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Liu C, Chao S, Jia L, Yang Q, Chen Q, Niu Y. Integrative analyses of 16S rDNA sequencing and serum metabolomics demonstrate significant roles for the oral microbiota and serum metabolites in post-kidney transplant diabetes mellitus. Microbiol Spectr 2025:e0089225. [PMID: 40492760 DOI: 10.1128/spectrum.00892-25] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/04/2025] [Accepted: 05/09/2025] [Indexed: 06/12/2025] Open
Abstract
Oral microbiota and serum metabolites play crucial roles in diabetes, but their relationship with post-transplant diabetes mellitus (PTDM), a common complication post-kidney transplantation, is not well characterized. This study investigated the relationship of oral microbiota and serum metabolites with PTDM using integrative analysis of 16S rDNA sequencing and serum metabolomics. We recruited 61 kidney transplant recipients, including 30 in the PTDM group and 31 in normal glucose tolerance controls. Oral samples and serum samples were collected from all the kidney transplant patients to perform 16S rDNA sequencing and serum metabolomics analysis. We annotated 689 oral microbial species, including 134 species unique to the PTDM group and 157 species unique to the control group. PTDM group showed upregulation of 36 metabolites and downregulation of 19 metabolites. Based on the random forest machine learning algorithm, genera such as UCG-005 (AUC = 0.9355), Succinivibrio (AUC = 0.8108); Akkermansia (AUC = 0.7742), Anaerovibrio (AUC = 0.2667), and Schwartzia (AUC = 0.2667), and serum metabolites such as LPI 18:0 (AUC: 0.8086), methylglyoxal (AUC: 0.7946), Vulgarin (AUC: 0.7828), 2-mercaptobenzothiazole (AUC: 0.7591), and PI(18:0/20:3(5Z,8Z,11Z)) (AUC: 0.7419) showed high diagnostic potential and may serve as clinical biomarkers. Furthermore, clinical indicators in PTDM patients, such as creatinine, cystatin C, and urea, showed a significant association with the differential oral microbiota and serum metabolites. Dysbiosis in the oral microbiota of the PTDM patients was associated with changes in the serum metabolites and alterations in their functions. These findings provide new insights toward identifying mechanisms by which oral microbiota and serum metabolites contribute to the development of PTDM.IMPORTANCEThis study reveals an imbalance in oral microbiota in patients with post-transplant diabetes and uncovers the potential relationship between oral microbiota and serum metabolites. These findings provide new insights into the role of oral microbiota and serum metabolites in the treatment of post-transplant diabetes, offering relevant biomarkers for clinicians and future research.
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Affiliation(s)
- Chao Liu
- Department of Organ Transplantation, Affiliated Hospital of Guizhou Medical University, Guiyang, Guizhou, China
- Urinary Surgery, The Affiliated Hospital of Guizhou Medical University, Guiyang, Guizhou, China
| | - Sheng Chao
- Department of Organ Transplantation, Affiliated Hospital of Guizhou Medical University, Guiyang, Guizhou, China
| | - Lei Jia
- Department of Organ Transplantation, Affiliated Hospital of Guizhou Medical University, Guiyang, Guizhou, China
| | - Qizhen Yang
- Department of Organ Transplantation, Affiliated Hospital of Guizhou Medical University, Guiyang, Guizhou, China
| | - Qian Chen
- Department of Organ Transplantation, Affiliated Hospital of Guizhou Medical University, Guiyang, Guizhou, China
| | - Yulin Niu
- Department of Organ Transplantation, Affiliated Hospital of Guizhou Medical University, Guiyang, Guizhou, China
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Wadan AHS, Moshref AS, Emam AM, Bakry YG, Khalil BO, Chaurasia A, Ibrahim RAH, Badawy T, Mehanny SS. Mitochondrial dysfunction as a key player in aggravating periodontitis among diabetic patients: review of the current scope of knowledge. NAUNYN-SCHMIEDEBERG'S ARCHIVES OF PHARMACOLOGY 2025:10.1007/s00210-025-04025-x. [PMID: 40272516 DOI: 10.1007/s00210-025-04025-x] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Subscribe] [Scholar Register] [Received: 12/08/2024] [Accepted: 03/05/2025] [Indexed: 04/25/2025]
Abstract
Periodontitis is a prevalent inflammatory disease that leads to significant periodontal tissue destruction and compromised dental health, with its severity exacerbated in individuals with Diabetes Mellitus (DM). This review explores the complex relationship between mitochondrial dysfunction and periodontitis in diabetic patients. Recent studies indicate that the excessive production of reactive oxygen species (ROS), primarily generated by dysfunctional mitochondrial electron transport chain (ETC) complexes, contributes to oxidative stress (OS) and subsequent periodontal tissue damage. The interplay between impaired mitochondrial biogenesis, apoptosis of periodontal cells, and ROS accumulation highlights a critical area of concern in understanding the pathophysiology of diabetic periodontitis. Furthermore, altered glycemic control due to inflammatory processes associated with periodontitis may perpetuate a cyclical detriment to oral and systemic health. This review aims to highlight the mechanistic roles of mitochondrial dysfunction in the aggravation of periodontitis among diabetic patients, emphasizing further research to identify potential therapeutic targets and improve treatment efficacy for this dual pathology.
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Affiliation(s)
- Al-Hassan Soliman Wadan
- Department of Oral Biology, Faculty of Dentistry, Galala University, Galala City, Suez, Egypt.
| | | | | | | | | | - Akhilanand Chaurasia
- Department of Oral Medicine and Radiology, King George'S Medical University, Lucknow, India
| | - Reham A H Ibrahim
- Department of Oral Biology, Faculty of Dentistry, Galala University, Galala City, Suez, Egypt
| | - Tamer Badawy
- Department of Oral Biology, Faculty of Dentistry, Galala University, Galala City, Suez, Egypt
- Department of Oral Biology, Faculty of Dentistry, Cairo University, Cairo, Egypt
| | - Samah S Mehanny
- Department of Oral Biology, Faculty of Dentistry, Galala University, Galala City, Suez, Egypt
- Department of Oral Biology, Faculty of Dentistry, Cairo University, Cairo, Egypt
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Leech SM, Barrett HL, Dorey ES, Mullins T, Laurie J, Nitert MD. Consensus approach to differential abundance analysis detects few differences in the oral microbiome of pregnant women due to pre-existing type 2 diabetes mellitus. Microb Genom 2025; 11. [PMID: 40232948 DOI: 10.1099/mgen.0.001385] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 04/17/2025] Open
Abstract
Oral microbiome dysbiosis has been proposed as a potential contributing factor to rising rates of diabetes in pregnancy, with oral health previously associated with an increased risk of numerous chronic diseases and complications in pregnancy, including gestational diabetes mellitus (GDM). However, whilst most studies examining the relationship between GDM and the oral microbiome identify significant differences, these differences are highly variable between studies. Additionally, no previous research has examined the oral microbiome of women with pre-existing type 2 diabetes mellitus (T2DM), which has greater risks of complications to both mother and baby. In this study, we compared the oral microbiome of 11 pregnant women with pre-existing T2DM with 28 pregnant normoglycaemic controls. We used shotgun metagenomic sequencing to examine buccal swab and saliva rinse samples at two time points between 26 and 38 weeks of gestation. To reduce variation caused by the choice of differential abundance analysis tool, we employed a consensus approach to identify differential taxa and pathways due to diabetes status. Differences were identified at the late time point only. In swab samples, there was increased Flavobacteriaceae, Capnocytophaga, Capnocytophaga gingivalis SGB2479, Capnocytophaga leadbetteri SGB2492 and Neisseria elongata SGB9447 abundance in T2DM as well as increased Shannon diversity and richness. In rinse samples, there was an increased abundance of Haemophilus, Pasteurellaceae, Pasteurellales and Proteobacteria. In contrast to studies of the oral microbiome in T2DM or GDM that use a single differential abundance analysis tool, our consensus approach identified few differences between pregnant women with and without T2DM.
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Affiliation(s)
- Sophie M Leech
- School of Chemistry and Molecular Biosciences, The University of Queensland, St Lucia, QLD 4072, Australia
| | - Helen L Barrett
- Obstetric Medicine, Royal Hospital for Women, Randwick, NSW, Australia
- Faculty of Medicine, University of New South Wales, Sydney, NSW, Australia
- Mater Research Institute, The University of Queensland, South Brisbane, QLD, Australia
| | - Emily S Dorey
- Mater Research Institute, The University of Queensland, South Brisbane, QLD, Australia
| | - Thomas Mullins
- Mater Research Institute, The University of Queensland, South Brisbane, QLD, Australia
| | - Josephine Laurie
- Obstetric Medicine, Mater Health, South Brisbane, QLD, Australia
| | - Marloes Dekker Nitert
- School of Chemistry and Molecular Biosciences, The University of Queensland, St Lucia, QLD 4072, Australia
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Sato S, Iino C, Furusawa K, Yoshida K, Chinda D, Sawada K, Mikami T, Nakaji S, Fukuda S, Sakuraba H. Effect of Oral Microbiota Composition on Metabolic Dysfunction-Associated Steatotic Liver Disease in the General Population. J Clin Med 2025; 14:2013. [PMID: 40142822 PMCID: PMC11943242 DOI: 10.3390/jcm14062013] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/05/2025] [Revised: 02/24/2025] [Accepted: 03/14/2025] [Indexed: 03/28/2025] Open
Abstract
Background/Objective: This study investigated the relationship between the composition of oral microbiota and metabolic dysfunction-associated steatotic liver disease (MASLD) in the general population. Methods: In total, 712 participants in a health check-up project were divided into four oral microbiota patterns by principal component analysis and cluster analysis; they were included in Neisseria, Streptococcus, Fusobacterium, and Veillonella groups. The Neisseria group had the largest number of patients and was used as a reference group to compare the incidence of MASLD and cardiometabolic criteria with the other groups. Results: In a multivariate analysis, the Veillonella group was a risk factor for MASLD independent of cardiometabolic criteria compared with the Neisseria group. The correlation between oral bacterial species and MASLD-related items showed that Neisseria was negatively correlated with controlled attenuation parameters, body mass index, waist circumference, hemoglobin A1c, alanine aminotransferase, and fatty liver index. Veillonella showed a positive correlation with controlled attenuation parameters, waist circumference, body mass index, blood pressure, triglycerides, alanine aminotransferase, aspartate aminotransferase, gamma-glutamyl transpeptidase, and fatty liver index, and a negative correlation with high-density lipoprotein cholesterol. In contrast, the Streptococcus and Fusobacterium groups were not clearly associated with MASLD. Conclusions: Maintaining oral hygiene and preventing periodontitis may contribute to preventing MASLD and extending a healthy lifespan.
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Affiliation(s)
- Satoshi Sato
- Department of Gastroenterology, Hematology, and Clinical Immunology, Hirosaki University Graduate School of Medicine, Hirosaki 036-8562, Japan
| | - Chikara Iino
- Department of Gastroenterology, Hematology, and Clinical Immunology, Hirosaki University Graduate School of Medicine, Hirosaki 036-8562, Japan
| | - Keisuke Furusawa
- Department of Gastroenterology, Hematology, and Clinical Immunology, Hirosaki University Graduate School of Medicine, Hirosaki 036-8562, Japan
| | - Kenta Yoshida
- Department of Gastroenterology, Hematology, and Clinical Immunology, Hirosaki University Graduate School of Medicine, Hirosaki 036-8562, Japan
| | - Daisuke Chinda
- Division of Endoscopy, Hirosaki University Graduate School of Medicine, Hirosaki 036-8562, Japan
| | - Kaori Sawada
- Department of Preemptive Medicine, Hirosaki University Graduate School of Medicine, Hirosaki 036-8562, Japan
| | - Tatsuya Mikami
- Department of Preemptive Medicine, Hirosaki University Graduate School of Medicine, Hirosaki 036-8562, Japan
| | - Shigeyuki Nakaji
- Department of Preemptive Medicine, Hirosaki University Graduate School of Medicine, Hirosaki 036-8562, Japan
| | - Shinsaku Fukuda
- Department of Gastroenterology, Hematology, and Clinical Immunology, Hirosaki University Graduate School of Medicine, Hirosaki 036-8562, Japan
| | - Hirotake Sakuraba
- Department of Gastroenterology, Hematology, and Clinical Immunology, Hirosaki University Graduate School of Medicine, Hirosaki 036-8562, Japan
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Choi YJ, Park J, Shin MG, Jung BK, Shin H, Cho S, Cho HI, Nah EH. Distribution and Characteristics of Oral Pathogens According to Blood Glucose Levels in South Korean Health Examinees. Int J Mol Sci 2025; 26:2638. [PMID: 40141280 PMCID: PMC11942294 DOI: 10.3390/ijms26062638] [Citation(s) in RCA: 1] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/04/2025] [Revised: 03/05/2025] [Accepted: 03/12/2025] [Indexed: 03/28/2025] Open
Abstract
The distribution of oral pathogens is influenced by genetic background, diet, socioeconomic status, and racial factors. This study aimed to assess the distribution and characteristics of oral pathogens based on blood glucose levels in a South Korean population. This cross-sectional, retrospective study included subjects from 17 health promotion centers in 13 South Korean cities between November 2021 and December 2022. Real-time multiplex PCR was used to detect 10 periodontitis-related pathogens, 6 dental caries-related pathogens, and 1 dental caries-protective bacterium. The most prevalent periodontitis-related pathogens were Parvimonas micra (97.6%), Porphyromonas endodontalis (96.8%), and Treponema socranskii (95.0%). Among dental caries-related pathogens, Streptococcus sanguinis and Veillonella parvula were found in all subjects. The prevalence of periodontitis-related pathogens was higher in males, while pathogens related to periodontitis and dental caries were more prevalent in older individuals. In the diabetes group, Aggregatibacter actinomycetemcomitans, red and orange complexes, and Streptococcus mutans were more prevalent. The relative amount of S. sanguinis was lower, while V. parvula was higher in individuals with diabetes mellitus. The prevalence and composition of oral pathogens vary by sex, age, and blood glucose levels. Diabetic individuals showed a pathogenic community structure linked to increased risks of periodontitis and dental caries.
