metastasis are removed at the same time. However, criteria for simultaneous surgery are underwent continuously modified and expanded. An appropriate selection of adequate candidates for simultaneous surgery is vital to get best benefits. A retrospective study including CRSLM patients underwent simultaneous surgical treatment was conducted. CRSLM patients from SEER database were screened as development set, while CRSLM patients in Harbin (China) were enrolled as validation set. Overall survival (OS) and cancer-specific survival (CSS) were applied as end-point. Variables were screen by LASSO-Cox regression, then Cox regression was applied to construct 1-, 3- and 5-year OS, and CSS nomograms. Nomograms were compared to TMN stage for survival prediction and evaluated by concordance indexes (C-indexes), Time-dependent receiver operating characteristic (ROC) curves, Decision Curve Analysis (DCA). 1347 and 112 CRSLM patients were included in the development set and validation set respectively. Nine factors were found associated with OS and CSS, i.e., Age, Primary Site, Differentiation grade, Histology type, T stage, N stage, Tumor size, Chemotherapy, CEA. Compared to the TNM stage, OS nomogram in development set and validation set got C-indexes values of 0.701 vs 0.641, 0.670 vs 0.557 respectively. Meanwhile, compared to the TNM stage, CSS nomogram in development set and validation set got C-indexes values of 0.704 vs 0.649, 0.677 vs 0.569 respectively. AUC values of the OS and CSS nomograms were higher than the TNM stage, DCA showed the OS and CSS nomograms got more clinical net benefit than the TNM stage, in both the development set and validation set. Our nomograms for predicting survival might be helpful to identify the right CRSLM patients who can get most benefit from simultaneous surgery.

Development and validation of survival nomograms in colorectal cancer patients with synchronous liver metastases underwent simultaneous surgical treatment of primary and metastatic lesions.

Baiqiang Lin

Papers

Alterations in the gut microbiota and metabolite profiles of thyroid carcinoma patients

Fusobacterium nucleatum Acts as a Pro-carcinogenic Bacterium in Colorectal Cancer: From Association to Causality.

Gut Microbiota Participates in Antithyroid Drug Induced Liver Injury Through the Lipopolysaccharide Related Signaling Pathway.

Randomized Clinical Trial: Probiotics Alleviated Oral-Gut Microbiota Dysbiosis and Thyroid Hormone Withdrawal-Related Complications in Thyroid Cancer Patients Before Radioiodine Therapy Following Thyroidectomy

Development and validation of survival nomograms in colorectal cancer patients with synchronous liver metastases underwent simultaneous surgical treatment of primary and metastatic lesions.