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Affiliation(s)
- Yong Jun Choi
- Department of Laboratory Medicine, Chonnam National University Hwasun Hospital, Hwasun 58128, Republic of Korea; (Y.J.C.); (M.G.S.)
| | - Jooheon Park
- Department of Laboratory Medicine, Chonnam National University Hwasun Hospital, Hwasun 58128, Republic of Korea; (Y.J.C.); (M.G.S.)
| | - Myung Geun Shin
- Department of Laboratory Medicine, Chonnam National University Hwasun Hospital, Hwasun 58128, Republic of Korea; (Y.J.C.); (M.G.S.)
| | - Bong-Kwang Jung
- MEDIcheck Research Institute, Korea Association of Health Promotion, Seoul 07572, Republic of Korea; (B.-K.J.); (H.S.); (S.C.)
| | - Hyejoo Shin
- MEDIcheck Research Institute, Korea Association of Health Promotion, Seoul 07572, Republic of Korea; (B.-K.J.); (H.S.); (S.C.)
| | - Seon Cho
- MEDIcheck Research Institute, Korea Association of Health Promotion, Seoul 07572, Republic of Korea; (B.-K.J.); (H.S.); (S.C.)
| | - Han-Ik Cho
- MEDIcheck LAB, Korea Association of Health Promotion, Seoul 07572, Republic of Korea;
| | - Eun-Hee Nah
- Department of Laboratory Medicine, Chonnam National University Hwasun Hospital, Hwasun 58128, Republic of Korea; (Y.J.C.); (M.G.S.)
- Department of Laboratory Medicine, Chonnam National University Hospital, Gwangju 61469, Republic of Korea
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Arishi RA, Gridneva Z, Perrella SL, Cheema AS, Lai CT, Payne MS, Geddes DT, Stinson LF. Breastfeeding patterns and total volume of human milk consumed influence the development of the infant oral microbiome. J Oral Microbiol 2025; 17:2469892. [PMID: 40013012 PMCID: PMC11864009 DOI: 10.1080/20002297.2025.2469892] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/22/2024] [Revised: 01/23/2025] [Accepted: 02/14/2025] [Indexed: 02/28/2025] Open
Abstract
Background The oral microbiome of breastfed infants is distinct from that of formula-fed infants. However, breastfeeding characteristics, such as time spent breastfeeding (min/24 h), breastfeeding frequency (number of breastfeeds per day), and human milk intake (ml/day) vary significantly between breastfeeding dyads. Objectives Given that human milk and breastfeeding exposures likely influence early colonisation of the infant oral microbiome, this study aimed to elucidate the impact of breastfeeding characteristics on the development of the infant oral microbiome. Materials and methods Oral swabs (n = 55) were collected from infants at three months of age, alongside breastfeeding data collected over a 24-hour period. Bacterial DNA profiles were analysed using full-length 16S rRNA gene sequencing. Results Variations in breastfeeding characteristics contributed to differences in microbial community structure. Total breastfeeding duration (min/24 h) was positively associated with Bifidobacterium longum and Lactobacillus gasseri, while breastfeeding frequency was negatively associated with Veillonella sp. Additionally, human milk intake (ml/24 h) was negatively associated with Streptococcus parasanguinis. Conclusion These findings underscore the significant influence of early life feeding practices on oral microbial communities and emphasise the importance role of breastfeeding in shaping the oral microbiome during early life.
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Affiliation(s)
- Roaa A. Arishi
- School of Molecular Sciences, The University of Western Australia, Crawley, WA, Australia
- School of Molecular Sciences, ABREAST Network, Perth, WA, Australia
- School of Molecular Sciences, UWA Centre for Human Lactation Research and Translation, Crawley, WA, Australia
- Ministry of Education, Riyadh, Saudi Arabia
| | - Zoya Gridneva
- School of Molecular Sciences, The University of Western Australia, Crawley, WA, Australia
- School of Molecular Sciences, ABREAST Network, Perth, WA, Australia
- School of Molecular Sciences, UWA Centre for Human Lactation Research and Translation, Crawley, WA, Australia
| | - Sharon L. Perrella
- School of Molecular Sciences, The University of Western Australia, Crawley, WA, Australia
- School of Molecular Sciences, ABREAST Network, Perth, WA, Australia
- School of Molecular Sciences, UWA Centre for Human Lactation Research and Translation, Crawley, WA, Australia
| | - Ali S. Cheema
- The Kids Research Institute Australia, Nedlands, WA, Australia
| | - Ching T. Lai
- School of Molecular Sciences, The University of Western Australia, Crawley, WA, Australia
- School of Molecular Sciences, ABREAST Network, Perth, WA, Australia
- School of Molecular Sciences, UWA Centre for Human Lactation Research and Translation, Crawley, WA, Australia
| | - Matthew S. Payne
- Division of Obstetrics and Gynaecology, The University of Western Australia, Crawley, WA, Australia
| | - Donna T. Geddes
- School of Molecular Sciences, The University of Western Australia, Crawley, WA, Australia
- School of Molecular Sciences, ABREAST Network, Perth, WA, Australia
- School of Molecular Sciences, UWA Centre for Human Lactation Research and Translation, Crawley, WA, Australia
| | - Lisa F. Stinson
- School of Molecular Sciences, The University of Western Australia, Crawley, WA, Australia
- School of Molecular Sciences, ABREAST Network, Perth, WA, Australia
- School of Molecular Sciences, UWA Centre for Human Lactation Research and Translation, Crawley, WA, Australia
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7
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Luo Q, Chu S, Wu Y, Jin L, Liu R, Xu Y, Yu Y, Jin Y, Houndekon LOEP, Hu H, Zou Y, Huang H, Chen H. Characteristics of tongue coating microbiota in diabetic and non-diabetic kidney patients receiving hemodialysis. BMC Oral Health 2025; 25:104. [PMID: 39833942 PMCID: PMC11748270 DOI: 10.1186/s12903-025-05455-y] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/08/2024] [Accepted: 01/09/2025] [Indexed: 01/22/2025] Open
Abstract
BACKGROUND Tongue-coating microbiota, especially known as the tongue microbiome, holds significant value as both a prospective clinical diagnostic biomarker and therapeutic target, which plays a crucial role in the oral microecological health. However, there is limited understanding of the composition and function of tongue coating microbiota in chronic kidney disease patients undergoing hemodialysis. METHODS Thirty-one non-diabetic hemodialysis patients (nonDM_HD), 29 diabetic hemodialysis patients (DM_HD) and 33 healthy controls (HC) were enrolled. Swabs from tongue coating were collected. The 16S rDNA (V3-V4 region) was sequenced to scrutinize the tongue-coating bacterial microbiome difference. RESULTS Both nonDM_HD and DM_HD showed distinct bacterial communities of oral microbiota compared to HC. The abundance of Streptococcus, Lactobacillus, Ruminococcaceae G1, Ligilactobacillus and Abiotrophia showed a significant increase (p < 0.05) in DM_HD and nonDM_HD compared to HC, while Haemophilus, Lachnoanaerobaculum, Peptostreptococcaceae G1, Peptostreptococcus showed a significant decrease (p < 0.05) respectively. Veillonella, Lactobacillus, Limosilactobacillus etc. may serve as potential biomarkers for DM_HD. While Streptococcus, Ruminococcaceae G1, Actinobacillus, Abiotrophia can be considered alternative biomarkers for nonDM_HD. Moreover, the enriched Haemophilus, Actinomyces, Lachnoanaerobaculum were prominent features of the tongue coating microbiota in HC, which could be used as the potential therapeutic targets of chronic kidney disease. Network analysis revealed a less complex interaction relationship among the tongue coating bacterial microbiota of nonDM_HD and DM_HD. Furthermore, correlations were identified between the microbiome composition and clinical parameters of the individuals. CONCLUSION In conclusion, deciphering the tongue coating microbiota of kidney patients undergoing hemodialysis will helpful in assessing the role of oral microbiota in pathobiology and development of kidney disease, which is expected to become a potential biomarkers and adjuvant therapeutic target.
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Affiliation(s)
- Qiang Luo
- Department of Stomatology, The First Affiliated Hospital of Zhejiang Chinese Medical University, Zhejiang Provincial Hospital of Chinese Medicine, Hangzhou, 310006, China
| | - Siyuan Chu
- College of Life Sciences and Medicine, Zhejiang Sci-Tech University, Hangzhou, 310018, China
| | - Yongqun Wu
- College of Life Sciences and Medicine, Zhejiang Sci-Tech University, Hangzhou, 310018, China
| | - Lingling Jin
- Department of Stomatology, The First Affiliated Hospital of Zhejiang Chinese Medical University, Zhejiang Provincial Hospital of Chinese Medicine, Hangzhou, 310006, China
| | - Rui Liu
- Department of Stomatology, The First Affiliated Hospital of Zhejiang Chinese Medical University, Zhejiang Provincial Hospital of Chinese Medicine, Hangzhou, 310006, China
| | - Yulin Xu
- Department of Stomatology, The First Affiliated Hospital of Zhejiang Chinese Medical University, Zhejiang Provincial Hospital of Chinese Medicine, Hangzhou, 310006, China
| | - Yina Yu
- Department of Stomatology, The First Affiliated Hospital of Zhejiang Chinese Medical University, Zhejiang Provincial Hospital of Chinese Medicine, Hangzhou, 310006, China
| | - Yawei Jin
- Department of Stomatology, The First Affiliated Hospital of Zhejiang Chinese Medical University, Zhejiang Provincial Hospital of Chinese Medicine, Hangzhou, 310006, China
| | | | - Heshen Hu
- College of Life Sciences and Medicine, Zhejiang Sci-Tech University, Hangzhou, 310018, China
| | - Yvchen Zou
- College of Life Sciences and Medicine, Zhejiang Sci-Tech University, Hangzhou, 310018, China
| | - Hao Huang
- Department of Stomatology, The First Affiliated Hospital of Zhejiang Chinese Medical University, Zhejiang Provincial Hospital of Chinese Medicine, Hangzhou, 310006, China.
| | - Haimin Chen
- College of Life Sciences and Medicine, Zhejiang Sci-Tech University, Hangzhou, 310018, China.
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Tseng YC, Liao KS, Lin WT, Li C, Chang CB, Hsu JW, Chan CP, Chen CM, Wang HP, Chien HC, Wang JT, Hsieh SC, Wu SF. A human oral commensal-mediated protection against Sjögren's syndrome with maintenance of T cell immune homeostasis and improved oral microbiota. NPJ Biofilms Microbiomes 2025; 11:18. [PMID: 39820778 PMCID: PMC11739518 DOI: 10.1038/s41522-025-00654-5] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/21/2024] [Accepted: 01/07/2025] [Indexed: 01/19/2025] Open
Abstract
Sjögren's syndrome (SS) is a prevalent systemic autoimmune disease with substantial impacts on women's health worldwide. Although oral Haemophilus parainfluenzae is reduced in SS, its significance remains unclear. This study aimed to elucidate the pathophysiological role of H. parainfluenzae in SS. Reduced salivary H. parainfluenzae levels in SS patients were confirmed through quantitative PCR. Oral H. parainfluenzae inoculation in NOD mice alleviated focal sialadenitis, improved salivary function, and reduced IFN-γ+CD3+ and IFN-γ+CD8+ T cells in salivary gland-draining lymph nodes, maintaining immune homeostasis against a biased type 1 response. Inoculation also enhanced salivary microbiota diversity, balanced the Firmicutes-to-Proteobacteria ratio, and reduced the overwhelming presence of Pseudomonas mendocina. In vitro, H. parainfluenzae-preconditioned A253 cells limited CD8 T cell expansion with reduced IFN-γ production. These findings suggest that H. parainfluenzae improves oral microbial diversity, promotes homeostatic T-cell immunity, and protects against SS, supporting its potential as a next-generation probiotic.
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Affiliation(s)
- Yu-Chao Tseng
- Division of Allergy, Immunology, and Rheumatology, Department of Internal Medicine, Ditmanson Medical Foundation Chia-Yi Christian Hospital, Chiayi, Taiwan
- Department of Medical Research, Ditmanson Medical Foundation Chia-Yi Christian Hospital, Chiayi, Taiwan
- Department of Biomedical Sciences and Institute of Molecular Biology, National Chung Cheng University, Chiayi, Taiwan
| | - Kai-Sheng Liao
- Department of Pathology, Ditmanson Medical Foundation Chia-Yi Christian Hospital, Chiayi, Taiwan
| | - Wei-Ting Lin
- Department Oral and Maxillofacial Surgery, Ditmanson Medical Foundation Chia-Yi Christian Hospital, Chiayi, Taiwan
| | - Chin Li
- Department of Biomedical Sciences and Institute of Molecular Biology, National Chung Cheng University, Chiayi, Taiwan
| | - Chia-Bin Chang
- Department of Urology, Ditmanson Medical Foundation Chia-Yi Christian Hospital, Chiayi, Taiwan
| | - Jie-Wei Hsu
- Department of Biomedical Sciences and Institute of Molecular Biology, National Chung Cheng University, Chiayi, Taiwan
| | - Chin-Pui Chan
- Department of Biomedical Sciences and Institute of Molecular Biology, National Chung Cheng University, Chiayi, Taiwan
| | - Chun-Ming Chen
- Division of Allergy, Immunology, and Rheumatology, Department of Internal Medicine, Ditmanson Medical Foundation Chia-Yi Christian Hospital, Chiayi, Taiwan
| | - Hon-Pin Wang
- Division of Allergy, Immunology, and Rheumatology, Department of Internal Medicine, Ditmanson Medical Foundation Chia-Yi Christian Hospital, Chiayi, Taiwan
| | - Hsiu-Chuan Chien
- Department of Laboratory Medicine, Ditmanson Medical Foundation Chia-Yi Christian Hospital, Chiayi, Taiwan
| | - Jann-Tay Wang
- Department of Internal Medicine, National Taiwan University Hospital, Taipei, Taiwan
| | - Song-Chou Hsieh
- Department of Internal Medicine, National Taiwan University Hospital, Taipei, Taiwan.
| | - Shu-Fen Wu
- Department of Biomedical Sciences and Institute of Molecular Biology, National Chung Cheng University, Chiayi, Taiwan.
- Epigenomics and Human Diseases Research Center, National Chung Cheng University, Chiayi, Taiwan.
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Samodova D, Stankevic E, Søndergaard MS, Hu N, Ahluwalia TS, Witte DR, Belstrøm D, Lubberding AF, Jagtap PD, Hansen T, Deshmukh AS. Salivary proteomics and metaproteomics identifies distinct molecular and taxonomic signatures of type-2 diabetes. MICROBIOME 2025; 13:5. [PMID: 39794871 PMCID: PMC11720885 DOI: 10.1186/s40168-024-01997-5] [Citation(s) in RCA: 2] [Impact Index Per Article: 2.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Subscribe] [Scholar Register] [Received: 05/03/2024] [Accepted: 12/04/2024] [Indexed: 01/13/2025]
Abstract
BACKGROUND Saliva is a protein-rich body fluid for noninvasive discovery of biomolecules, containing both human and microbial components, associated with various chronic diseases. Type-2 diabetes (T2D) imposes a significant health and socio-economic burden. Prior research on T2D salivary microbiome utilized methods such as metagenomics, metatranscriptomics, 16S rRNA sequencing, and low-throughput proteomics. RESULTS We conducted ultrafast, in-depth MS-based proteomic and metaproteomic profiling of saliva from 15 newly diagnosed T2D individuals and 15 age-/BMI-matched healthy controls (HC). Using state-of-the-art proteomics, over 4500 human and bacterial proteins were identified in a single 21-min run. Bioinformatic analysis revealed host signatures of altered immune-, lipid-, and glucose-metabolism regulatory systems, increased oxidative stress, and possible precancerous changes in T2D saliva. Abundance of peptides for bacterial genera such as Neisseria and Corynebacterium were altered showing biomarker potential, offering insights into disease pathophysiology and microbial applications for T2D management. CONCLUSIONS This study presents a comprehensive mapping of salivary proteins and microbial communities, serving as a foundational resource for enhancing understanding of T2D pathophysiology. The identified biomarkers hold promise for advancing diagnostics and therapeutic approaches in T2D and its associated long-term complication Video Abstract.
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Affiliation(s)
- Diana Samodova
- Novo Nordisk Foundation Center for Basic Metabolic Research, University of Copenhagen, Blegdamsvej 3B, Copenhagen, 2200, Denmark
| | - Evelina Stankevic
- Novo Nordisk Foundation Center for Basic Metabolic Research, University of Copenhagen, Blegdamsvej 3B, Copenhagen, 2200, Denmark
| | | | - Naiyu Hu
- Novo Nordisk Foundation Center for Basic Metabolic Research, University of Copenhagen, Blegdamsvej 3B, Copenhagen, 2200, Denmark
| | - Tarunveer S Ahluwalia
- Steno Diabetes Center Copenhagen, Borgmester Ib Juuls Vej 83, Herlev, 2730, Denmark
- Department of Biology, The Bioinformatics Center, University of Copenhagen, Ole Maaløes Vej 5, Copenhagen, 2200, Denmark
| | - Daniel R Witte
- Department of Public Health, Aarhus University, Bartholins Allé 2, Building 1260, Aarhus, 8000, Denmark
- Steno Diabetes Center Aarhus, Aarhus University Hospital, Palle Juul-Jensens, Boulevard 11, Entrance A, Aarhus, 8200, Denmark
| | - Daniel Belstrøm
- Section for Clinical Oral Microbiology, Department of Odontology, University of Copenhagen, Nørre Allé 20, Copenhagen, 2200, Denmark
| | | | - Pratik D Jagtap
- Department of Biochemistry, Molecular Biology, and Biophysics, University of Minnesota, 420 Washington Ave SE, Minneapolis, MN, 55455, USA
| | - Torben Hansen
- Novo Nordisk Foundation Center for Basic Metabolic Research, University of Copenhagen, Blegdamsvej 3B, Copenhagen, 2200, Denmark.
| | - Atul S Deshmukh
- Novo Nordisk Foundation Center for Basic Metabolic Research, University of Copenhagen, Blegdamsvej 3B, Copenhagen, 2200, Denmark.
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Xu Q, Wang W, Li Y, Cui J, Zhu M, Liu Y, Liu Y. The oral-gut microbiota axis: a link in cardiometabolic diseases. NPJ Biofilms Microbiomes 2025; 11:11. [PMID: 39794340 PMCID: PMC11723975 DOI: 10.1038/s41522-025-00646-5] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/18/2024] [Accepted: 12/29/2024] [Indexed: 01/13/2025] Open
Abstract
The oral-gut microbiota axis plays a crucial role in cardiometabolic health. This review explores the interactions between these microbiomes through enteric, hematogenous, and immune pathways, resulting in disruptions in microbial balance and metabolic processes. These disruptions contribute to systemic inflammation, metabolic disorders, and endothelial dysfunction, which are closely associated with cardiometabolic diseases. Understanding these interactions provides insights for innovative therapeutic strategies to prevent and manage cardiometabolic diseases.
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Affiliation(s)
- Qian Xu
- National Clinical Research Center for TCM Cardiology, Xiyuan Hospital of China Academy of Chinese Medical Sciences, 100091, Beijing, China
| | - Wenting Wang
- National Clinical Research Center for TCM Cardiology, Xiyuan Hospital of China Academy of Chinese Medical Sciences, 100091, Beijing, China
| | - Yiwen Li
- National Clinical Research Center for TCM Cardiology, Xiyuan Hospital of China Academy of Chinese Medical Sciences, 100091, Beijing, China
| | - Jing Cui
- National Clinical Research Center for TCM Cardiology, Xiyuan Hospital of China Academy of Chinese Medical Sciences, 100091, Beijing, China
| | - Mengmeng Zhu
- National Clinical Research Center for TCM Cardiology, Xiyuan Hospital of China Academy of Chinese Medical Sciences, 100091, Beijing, China
| | - Yanfei Liu
- National Clinical Research Center for TCM Cardiology, Xiyuan Hospital of China Academy of Chinese Medical Sciences, 100091, Beijing, China
- The Second Department of Geriatrics, Xiyuan Hospital of China Academy of Chinese Medical Sciences, 100091, Beijing, China
- Key Laboratory of Disease and Syndrome Integration Prevention and Treatment of Vascular Aging, Xiyuan Hospital of China Academy of Chinese Medical Sciences, 100091, Beijing, China
| | - Yue Liu
- National Clinical Research Center for TCM Cardiology, Xiyuan Hospital of China Academy of Chinese Medical Sciences, 100091, Beijing, China.
- Key Laboratory of Disease and Syndrome Integration Prevention and Treatment of Vascular Aging, Xiyuan Hospital of China Academy of Chinese Medical Sciences, 100091, Beijing, China.
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11
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Vieira Lima CP, Pauletto P, Lataro RM, De Luca Canto G, Dame-Teixeira N, Stefani CM. The Oral Microbiome in Diabetes, Arterial Hypertension, and Obesity: A Scoping Review. ADVANCES IN EXPERIMENTAL MEDICINE AND BIOLOGY 2025; 1472:201-223. [PMID: 40111694 DOI: 10.1007/978-3-031-79146-8_13] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Subscribe] [Scholar Register] [Indexed: 03/22/2025]
Abstract
BACKGROUND Changes in the oral microbiome are expected in the presence of chronic conditions such as type 2 diabetes mellitus (T2D), arterial hypertension (AH), and obesity (OB). OBJECTIVE We aimed to map the literature regarding oral microbiome changes in people with T2D, AH, or OB compared to those without these conditions. METHODS This scoping review was guided by the JBI Manual for Evidence Synthesis and reported according to the PRISMA extension for scoping reviews (PRISMA-ScR). A search strategy was developed and adapted to five databases (Embase, LILACS, PubMed, Scopus, and Web of Science) and gray literature (Google Scholar and ProQuest Dissertation and Thesis). Two reviewers individually screened studies for inclusion. Data from the studies, including the molecular method to evaluate the microbiome and the type of sample, were extracted and analyzed. The focus was significant changes in phylum and genera. RESULTS A total of 1413 records were retrieved from databases, 86 from gray literature, and 7 from reference lists. After the screening process, 50 records were included, 28 on T2D, 8 on AH, and 12 on OB. Two studies addressed metabolic syndromes. Most studies identified the oral microbiome in saliva using 16S rRNA amplicon sequencing. CONCLUSION At the phylum level, Fusobacteria was enriched in ≥3 studies in people with T2D. Firmicutes enrichment was associated with T2D and OB. Genera enriched in T2D comprised Catonella, Leptotrichia, Prevotella, and Rothia. Aggregatibacter and Prevotella were enriched in OB. No phylum or genera were consistently enriched in AH.OSF protocol registration: DOI 10.17605/OSF.IO/XK72V (available at https://osf.io/z5fp4 ).
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Affiliation(s)
| | | | | | - Graziela De Luca Canto
- Federal University of Santa Catarina - UFSC, Florianopolis, Brazil
- Brazilian Centre for Evidence-Based Research (COBE), Florianopolis, Brazil
| | | | - Cristine Miron Stefani
- University of Brasília, Brasília, Brazil.
- Brazilian Centre for Evidence-Based Research (COBE), Florianopolis, Brazil.
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12
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Yin Y, Yang T, Tian Z, Shi C, Yan C, Li H, Du Y, Li G. Progress in the investigation of the Firmicutes/Bacteroidetes ratio as a potential pathogenic factor in ulcerative colitis. J Med Microbiol 2025; 74. [PMID: 39886918 DOI: 10.1099/jmm.0.001966] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 02/01/2025] Open
Abstract
Ulcerative colitis (UC) is a chronic inflammatory bowel disease (IBD) that presents significant challenges in terms of treatment owing to a pronounced likelihood of recurrence and an elevated risk of cancer development, thereby imposing substantial risks on affected individuals. The gut microbiota of Firmicutes and Bacteroidetes (F/B) can affect diseases associated with IBD, which is also a risk factor for breast cancer. This review discusses the hazards associated with UC, highlights the existing disparities in UC-associated gut microbiome research, explores the concept of the F/B ratio and scrutinizes its correlation with UC. Moreover, the differences in the F/B ratios between healthy individuals and those with UC were thoroughly examined. These findings suggest that an elevated F/B ratio may promote the occurrence and progression of UC. Consequently, the F/B ratio may play a significant role in UC by influencing gut microbiota composition and inflammatory responses, suggesting that future research should focus on this ratio as a potential biomarker for disease progression and therapeutic targets in managing UC.
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Affiliation(s)
- Yu Yin
- The Affiliated Hospital of Changchun University of Chinese Medicine, Changchun 130117, PR China
| | - Tiezheng Yang
- The Affiliated Hospital of Changchun University of Chinese Medicine, Changchun 130117, PR China
| | - Ziyue Tian
- Hainan Provincial People's Hospital, Haikou 570100, PR China
| | - Chong Shi
- The Affiliated Hospital of Changchun University of Chinese Medicine, Changchun 130117, PR China
| | - Chengqiu Yan
- The Affiliated Hospital of Changchun University of Chinese Medicine, Changchun 130117, PR China
| | - Hui Li
- The Affiliated Hospital of Changchun University of Chinese Medicine, Changchun 130117, PR China
| | - Yu Du
- The Affiliated Hospital of Changchun University of Chinese Medicine, Changchun 130117, PR China
| | - Guofeng Li
- Shenzhen Bao'an Authentic TCM Therapy Hospital, Shenzhen 518000, PR China
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13
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Tang L, Ding K, Li M, Chao X, Sun T, Guo Y, Peng X, Jia W, Chen T, Xie G, Feng L. Differences in oral microbiota associated with type 2 diabetes mellitus between the Dai and Han populations. J Oral Microbiol 2024; 17:2442420. [PMID: 39763576 PMCID: PMC11703080 DOI: 10.1080/20002297.2024.2442420] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/13/2024] [Revised: 12/02/2024] [Accepted: 12/04/2024] [Indexed: 01/04/2025] Open
Abstract
BACKGROUND Type 2 diabetes mellitus (T2DM) development is closely linked to microbiota, influenced by geography, ethnicity, gender, and age. While the relationship between oral microbiota and T2DM has been explored, specific microbiota associated with T2DM in the Dai and Han populations remains unclear. This study aims to compare oral microbiota differences and identify keystone species between these populations, both with and without T2DM. METHODS We recruited 28 han participants (6 healthy children, 10 healthy adults, 12 adults with T2DM) and 34 Dai participants (11 healthy children, 10 healthy adults, 13 adults with T2DM). Blood samples were collected for biochemical analysis, and saliva samples underwent DNA extraction and 16S rRNA sequencing. RESULTS Age significantly influenced oral microbiota differences between the Dai and Han populations, overshadowing the effects of diabetes. In the Dai population with T2DM, notable increases in Alistipes putredinis, Lactobacillus spp., Faecalibacterium prausnitzii, and Akkermansia muciniphila were observed compared to the Han population. Keystone genera differed, with Fusibacter central to the Dai population's microbial network, while the Han network was more scattered. CONCLUSION This is the first comparative analysis of oral microbiota in the Dai and Han populations with T2DM, highlighting age and ethnicity's influence on microbial composition.
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Affiliation(s)
- Lingtong Tang
- Department of Clinical Laboratory, The People’s Hospital of Gao County, Yibin, Sichuan, China
- Department of Clinical Laboratory, Yan’an Hospital Affiliated to Kunming Medical University, Kunming, China
| | - Keke Ding
- Center for Translational Medicine and Shanghai Key Laboratory of Diabetes Mellitus, Shanghai Sixth People’s Hospital Affiliated to Shanghai Jiao Tong University School of Medicine, Shanghai, China
| | - Mengci Li
- Center for Translational Medicine and Shanghai Key Laboratory of Diabetes Mellitus, Shanghai Sixth People’s Hospital Affiliated to Shanghai Jiao Tong University School of Medicine, Shanghai, China
| | - Xiaowen Chao
- Center for Translational Medicine and Shanghai Key Laboratory of Diabetes Mellitus, Shanghai Sixth People’s Hospital Affiliated to Shanghai Jiao Tong University School of Medicine, Shanghai, China
| | - Tao Sun
- Center for Translational Medicine and Shanghai Key Laboratory of Diabetes Mellitus, Shanghai Sixth People’s Hospital Affiliated to Shanghai Jiao Tong University School of Medicine, Shanghai, China
| | - Yuhuai Guo
- Center for Translational Medicine and Shanghai Key Laboratory of Diabetes Mellitus, Shanghai Sixth People’s Hospital Affiliated to Shanghai Jiao Tong University School of Medicine, Shanghai, China
| | - Xufei Peng
- Center for Translational Medicine and Shanghai Key Laboratory of Diabetes Mellitus, Shanghai Sixth People’s Hospital Affiliated to Shanghai Jiao Tong University School of Medicine, Shanghai, China
| | - Wei Jia
- Center for Translational Medicine and Shanghai Key Laboratory of Diabetes Mellitus, Shanghai Sixth People’s Hospital Affiliated to Shanghai Jiao Tong University School of Medicine, Shanghai, China
- Department of Pharmacology and Pharmacy, University of Hong Kong, Hong Kong, China
| | - Tianlu Chen
- Center for Translational Medicine and Shanghai Key Laboratory of Diabetes Mellitus, Shanghai Sixth People’s Hospital Affiliated to Shanghai Jiao Tong University School of Medicine, Shanghai, China
| | - Guoxiang Xie
- Human Metabolomics Institute Inc, Shenzhen, China
| | - Lei Feng
- Department of Clinical Laboratory, Yan’an Hospital Affiliated to Kunming Medical University, Kunming, China
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Guan H, Zhao S, Tan Y, Fang X, Zhang Y, Zhang Y, Miao R, Yin R, Yao Y, Tian J. Microbiomic insights into the oral microbiome's role in type 2 diabetes mellitus: standardizing approaches for future advancements. Front Endocrinol (Lausanne) 2024; 15:1416611. [PMID: 39678196 PMCID: PMC11638674 DOI: 10.3389/fendo.2024.1416611] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 04/12/2024] [Accepted: 11/06/2024] [Indexed: 12/17/2024] Open
Abstract
The burgeoning field of microbiomics has unveiled significant insights into the role of the oral microbiome in the pathophysiology of Type 2 Diabetes Mellitus (T2DM), with this review focusing on recent advancements in diabetic oral microbiology, its clinical applications, and identifying factors that may affect study interpretations. A comprehensive review across various databases, including PubMed and Google Scholar, was conducted to collate original research data published in the past five years, specifically targeting studies exploring the impact of the oral microbiome on T2DM and emphasizing research that employs microbiomic approaches in clinical patient populations. The findings delineate the intricate interplay between T2DM and oral microbiome dysbiosis, highlighting significant microbial shifts following periodontal and antidiabetic treatments, and pointing to the complexity of the relationship between oral health and systemic disease. The observed oral microbial shifts in T2DM underscore the critical need for standardized research methodologies in microbiomic studies, suggesting that by adopting a unified approach, future research can more effectively elucidate the oral microbiome's role in T2DM. This could pave the way for innovative diagnostic and therapeutic strategies in managing T2DM and its oral health complications, thus making a pertinent overview of the work within the field.
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Affiliation(s)
- Huifang Guan
- College of Traditional Chinese Medicine, Changchun University of Chinese Medicine, Changchun, China
| | - Shuang Zhao
- College of Traditional Chinese Medicine, Changchun University of Chinese Medicine, Changchun, China
| | - Yuanfei Tan
- Department of Tuina, The Affiliated Hospital of Changchun University of Chinese Medicine, Changchun, China
| | - Xinyi Fang
- Institute of Metabolic Diseases, Guang’anmen Hospital, China Academy of Chinese Medical Sciences, Beijing, China
- Graduate College, Beijing University of Chinese Medicine, Beijing, China
| | - Yuxin Zhang
- Institute of Metabolic Diseases, Guang’anmen Hospital, China Academy of Chinese Medical Sciences, Beijing, China
| | - Yanjiao Zhang
- Institute of Metabolic Diseases, Guang’anmen Hospital, China Academy of Chinese Medical Sciences, Beijing, China
| | - Runyu Miao
- Institute of Metabolic Diseases, Guang’anmen Hospital, China Academy of Chinese Medical Sciences, Beijing, China
- Graduate College, Beijing University of Chinese Medicine, Beijing, China
| | - Ruiyang Yin
- Institute of Metabolic Diseases, Guang’anmen Hospital, China Academy of Chinese Medical Sciences, Beijing, China
| | - Yiqi Yao
- Institute of Metabolic Diseases, Guang’anmen Hospital, China Academy of Chinese Medical Sciences, Beijing, China
| | - Jiaxing Tian
- Institute of Metabolic Diseases, Guang’anmen Hospital, China Academy of Chinese Medical Sciences, Beijing, China
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15
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Talib N, Mohamad NE, Ho CL, Masarudin MJ, Alitheen NB. Modulatory Effects of Isolated Lactobacillus paracasei from Malaysian Water Kefir Grains on the Intestinal Barrier and Gut Microbiota in Diabetic Mice. Probiotics Antimicrob Proteins 2024:10.1007/s12602-024-10367-4. [PMID: 39313703 DOI: 10.1007/s12602-024-10367-4] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Accepted: 09/13/2024] [Indexed: 09/25/2024]
Abstract
Type 2 diabetes (T2DM) is one of the four major types of non-communicable diseases that have become a global health concern. Water kefir is a product of a brown sugar solution fermented with kefir grains which comprises around 30 microbial species in its grains. Water kefir possesses a wide range of health benefits, including anti-hyperlipidemic effects, and reduces hypertension and blood glucose levels in animal models. Reportedly, consuming water kefir containing probiotics may enhance the intestinal barrier and positively influence the composition of the intestinal microflora. The present study aimed to evaluate the regulatory effects of Lactobacillus paracasei isolated from Malaysian water kefir grains (MWKG) on the alterations of intestinal barrier and gut microbiota in diabetic mice via histopathological analysis of the distal colon and 16S rRNA gene sequencing on fecal microbiome. Results indicated that the administration of isolated Lactobacillus paracasei from MWKG to diabetic mice ameliorated the dominant probiotic phyla in the gut microbiota. Results showed that lower dose (LD) and high dose (HD) treatments of the isolated Lactobacillus paracasei could significantly reduce inflammatory cell infiltration in the distal colon of diabetic mice. The treatments revealed a significant decrease in the relative abundance of Firmicutes in the gut, 0.27 ± 0.06% for LD and 0.34 ± 0.04% for HD, compared to untreated (UN) diabetic mice, 0.40 ± 0.02%. These results suggest that L. paracasei isolated from MWKG could serve as a potential dietary supplement against intestinal inflammation and modify gut microbiota composition in patients with T2DM.
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Affiliation(s)
- Noorshafadzilah Talib
- Department of Cell and Molecular Biology, Faculty of Biotechnology and Biomolecular Sciences, Universiti Putra Malaysia, 43400 UPM, Serdang, Selangor Darul Ehsan, Malaysia
| | - Nurul Elyani Mohamad
- Biotechnology Research Institute, Universiti Malaysia Sabah, 88400, Kota Kinabalu, Sabah, Malaysia
| | - Chai Ling Ho
- Department of Cell and Molecular Biology, Faculty of Biotechnology and Biomolecular Sciences, Universiti Putra Malaysia, 43400 UPM, Serdang, Selangor Darul Ehsan, Malaysia
| | - Mas Jaffri Masarudin
- Department of Cell and Molecular Biology, Faculty of Biotechnology and Biomolecular Sciences, Universiti Putra Malaysia, 43400 UPM, Serdang, Selangor Darul Ehsan, Malaysia
- UPM-MAKNA Cancer Research Laboratory, Institute of Bioscience, Universiti Putra Malaysia, 43400 UPM, Serdang, Selangor Darul Ehsan, Malaysia
| | - Noorjahan Banu Alitheen
- Department of Cell and Molecular Biology, Faculty of Biotechnology and Biomolecular Sciences, Universiti Putra Malaysia, 43400 UPM, Serdang, Selangor Darul Ehsan, Malaysia.
- UPM-MAKNA Cancer Research Laboratory, Institute of Bioscience, Universiti Putra Malaysia, 43400 UPM, Serdang, Selangor Darul Ehsan, Malaysia.
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16
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Lyu X, Xu X, Shen S, Qin F. Genetics causal analysis of oral microbiome on type 2 diabetes in East Asian populations: a bidirectional two-sample Mendelian randomized study. Front Endocrinol (Lausanne) 2024; 15:1452999. [PMID: 39247916 PMCID: PMC11380152 DOI: 10.3389/fendo.2024.1452999] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 06/22/2024] [Accepted: 08/06/2024] [Indexed: 09/10/2024] Open
Abstract
Introduction The dysbiosis of the oral microbiome is associated with the progression of various systemic diseases, including diabetes. However, the precise causal relationships remain elusive. This study aims to investigate the potential causal associations between oral microbiome and type 2 diabetes (T2D) using Mendelian randomization (MR) analyses. Methods We conducted bidirectional two-sample MR analyses to investigate the impact of oral microbiome from saliva and the tongue T2D. This analysis was based on metagenome-genome-wide association studies (mgGWAS) summary statistics of the oral microbiome and a large meta-analysis of GWAS of T2D in East Asian populations. Additionally, we utilized the T2D GWAS summary statistics from the Biobank Japan (BBJ) project for replication. The MR methods employed included Wald ratio, inverse variance weighting (IVW), weighted median, MR-Egger, contamination mixture (ConMix), and robust adjusted profile score (RAPS). Results Our MR analyses revealed genetic associations between specific bacterial species in the oral microbiome of saliva and tongue with T2D in East Asian populations. The MR results indicated that nine genera were shared by both saliva and tongue. Among these, the genera Aggregatibacter, Pauljensenia, and Prevotella were identified as risk factors for T2D. Conversely, the genera Granulicatella and Haemophilus D were found to be protective elements against T2D. However, different species within the genera Catonella, Lachnoanaerobaculum, Streptococcus, and Saccharimonadaceae TM7x exhibited multifaceted influences; some species were positively correlated with the risk of developing T2D, while others were negatively correlated. Discussion This study utilized genetic variation tools to confirm the causal effect of specific oral microbiomes on T2D in East Asian populations. These findings provide valuable insights for the treatment and early screening of T2D, potentially informing more targeted and effective therapeutic strategies.
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Affiliation(s)
- Xinyi Lyu
- West China Medical School, West China Hospital, Sichuan University, Chengdu, Sichuan, China
| | - Xueyuan Xu
- West China Medical School, West China Hospital, Sichuan University, Chengdu, Sichuan, China
| | - Sihong Shen
- West China Medical School, West China Hospital, Sichuan University, Chengdu, Sichuan, China
| | - Feng Qin
- Department of Endocrinology and Andrology Laboratory, West China Hospital, Sichuan University, Chengdu, Sichuan, China
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17
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Wang J, Gu L, Zhi C, Yang S. Risk factor and prediction model development for severe radiation-induced oral mucositis in head and neck tumors. Future Oncol 2024; 20:2385-2395. [PMID: 39105623 PMCID: PMC11520562 DOI: 10.1080/14796694.2024.2384353] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/15/2024] [Accepted: 07/22/2024] [Indexed: 08/07/2024] Open
Abstract
Aim: This article aims to identify risk factors for severe radiation-induced oral mucositis (RIOM) in head and neck cancer (HNC) patients. In addition, we intend to establish a predictive model in patients undergoing intensity-modulated radiotherapy.Patients & methods: In this retrospective study, several HNC patients (n = 179) treated at Zhejiang Provincial People's Hospital from January 2019 to June 2023 were considered. The recruited subjects were divided into modeling and validation groups. The experimental data on clinical characteristics and treatment were collected and analyzed to identify predictive factors for severe RIOM based on the logistic regression approach.Results: The results indicated that severe RIOM occurred in 55.3% of patients. Accordingly, significant predictors included smoking history, diabetes, concurrent chemotherapy, cumulative radiation dose and weight loss of ≥5% in relative to admission weight. A nomogram based on these factors was validated, showing excellent predictive accuracy.Conclusion: In summary, the predictive model could effectively identify high-risk patients for severe RIOM, enabling the design of targeted interventions and improving patient management during radiotherapy.
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Affiliation(s)
- Jiajia Wang
- Otolaryngology & Head & Neck Center, Cancer Center, Department of Otolaryngology, Zhejiang Provincial People’s Hospital (Affiliated People’s Hospital, Hangzhou Medical College), Hangzhou, Zhejiang, 310014, China
| | - Liqiong Gu
- Center for General Practice Medicine, Department of Infectious Diseases, Zhejiang Provincial People’s Hospital (Affiliated People’s Hospital, Hangzhou Medical College), Hangzhou, Zhejiang, 310014, China
| | - Caixia Zhi
- Otolaryngology & Head & Neck Center, Cancer Center, Department of Otolaryngology, Zhejiang Provincial People’s Hospital (Affiliated People’s Hospital, Hangzhou Medical College), Hangzhou, Zhejiang, 310014, China
| | - Shujuan Yang
- Otolaryngology & Head & Neck Center, Cancer Center, Department of Otolaryngology, Zhejiang Provincial People’s Hospital (Affiliated People’s Hospital, Hangzhou Medical College), Hangzhou, Zhejiang, 310014, China
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Zeng X, Huang S, Ye X, Song S, He J, Hu L, Deng S, Liu F. Impact of HbA1c control and type 2 diabetes mellitus exposure on the oral microbiome profile in the elderly population. J Oral Microbiol 2024; 16:2345942. [PMID: 38756148 PMCID: PMC11097700 DOI: 10.1080/20002297.2024.2345942] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/03/2024] [Accepted: 04/18/2024] [Indexed: 05/18/2024] Open
Abstract
Objective To investigate the associations of the oral microbiome status with diabetes characteristics in elderly patients with type 2 diabetes mellitus. Methods A questionnaire was used to assess age, sex, smoking status, drinking status, flossing frequency, T2DM duration and complications, and a blood test was used to determine the glycated haemoglobin (HbA1c) level. Sequencing of the V3-V4 region of the 16S rRNA gene from saliva samples was used to analyze the oral microbiome. Results Differential analysis revealed that Streptococcus and Weissella were significantly enriched in the late-stage group, and Capnocytophaga was significantly enriched in the early-stage group. Correlation analysis revealed that diabetes duration was positively correlated with the abundance of Streptococcus (r= 0.369, p= 0.007) and negatively correlated with the abundance of Cardiobacterium (r= -0.337, p= 0.014), and the level of HbA1c was not significantly correlated with the oral microbiome. Network analysis suggested that the poor control group had a more complex microbial network than the control group, a pattern that was similar for diabetes duration. In addition, Streptococcus has a low correlation with other microorganisms. Conclusion In elderly individuals, Streptococcus emerges as a potential biomarker linked to diabetes, exhibiting elevated abundance in diabetic patients influenced by disease exposure and limited bacterial interactions.
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Affiliation(s)
- Xin Zeng
- West China School of Nursing, Sichuan University, Chengdu, China
| | - Shuqi Huang
- Nursing Department, State Key Laboratory of Oral Diseases & National Clinical Research Center for Oral Diseases, West China Hospital of Stomatology, Sichuan University, Chengdu, China
| | - Xin Ye
- West China School of Nursing, Sichuan University, Chengdu, China
| | - Siping Song
- Post anesthesia Care Unit, West China Hospital of Stomatology, Sichuan University, Chengdu, China
| | - Jing He
- Department of Oral Mucosal Diseases, West China Hospital of Stomatology, Sichuan University, Chengdu, China
| | - Liwei Hu
- Department of Oral Surgery, West China Hospital of Stomatology, Sichuan University, Chengdu, China
| | - Sicheng Deng
- West China School of Nursing, Sichuan University, Chengdu, China
| | - Fan Liu
- Nursing Department, State Key Laboratory of Oral Diseases & National Clinical Research Center for Oral Diseases, West China Hospital of Stomatology, Sichuan University, Chengdu, China
- Innovation Center of Nursing Research, Nursing Key Laboratory of Sichuan Province, Chengdu, China
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Arishi RA, Lai CT, Geddes DT, Stinson LF. Impact of breastfeeding and other early-life factors on the development of the oral microbiome. Front Microbiol 2023; 14:1236601. [PMID: 37744908 PMCID: PMC10513450 DOI: 10.3389/fmicb.2023.1236601] [Citation(s) in RCA: 2] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [Key Words] [Grants] [Track Full Text] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/08/2023] [Accepted: 08/25/2023] [Indexed: 09/26/2023] Open
Abstract
The oral cavity is home to the second most diverse microbiome in the human body. This community contributes to both oral and systemic health. Acquisition and development of the oral microbiome is a dynamic process that occurs over early life; however, data regarding longitudinal assembly of the infant oral microbiome is scarce. While numerous factors have been associated with the composition of the infant oral microbiome, early feeding practices (breastfeeding and the introduction of solids) appear to be the strongest determinants of the infant oral microbiome. In the present review, we draw together data on the maternal, infant, and environmental factors linked to the composition of the infant oral microbiome, with a focus on early nutrition. Given evidence that breastfeeding powerfully shapes the infant oral microbiome, the review explores potential mechanisms through which human milk components, including microbes, metabolites, oligosaccharides, and antimicrobial proteins, may interact with and shape the infant oral microbiome. Infancy is a unique period for the oral microbiome. By enhancing our understanding of oral microbiome assembly in early life, we may better support both oral and systemic health throughout the lifespan.
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Affiliation(s)
- Roaa A. Arishi
- School of Molecular Sciences, The University of Western Australia, Perth, WA, Australia
- Ministry of Health, Riyadh, Saudi Arabia
| | - Ching T. Lai
- School of Molecular Sciences, The University of Western Australia, Perth, WA, Australia
| | - Donna T. Geddes
- School of Molecular Sciences, The University of Western Australia, Perth, WA, Australia
| | - Lisa F. Stinson
- School of Molecular Sciences, The University of Western Australia, Perth, WA, Australia
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Siddiqui R, Badran Z, Boghossian A, Alharbi AM, Alfahemi H, Khan NA. The increasing importance of the oral microbiome in periodontal health and disease. Future Sci OA 2023; 9:FSO856. [PMID: 37621848 PMCID: PMC10445586 DOI: 10.2144/fsoa-2023-0062] [Citation(s) in RCA: 25] [Impact Index Per Article: 12.5] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/19/2023] [Accepted: 05/30/2023] [Indexed: 08/26/2023] Open
Abstract
Herein, the aim is to discuss the current knowledge of microbiome and periodontal diseases. Current treatment strategies include mechanical therapy such as root planing, scaling, deep pocket debridement and antimicrobial chemotherapy as an adjuvant therapy. Among promising therapeutic strategies, dental probiotics and oral microbiome transplantation have gained attention, and may be used to treat bacterial imbalances by competing with pathogenic bacteria for nutrients and adhesion surfaces, as well as probiotics targeting the gut microbiome. Development of strategies to prevent and treat periodontal diseases are warranted as both are highly prevalent and can affect human health. Further studies are necessary to better comprehend the microbiome in order to develop innovative preventative measures as well as efficacious therapies against periodontal diseases.
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Affiliation(s)
- Ruqaiyyah Siddiqui
- College of Arts & Sciences, American University of Sharjah, Sharjah, 26666, United Arab Emirates
- Department of Medical Biology, Faculty of Medicine, Istinye University, Istanbul, 34010, Turkey
| | - Zahi Badran
- Periodontology Unit, Department of Preventive & Restorative Dentistry, College of Dental Medicine, University of Sharjah, Sharjah, 27272, United Arab Emirates
| | - Anania Boghossian
- College of Arts & Sciences, American University of Sharjah, Sharjah, 26666, United Arab Emirates
| | - Ahmad M Alharbi
- Department of Clinical Laboratory Sciences, College of Applied Medical Sciences, Taif University, Taif, 21944, Saudi Arabia
| | - Hasan Alfahemi
- Department of Medical Microbiology, Faculty of Medicine, Al-Baha University, Al-Baha, 65799, Saudi Arabia
| | - Naveed Ahmed Khan
- Department of Medical Biology, Faculty of Medicine, Istinye University, Istanbul, 34010, Turkey
- Department of Clinical Sciences, College of Medicine, University of Sharjah, University City, Sharjah, United Arab Emirates
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21
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Zhao M, Xie Y, Gao W, Li C, Ye Q, Li Y. Diabetes mellitus promotes susceptibility to periodontitis-novel insight into the molecular mechanisms. Front Endocrinol (Lausanne) 2023; 14:1192625. [PMID: 37664859 PMCID: PMC10469003 DOI: 10.3389/fendo.2023.1192625] [Citation(s) in RCA: 33] [Impact Index Per Article: 16.5] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 03/23/2023] [Accepted: 07/24/2023] [Indexed: 09/05/2023] Open
Abstract
Diabetes mellitus is a main risk factor for periodontitis, but until now, the underlying molecular mechanisms remain unclear. Diabetes can increase the pathogenicity of the periodontal microbiota and the inflammatory/host immune response of the periodontium. Hyperglycemia induces reactive oxygen species (ROS) production and enhances oxidative stress (OS), exacerbating periodontal tissue destruction. Furthermore, the alveolar bone resorption damage and the epigenetic changes in periodontal tissue induced by diabetes may also contribute to periodontitis. We will review the latest clinical data on the evidence of diabetes promoting the susceptibility of periodontitis from epidemiological, molecular mechanistic, and potential therapeutic targets and discuss the possible molecular mechanistic targets, focusing in particular on novel data on inflammatory/host immune response and OS. Understanding the intertwined pathogenesis of diabetes mellitus and periodontitis can explain the cross-interference between endocrine metabolic and inflammatory diseases better, provide a theoretical basis for new systemic holistic treatment, and promote interprofessional collaboration between endocrine physicians and dentists.
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Affiliation(s)
- Mingcan Zhao
- Department of Pediatric Dentistry, Hospital of Stomatology, Jilin University, Changchun, Jilin, China
| | - Yuandong Xie
- Department of Pediatric Dentistry, Hospital of Stomatology, Jilin University, Changchun, Jilin, China
- Jilin Provincial Key Laboratory of Tooth Development and Bone Remodeling, Hospital of Stomatology, Jilin University, Changchun, Jilin, China
| | - Wenjia Gao
- Department of Pediatric Dentistry, Hospital of Stomatology, Jilin University, Changchun, Jilin, China
- Jilin Provincial Key Laboratory of Tooth Development and Bone Remodeling, Hospital of Stomatology, Jilin University, Changchun, Jilin, China
| | - Chunwang Li
- Department of Pediatric Dentistry, Hospital of Stomatology, Jilin University, Changchun, Jilin, China
- Jilin Provincial Key Laboratory of Tooth Development and Bone Remodeling, Hospital of Stomatology, Jilin University, Changchun, Jilin, China
| | - Qiang Ye
- Department of Pediatric Dentistry, Hospital of Stomatology, Jilin University, Changchun, Jilin, China
| | - Yi Li
- Department of Pediatric Dentistry, Hospital of Stomatology, Jilin University, Changchun, Jilin, China
- Jilin Provincial Key Laboratory of Tooth Development and Bone Remodeling, Hospital of Stomatology, Jilin University, Changchun, Jilin, China
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Irie K, Azuma T, Tomofuji T, Yamamoto T. Exploring the Role of IL-17A in Oral Dysbiosis-Associated Periodontitis and Its Correlation with Systemic Inflammatory Disease. Dent J (Basel) 2023; 11:194. [PMID: 37623290 PMCID: PMC10453731 DOI: 10.3390/dj11080194] [Citation(s) in RCA: 10] [Impact Index Per Article: 5.0] [Reference Citation Analysis] [Abstract] [Key Words] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/16/2023] [Revised: 08/01/2023] [Accepted: 08/09/2023] [Indexed: 08/26/2023] Open
Abstract
Oral microbiota play a pivotal role in maintaining homeostasis, safeguarding the oral cavity, and preventing the onset of disease. Oral dysbiosis has the potential to trigger pro-inflammatory effects and immune dysregulation, which can have a negative impact on systemic health. It is regarded as a key etiological factor for periodontitis. The emergence and persistence of oral dysbiosis have been demonstrated to mediate inflammatory pathology locally and at distant sites. The heightened inflammation observed in oral dysbiosis is dependent upon the secretion of interleukin-17A (IL-17A) by various innate and adaptive immune cells. IL-17A has been found to play a significant role in host defense mechanisms by inducing antibacterial peptides, recruiting neutrophils, and promoting local inflammation via cytokines and chemokines. This review seeks to present the current knowledge on oral dysbiosis and its prevention, as well as the underlying role of IL-17A in periodontitis induced by oral dysbiosis and its impact on systemic inflammatory disease.
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Affiliation(s)
- Koichiro Irie
- Department of Preventive Dentistry and Dental Public Health, Kanagawa Dental University, Yokosuka 238-8580, Japan;
| | - Tetsuji Azuma
- Department of Community Oral Health, School of Dentistry, Asahi University, Mizuho 501-0296, Japan; (T.A.); (T.T.)
| | - Takaaki Tomofuji
- Department of Community Oral Health, School of Dentistry, Asahi University, Mizuho 501-0296, Japan; (T.A.); (T.T.)
| | - Tatsuo Yamamoto
- Department of Preventive Dentistry and Dental Public Health, Kanagawa Dental University, Yokosuka 238-8580, Japan;
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23
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Liu J, Zhou L, Sun L, Ye X, Ma M, Dou M, Shi L. Association Between Intestinal Prevotella copri Abundance and Glycemic Fluctuation in Patients with Brittle Diabetes. Diabetes Metab Syndr Obes 2023; 16:1613-1621. [PMID: 37292141 PMCID: PMC10246570 DOI: 10.2147/dmso.s412872] [Citation(s) in RCA: 5] [Impact Index Per Article: 2.5] [Reference Citation Analysis] [Abstract] [Key Words] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 03/16/2023] [Accepted: 05/13/2023] [Indexed: 06/10/2023] Open
Abstract
Objective Previous studies have demonstrated an association between gut microbiota composition and non-brittle type 2 diabetes (NBT2DM) pathogenesis. However, little is known about the correlation between the abundance of intestinal Prevotella copri and glycemic fluctuations in patients with brittle diabetes mellitus (BDM). In this context, we conducted a case-control study of BDM patients and patients with NBT2DM, aiming to determine and analyze the relationship between the abundance of intestinal Prevotella copri and glycemic fluctuations in patients with BDM. Research Design and methods We performed a metagenomic analysis of the gut microbiome obtained from fecal samples of 10 BDM patients, and compared their microbial composition and function to NBT2DM patients (1:1 ratio). Then further collected data including age, sex, BMI, glycated hemoglobin (HbA1c), blood lipids, and alpha diversity of the gut microbiota, which were comparable between the BDM and NBT2DM patients by t-test. Results A significant difference existed in the beta diversity of the gut microbiota between the two groups (PCoA, R2 = 0.254, P = 0.0001). The phylum-level abundance of Bacteroidetes in the gut microbiota of the BDM patients was significantly lower, by 24.9% (P = 0.001), than that of the NBT2DM patients. At the gene level, the abundance of Prevotella copri was obviously reduced, Correlation analysis showed that the Prevotella copri abundance was inversely correlated to the standard deviation of blood glucose (SDBG) (r = -0.477, P = 0.034). Quantitative PCR confirmed that the abundance of Prevotella copri in the BDM patients in the validation cohort was significantly lower than that in NBT2DM patients, and was negatively correlated with SDBG (r = -0.318, P = 0.043). Glycemic variability in BDM was inversely correlated with the abundance of intestinal Prevotella copri. Conclusion The decreased abundance of Prevotella copri in patients with BDM may be associated with glycemic fluctuation.
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Affiliation(s)
- Juan Liu
- Department of Endocrinology, The Affiliated Changzhou No.2 People’s Hospital of Nanjing Medical University, Changzhou, Jiangsu, 213164, People’s Republic of China
| | - Liang Zhou
- Department of Endocrinology, The Affiliated Changzhou No.2 People’s Hospital of Nanjing Medical University, Changzhou, Jiangsu, 213164, People’s Republic of China
| | - Lili Sun
- Department of Endocrinology, The Affiliated Changzhou No.2 People’s Hospital of Nanjing Medical University, Changzhou, Jiangsu, 213164, People’s Republic of China
| | - Xinhua Ye
- Department of Endocrinology, The Affiliated Changzhou No.2 People’s Hospital of Nanjing Medical University, Changzhou, Jiangsu, 213164, People’s Republic of China
| | - Menglu Ma
- Bengbu Medical College, Bengbu, Anhui, 233000, People’s Republic of China
| | - Min Dou
- Bengbu Medical College, Bengbu, Anhui, 233000, People’s Republic of China
| | - Li Shi
- Department of Endocrinology, The Affiliated Changzhou No.2 People’s Hospital of Nanjing Medical University, Changzhou, Jiangsu, 213164, People’s Republic of China
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Lim MY, Kim JH, Nam YD. Oral microbiome correlates with selected clinical biomarkers in individuals with no significant systemic disease. Front Cell Infect Microbiol 2023; 13:1114014. [PMID: 37065205 PMCID: PMC10102430 DOI: 10.3389/fcimb.2023.1114014] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/02/2022] [Accepted: 03/20/2023] [Indexed: 04/03/2023] Open
Abstract
The oral microbiome is an important component of the microbiome in the human body. Although the association of the oral microbiome with various diseases, including periodontitis and cancer, has been reported, information on how the oral microbiome is related to health-related indicators in healthy populations is still insufficient. In this study, we examined the associations of the oral microbiome with 15 metabolic and 19 complete blood count (CBC)-based markers in 692 healthy Korean individuals. The richness of the oral microbiome was associated with four CBC markers and one metabolic marker. Compositional variation in the oral microbiome was significantly explained by four markers: fasting glucose, fasting insulin, white blood cell count, and total leukocyte count. Furthermore, we found that these biomarkers were associated with the relative abundances of numerous microbial genera, such as Treponema, TG5, and Tannerella. By identifying the relationship between the oral microbiome and clinical biomarkers in a healthy population, our study presents a direction for future studies on oral microbiome-based diagnosis and interventions.
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Affiliation(s)
- Mi Young Lim
- Personalized Diet Research Group, Korea Food Research Institute, Jeollabuk-do, Republic of Korea
| | - Jung-Ha Kim
- Department of Family Medicine, Chung-Ang University Hospital, Chung-Ang University College of Medicine, Seoul, Republic of Korea
| | - Young-Do Nam
- Personalized Diet Research Group, Korea Food Research Institute, Jeollabuk-do, Republic of Korea
- *Correspondence: Young-Do Nam,
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Guo XJ, Dai SX, Lou JD, Ma XX, Hu XJ, Tu LP, Cui J, Lu H, Jiang T, Xu JT. Distribution characteristics of oral microbiota and its relationship with intestinal microbiota in patients with type 2 diabetes mellitus. Front Endocrinol (Lausanne) 2023; 14:1119201. [PMID: 37025407 PMCID: PMC10072265 DOI: 10.3389/fendo.2023.1119201] [Citation(s) in RCA: 17] [Impact Index Per Article: 8.5] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 12/08/2022] [Accepted: 02/23/2023] [Indexed: 03/18/2023] Open
Abstract
Introduction Type 2 diabetes mellitus (T2DM) has a high incidence rate globally, increasing the burden of death, disability, and the economy worldwide. Previous studies have found that the compositions of oral and intestinal microbiota changed respectively in T2DM; whether the changes were associated or interacted between the two sites and whether there were some associations between T2DM and the ectopic colonization of oral microbiota in the gut still need to be identified. Research design and methods We performed a cross-sectional observational study; 183 diabetes and 74 controls were enrolled. We used high-throughput sequencing technology to detect the V3-V4 region of 16S rRNA in oral and stool samples. The Source Tracker method was used to identify the proportion of the intestinal microbiota that ectopic colonized from the oral cavity. Results The oral marker bacteria of T2DM were found, such as Actinobacteria, Streptococcus, Rothia, and the intestinal marker bacteria were Bifidobacterium, Streptococcus, and Blautia at the genus level. Among them, Actinobacteria and Blautia played a vital role in different symbiotic relationships of oral and intestinal microbiota. The commonly distributed bacteria, such as Firmicutes, Bacteroidetes, and Actinobacteria, were found in both oral and intestine. Moreover, the relative abundance and composition of bacteria were different between the two sites. The glycine betaine degradation I pathway was the significantly up-regulated pathway in the oral and intestinal flora of T2DM. The main serum indexes related to oral and intestinal flora were inflammatory. The relative abundance of Proteobacteria in the intestine and the Spirochete in oral was positively correlated, and the correlation coefficient was the highest, was 0.240 (P<0.01). The proportion of ectopic colonization of oral flora in the gut of T2DM was 2.36%. Conclusion The dysbacteriosis exited in the oral and intestine simultaneously, and there were differences and connections in the flora composition at the two sites in T2DM. Ectopic colonization of oral flora in the intestine might relate to T2DM. Further, clarifying the oral-gut-transmitting bacteria can provide an essential reference for diagnosing and treating T2DM in the future.
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Affiliation(s)
- Xiao-jing Guo
- School of Basic Medical Sciences, Shanghai University of Traditional Chinese Medicine, Shanghai, China
- School of Anesthesiology, Naval Medical University, Shanghai, China
| | - Shi-xuan Dai
- School of Basic Medical Sciences, Shanghai University of Traditional Chinese Medicine, Shanghai, China
| | - Jin-di Lou
- School of Basic Medical Sciences, Shanghai University of Traditional Chinese Medicine, Shanghai, China
| | - Xu-xiang Ma
- School of Basic Medical Sciences, Shanghai University of Traditional Chinese Medicine, Shanghai, China
| | - Xiao-juan Hu
- Shanghai Collaborative Innovation Center of Health Service in Traditional Chinese Medicine, Shanghai University of Traditional Chinese Medicine, Shanghai, China
| | - Li-ping Tu
- School of Basic Medical Sciences, Shanghai University of Traditional Chinese Medicine, Shanghai, China
| | - Ji Cui
- School of Basic Medical Sciences, Shanghai University of Traditional Chinese Medicine, Shanghai, China
| | - Hao Lu
- Department of Endocrinology, Shuguang Hospital Affiliated to Shanghai University of Traditional Chinese Medicine, Shanghai, China
| | - Tao Jiang
- School of Basic Medical Sciences, Shanghai University of Traditional Chinese Medicine, Shanghai, China
| | - Jia-tuo Xu
- School of Basic Medical Sciences, Shanghai University of Traditional Chinese Medicine, Shanghai, China
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Keni R, Begum F, Gourishetti K, Viswanatha GL, Nayak PG, Nandakumar K, Shenoy RR. Diabetic wound healing approaches: an update. J Basic Clin Physiol Pharmacol 2023; 34:137-150. [PMID: 34995024 DOI: 10.1515/jbcpp-2021-0340] [Citation(s) in RCA: 15] [Impact Index Per Article: 7.5] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/09/2021] [Accepted: 12/19/2021] [Indexed: 01/01/2023]
Abstract
Diabetic wounds are of profound clinical importance. Despite immense efforts directed towards its management, it results in the development of amputations, following a diagnosis of diabetic foot. With a better understanding of the complexities of the microbalance involved in the healing process, researchers have developed advanced methods for the management of wounds as well as diagnostic tools (especially, for wound infections) to be delivered to clinics sooner. In this review, we address the newer developments that hope to drive the transition from bench to bedside in the coming decade.
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Affiliation(s)
- Raghuvir Keni
- Department of Pharmacology, Manipal College of Pharmaceutical Sciences, Manipal Academy of Higher Education, Manipal, Karnataka, India
| | - Farmiza Begum
- Department of Pharmacology, Manipal College of Pharmaceutical Sciences, Manipal Academy of Higher Education, Manipal, Karnataka, India
| | - Karthik Gourishetti
- Department of Pharmacology, Manipal College of Pharmaceutical Sciences, Manipal Academy of Higher Education, Manipal, Karnataka, India
| | | | - Pawan Ganesh Nayak
- Department of Pharmacology, Manipal College of Pharmaceutical Sciences, Manipal Academy of Higher Education, Manipal, Karnataka, India
| | - Krishnadas Nandakumar
- Department of Pharmacology, Manipal College of Pharmaceutical Sciences, Manipal Academy of Higher Education, Manipal, Karnataka, India
| | - Rekha R Shenoy
- Department of Pharmacology, Manipal College of Pharmaceutical Sciences, Manipal Academy of Higher Education, Manipal, Karnataka, India
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Li Y, Qian F, Cheng X, Wang D, Wang Y, Pan Y, Chen L, Wang W, Tian Y. Dysbiosis of Oral Microbiota and Metabolite Profiles Associated with Type 2 Diabetes Mellitus. Microbiol Spectr 2023; 11:e0379622. [PMID: 36625596 PMCID: PMC9927158 DOI: 10.1128/spectrum.03796-22] [Citation(s) in RCA: 19] [Impact Index Per Article: 9.5] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/19/2022] [Accepted: 12/12/2022] [Indexed: 01/11/2023] Open
Abstract
Several previous studies have shown that oral microbial disorders may be closely related to the occurrence and development of type 2 diabetes mellitus (T2DM). However, whether the function of oral microorganisms and their metabolites have changed in patients with T2DM who have not suffered from any oral diseases has not been reported. We performed metagenomic analyses and nontargeted metabolic analysis of saliva and supragingival plaque samples from patients with T2DM who have not suffered any oral diseases and normal controls. We found that periodontal pathogens such as Porphyromonas gingivalis and Prevotella melaninogenica were significantly enriched, while the abundances of dental caries pathogens such as Streptococcus mutans and Streptococcus sobrinus were not significantly different in patients with T2DM compared to those in normal controls. Metabolomic analyses showed that the salivary levels of cadaverine and L-(+)-leucine of patients with T2DM were significantly higher than those of normal controls, while the supragingival plaque levels of N-acetyldopamine and 3,4-dimethylbenzoic acid in patients with T2DM were significantly higher than those in the normal controls. Additionally, we identified the types of oral microorganisms related to the changes in the levels of circulating metabolites, and the oral microorganisms were involved in the dysregulation of harmful metabolites such as cadaverine and n, n-dimethylarginine. Overall, our study first described the changes in the composition of oral microorganisms and their metabolites in patients with T2DM who have not suffered any oral diseases, which will provide a direct basis for finding oral biomarkers for early warning of oral diseases in T2DM. IMPORTANCE The incidence of oral diseases in type 2 diabetic patients might increase, and the severity might also be more serious. At present, the relationship between oral microorganisms and type 2 diabetes mellitus (T2DM) has become a hot topic in systemic health research. However, whether the function of oral microorganisms and their metabolites have changed in patients with T2DM who have not suffered from any oral diseases has not been reported. We found that even if the oral condition of T2DM is healthy, their oral microbes and metabolites have changed, thus increasing the risk of periodontal disease. Our study first described the changes in the composition of oral microorganisms and their metabolites in T2DM who have not suffered any oral diseases and revealed the correlation between oral microorganisms and their metabolites, which will provide a direct basis for finding oral biomarkers for early warning of oral diseases in patients with T2DM.
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Affiliation(s)
- Yujiao Li
- State Key Laboratory of Military Stomatology & National Clinical Research Center for Oral Diseases & Shaanxi Key Laboratory of Stomatology & Department of Operative Dentistry and Endodontics, School of Stomatology, the Fourth Military Medical University, Xi’an, People’s Republic of China
| | - Fei Qian
- State Key Laboratory of Military Stomatology & National Clinical Research Center for Oral Diseases & Shaanxi Key Laboratory of Stomatology & Department of Prosthodontics, School of Stomatology, the Fourth Military Medical University, Xi’an, People’s Republic of China
| | - Xiaogang Cheng
- State Key Laboratory of Military Stomatology & National Clinical Research Center for Oral Diseases & Shaanxi Key Laboratory of Stomatology & Department of Operative Dentistry and Endodontics, School of Stomatology, the Fourth Military Medical University, Xi’an, People’s Republic of China
| | - Dan Wang
- State Key Laboratory of Military Stomatology & National Clinical Research Center for Oral Diseases & Shaanxi Key Laboratory of Stomatology & Department of Operative Dentistry and Endodontics, School of Stomatology, the Fourth Military Medical University, Xi’an, People’s Republic of China
| | - Yirong Wang
- State Key Laboratory of Military Stomatology & National Clinical Research Center for Oral Diseases & Shaanxi Key Laboratory of Stomatology & Department of Operative Dentistry and Endodontics, School of Stomatology, the Fourth Military Medical University, Xi’an, People’s Republic of China
| | - Yating Pan
- State Key Laboratory of Military Stomatology & National Clinical Research Center for Oral Diseases & Shaanxi Key Laboratory of Stomatology & Department of Operative Dentistry and Endodontics, School of Stomatology, the Fourth Military Medical University, Xi’an, People’s Republic of China
| | - Liyuan Chen
- State Key Laboratory of Military Stomatology & National Clinical Research Center for Oral Diseases & Shaanxi Key Laboratory of Stomatology & Department of Operative Dentistry and Endodontics, School of Stomatology, the Fourth Military Medical University, Xi’an, People’s Republic of China
| | - Wei Wang
- State Key Laboratory of Military Stomatology & National Clinical Research Center for Oral Diseases & Shaanxi Key Laboratory of Stomatology & Department of Operative Dentistry and Endodontics, School of Stomatology, the Fourth Military Medical University, Xi’an, People’s Republic of China
| | - Yu Tian
- State Key Laboratory of Military Stomatology & National Clinical Research Center for Oral Diseases & Shaanxi Key Laboratory of Stomatology & Department of Operative Dentistry and Endodontics, School of Stomatology, the Fourth Military Medical University, Xi’an, People’s Republic of China
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Hardinsyah H, Nurkolis F, Kurniawan R, Gunawan WB, Augusta PS, Setyawardani A, Agustianto RF, Al Mahira MFN, Praditya GN, Lailossa DG, Yudisthira D, Farradisya S, Barazani H. Can salivary microbiome become a biodetector for type-2 diabetes? Opinion for future implications and strategies. Front Nutr 2023; 10:1113591. [PMID: 36742425 PMCID: PMC9892936 DOI: 10.3389/fnut.2023.1113591] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Key Words] [Track Full Text] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/01/2022] [Accepted: 01/05/2023] [Indexed: 01/20/2023] Open
Affiliation(s)
- Hardinsyah Hardinsyah
- Division of Applied Nutrition, Faculty of Human Ecology, Department of Community Nutrition, IPB University, Bogor, Indonesia,*Correspondence: Hardinsyah Hardinsyah,
| | - Fahrul Nurkolis
- Department of Biological Sciences, Faculty of Sciences and Technology, State Islamic University of Sunan Kalijaga (UIN Sunan Kalijaga Yogyakarta), Yogyakarta, Indonesia
| | - Rudy Kurniawan
- Alumnus of Department of Internal Medicine, Faculty of Medicine, University of Indonesia–Cipto Mangunkusumo Hospital, Jakarta, Indonesia
| | - William Ben Gunawan
- Alumnus of Department of Nutrition Science, Faculty of Medicine, Diponegoro University, Semarang, Indonesia
| | - Piko Satria Augusta
- Medical Study Programme, Faculty of Medicine, Brawijaya University, Malang, Indonesia
| | - Astuti Setyawardani
- Medical Student of Faculty of Medicine, University of Jember–Soebandi Regional Hospital, Jember, Indonesia
| | | | | | | | | | - Dewangga Yudisthira
- Medical Study Programme, Faculty of Medicine, Brawijaya University, Malang, Indonesia
| | - Salsabila Farradisya
- Medical Study Programme, Faculty of Medicine, Brawijaya University, Malang, Indonesia
| | - Hero Barazani
- Medical Study Programme, Faculty of Medicine, Brawijaya University, Malang, Indonesia
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Zhao H, Zong Y, Li W, Wang Y, Zhao W, Meng X, Yang F, Kong J, Zhao X, Wang J. Damp-heat constitution influences gut microbiota and urine metabolism of Chinese infants. Heliyon 2022; 9:e12424. [PMID: 36755610 PMCID: PMC9900481 DOI: 10.1016/j.heliyon.2022.e12424] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/28/2022] [Revised: 11/15/2022] [Accepted: 12/09/2022] [Indexed: 12/25/2022] Open
Abstract
Background As an increasingly popular complementary and alternative approach for early detection and treatment of disease, traditional Chinese medicine constitution (TCMC) divides human beings into those with balanced constitution (BC) and unbalanced constitution, where damp-heat constitution (DHC) is one of the most unbalanced constitutions. Many studies have been carried out on the microscopic mechanism of constitution classification; however, most of these studies were conducted in adults and rarely in infants. Many diseases are closely related to intestinal microbiota, and metabolites produced by the interaction between microbiota and the body may impact constitution classification. Herein, we investigated the overall constitution distribution in Chinese infants, and analyzed the profiles of gut microbiota and urine metabolites of DHC to further promote the understanding of infants constitution classification. Methods General information was collected and TCMC was evaluated by Constitutional Medicine Questionnaires. 1315 questionnaires were received in a cross-sectional study to investigate the constitution composition in Chinese infants. A total of 56 infants, including 30 DHC and 26 BC, were randomly selected to analyze gut microbiota by 16S rRNA sequencing and urine metabolites by UPLC-Q-TOF/MS method. Results BC was the most common constitution in Chinese infants, DHC was the second common constitution. The gut microbiota and urine metabolites in the DHC group showed different composition compared to the BC group. Four differential genera and twenty differential metabolites were identified. In addition, the combined marker composed of four metabolites may have the high potential to discriminate DHC from BC with an AUC of 0.765. Conclusions The study revealed the systematic differences in the gut microbiota and urine metabolites between infants with DHC and BC. Moreover, the differential microbiota and metabolites may offer objective evidences for constitution classification.
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Affiliation(s)
- Haihong Zhao
- National Institute of Traditional Chinese Medicine Constitution and Preventive Treatment of Disease, Beijing University of Chinese Medicine, Beijing, 100029, China
| | - Yuhan Zong
- National Institute of Traditional Chinese Medicine Constitution and Preventive Treatment of Disease, Beijing University of Chinese Medicine, Beijing, 100029, China
| | - Wenle Li
- National Institute of Traditional Chinese Medicine Constitution and Preventive Treatment of Disease, Beijing University of Chinese Medicine, Beijing, 100029, China
| | - Yaqi Wang
- College of Basic Medical Sciences, Zhejiang Chinese Medical University, Hangzhou, 310053, Zhejiang, China
| | - Weibo Zhao
- National Institute of Traditional Chinese Medicine Constitution and Preventive Treatment of Disease, Beijing University of Chinese Medicine, Beijing, 100029, China
| | - Xianghe Meng
- Neurology Department, Xuanwu Hospital of Capital Medical University, Beijing, 100053, China
| | - Fan Yang
- National Institute of Traditional Chinese Medicine Constitution and Preventive Treatment of Disease, Beijing University of Chinese Medicine, Beijing, 100029, China
| | - Jingwei Kong
- Nutrition and Metabolism Research Division, Innovation Center, Heilongjiang Feihe Dairy Co., Ltd., Beijing, 100015, China
| | - Xiaoshan Zhao
- National Institute of Traditional Chinese Medicine Constitution and Preventive Treatment of Disease, Beijing University of Chinese Medicine, Beijing, 100029, China,School of Chinese Medicine, Southern Medical University, Guangzhou, 510515, Guangdong, China
| | - Ji Wang
- National Institute of Traditional Chinese Medicine Constitution and Preventive Treatment of Disease, Beijing University of Chinese Medicine, Beijing, 100029, China,Corresponding author.
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Poulsen CS, Nygaard N, Constancias F, Stankevic E, Kern T, Witte DR, Vistisen D, Grarup N, Pedersen OB, Belstrøm D, Hansen T. Association of general health and lifestyle factors with the salivary microbiota - Lessons learned from the ADDITION-PRO cohort. Front Cell Infect Microbiol 2022; 12:1055117. [PMID: 36467723 PMCID: PMC9709502 DOI: 10.3389/fcimb.2022.1055117] [Citation(s) in RCA: 4] [Impact Index Per Article: 1.3] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/27/2022] [Accepted: 10/24/2022] [Indexed: 07/20/2023] Open
Abstract
INTRODUCTION Previous research indicates that the salivary microbiota may be a biomarker of oral as well as systemic disease. However, clarifying the potential bias from general health status and lifestyle-associated factors is a prerequisite of using the salivary microbiota for screening. MATERIALS & METHODS ADDDITION-PRO is a nationwide Danish cohort, nested within the Danish arm of the Anglo-Danish-Dutch Study of Intensive treatment in People with Screen-Detected Diabetes in Primary Care. Saliva samples from n=746 individuals from the ADDITION-PRO cohort were characterized using 16s rRNA sequencing. Alpha- and beta diversity as well as relative abundance of genera was examined in relation to general health and lifestyle-associated variables. Permutational multivariate analysis of variance (PERMANOVA) was performed on individual variables and all variables together. Classification models were created using sparse partial-least squares discriminant analysis (sPLSDA) for variables that showed statistically significant differences based on PERMANOVA analysis (p < 0.05). RESULTS Glycemic status, hemoglobin-A1c (HbA1c) level, sex, smoking and weekly alcohol intake were found to be significantly associated with salivary microbial composition (individual variables PERMANOVA, p < 0.05). Collectively, these variables were associated with approximately 5.8% of the observed differences in the composition of the salivary microbiota. Smoking status was associated with 3.3% of observed difference, and smoking could be detected with good accuracy based on salivary microbial composition (AUC 0.95, correct classification rate 79.6%). CONCLUSIONS Glycemic status, HbA1c level, sex, smoking and weekly alcohol intake were significantly associated with the composition of the salivary microbiota. Despite smoking only being associated with 3.3% of the difference in overall salivary microbial composition, it was possible to create a model for detection of smoking status with a high correct classification rate. However, the lack of information on the oral health status of participants serves as a limitation in the present study. Further studies in other cohorts are needed to validate the external validity of these findings.
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Affiliation(s)
- Casper Sahl Poulsen
- The Novo Nordisk Foundation Center for Basic Metabolic Research, Faculty of Health and Medical Sciences, Copenhagen University, Copenhagen, Denmark
| | - Nikoline Nygaard
- The Novo Nordisk Foundation Center for Basic Metabolic Research, Faculty of Health and Medical Sciences, Copenhagen University, Copenhagen, Denmark
- Institute of Odontology, Section of Oral Microbiology, Faculty of Health and Medical Sciences, Copenhagen University, Copenhagen, Denmark
| | - Florentin Constancias
- Swiss Federal Institute of Technology in Zürich, Department of Health Sciences and Technology, Zürich, Switzerland
| | - Evelina Stankevic
- The Novo Nordisk Foundation Center for Basic Metabolic Research, Faculty of Health and Medical Sciences, Copenhagen University, Copenhagen, Denmark
| | - Timo Kern
- The Novo Nordisk Foundation Center for Basic Metabolic Research, Faculty of Health and Medical Sciences, Copenhagen University, Copenhagen, Denmark
| | - Daniel R. Witte
- Department of Public Health, Aarhus University, Aarhus, Denmark
- Steno Diabetes Center Aarhus, Aarhus, Denmark
| | - Dorte Vistisen
- Steno Diabetes Center, Copenhagen, Denmark
- Department of Public Health, University of Copenhagen, Copenhagen, Denmark
| | - Niels Grarup
- The Novo Nordisk Foundation Center for Basic Metabolic Research, Faculty of Health and Medical Sciences, Copenhagen University, Copenhagen, Denmark
| | - Oluf Borbye Pedersen
- The Novo Nordisk Foundation Center for Basic Metabolic Research, Faculty of Health and Medical Sciences, Copenhagen University, Copenhagen, Denmark
- Center for Clinical Metabolic Research, Herlev-Gentofte Hospital, Gentofte, Denmark
| | - Daniel Belstrøm
- Institute of Odontology, Section of Oral Microbiology, Faculty of Health and Medical Sciences, Copenhagen University, Copenhagen, Denmark
| | - Torben Hansen
- The Novo Nordisk Foundation Center for Basic Metabolic Research, Faculty of Health and Medical Sciences, Copenhagen University, Copenhagen, Denmark
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Feng Y, Wu C, Huang X, Huang X, Peng L, Guo R. Case report: Successful management of Parvimonas micra pneumonia mimicking hematogenous Staphylococcus aureus pneumonia. Front Med (Lausanne) 2022; 9:1017074. [PMID: 36388879 PMCID: PMC9651478 DOI: 10.3389/fmed.2022.1017074] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/11/2022] [Accepted: 09/30/2022] [Indexed: 05/18/2025] Open
Abstract
Parvimonas micra is an anaerobic Gram-positive coccus frequently found in the oral cavity and gastrointestinal tract, but rarely in the lung. Therefore, pneumonia caused by P. micra is also rare. Although there are some reports of P. micra related pneumonia due to aspiration or blood-borne infection with definite remote infection source, there are no reported cases of hematogenous P. micra pneumonia in healthy adults lacking a remote source of infection. Herein, we described the intact disease of P. micra-related pneumonia mimicking hematogenous Staphylococcus aureus pneumonia in terms of chest imagery and diagnosed via metagenomic next-generation sequencing (mNGS). Interestingly, there was no clear remote pathogenic source identified in the patient. Microbiome analysis revealed dysbiosis of the oral flora possibly related to poor oral hygiene and a long history of smoking. The patient was treated with moxifloxacin for 3 months. Ultimately, computed tomography (CT) of the chest showed total resolution of the lung lesion. Clinicians need to update the etiology of community-acquired pneumonia. When antibiotic therapy is not effective, pathogen examination becomes very important. New methods of pathogen detection such as mNGS should be employed to this end. For the treatment of P. micra pneumonia, no standardized course of treatment was reported. Imaging absorption of lung infections may provide a more objective guidance for the duration of antibiotics in P. micra pneumonia.
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Affiliation(s)
- Yanmei Feng
- Department of Respiratory and Critical Care Medicine, The First Affiliated Hospital of Chongqing Medical University, Chongqing, China
| | - Chunxia Wu
- Department of Respiratory and Critical Care Medicine, The First Affiliated Hospital of Chongqing Medical University, Chongqing, China
| | - Xiaohui Huang
- Department of Respiratory and Critical Care Medicine, Liangping People’s Hospital, Chongqing, China
| | - Xia Huang
- Department of Critical Care Medicine, Chongqing University Three Gorges Hospital, Chongqing, China
| | - Li Peng
- Department of Respiratory and Critical Care Medicine, The First Affiliated Hospital of Chongqing Medical University, Chongqing, China
| | - Rui Guo
- Department of Critical Care Medicine, The First Affiliated Hospital of Chongqing Medical University, Chongqing, China
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Lu C, Zhao Q, Deng J, Chen K, Jiang X, Ma F, Ma S, Li Z. Salivary Microbiome Profile of Diabetes and Periodontitis in a Chinese Population. Front Cell Infect Microbiol 2022; 12:933833. [PMID: 35979090 PMCID: PMC9377223 DOI: 10.3389/fcimb.2022.933833] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [MESH Headings] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/01/2022] [Accepted: 06/06/2022] [Indexed: 11/15/2022] Open
Abstract
Aim There is a bidirectional association between diabetes and periodontitis. However, the effect of diabetes on the periodontitis salivary microbiota has not been elucidated. The aim of this study was to determine the effect of the presence of diabetes on the microbiota among Chinese patients with periodontitis. Materials and Methods Unstimulated whole saliva samples were collected from the periodontitis with diabetes group (TC), chronic periodontitis group (CP), and periodontally healthy and systemically healthy group (H) by spitting method. Bacterial genomic DNA was PCR-amplified at the V4 variable region of 16S rRNA gene. The library was constructed according to the obtained sequence results, and biological analysis and statistical analysis were carried out. Functional prediction of three groups of microbial communities was performed by the PICRUSt algorithm. Results There was no significant difference in bacterial diversity between the TC and CP groups. Compared with the H group, the TC group and CP group presented a higher diversity of salivary flora. Firmicutes, Streptococcus, Haemophilus, Veillonella, and Haemophilus parainfluenzae dominated the H group. Corynebacterium, Leptotrichia, Dialister, Comamonas, Capnocytophaga, Catonella, Filifactor, Campylobacter, Treponema, Campylobacter concisus, Prevotella oralis, and Porphyromonas gingivalis were significantly enriched in the TC and CP groups. Among them, Treponema and P. oralis were the most abundant in the TC group. The PICRUSt results showed that many pathways related to cell motility and functional metabolism of the salivary microbial flora changed in the TC group and the CP group. Conclusions Diabetes was not the main factor causing the altered diversity of salivary microbiota in patients with periodontitis; however, the presence of diabetes altered the abundance of some microbiota in saliva.
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Affiliation(s)
- Chunting Lu
- Science and Education Office, The First Affiliated Hospital, Jinan University, Guangzhou, China
| | - Qingtong Zhao
- Department of Stomatology, The Sixth Affiliated Hospital of Jinan University, Dongguan, China
| | - Jianwen Deng
- School of Stomatology, Jinan University, Guangzhou, China
| | - Kexiao Chen
- School of Stomatology, Jinan University, Guangzhou, China
| | - Xinrong Jiang
- School of Stomatology, Jinan University, Guangzhou, China
| | - Fengyu Ma
- School of Stomatology, Jinan University, Guangzhou, China
| | - Shuyuan Ma
- Medical Center of Stomatology, The First Affiliated Hospital, Jinan University, Guangzhou, China
| | - Zejian Li
- Medical Center of Stomatology, The First Affiliated Hospital, Jinan University, Guangzhou, China
- Chaoshan Hospital, The First Affiliated Hospital of Jinan University, Chaozhou City, China
- *Correspondence: Zejian Li,
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De D, Nayak T, Chowdhury S, Dhal PK. Insights of Host Physiological Parameters and Gut Microbiome of Indian Type 2 Diabetic Patients Visualized via Metagenomics and Machine Learning Approaches. Front Microbiol 2022; 13:914124. [PMID: 35923393 PMCID: PMC9340226 DOI: 10.3389/fmicb.2022.914124] [Citation(s) in RCA: 7] [Impact Index Per Article: 2.3] [Reference Citation Analysis] [Abstract] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/06/2022] [Accepted: 06/13/2022] [Indexed: 11/13/2022] Open
Abstract
Type 2 diabetes (T2D) is a serious public health issue and may also contribute to modification in the structure of the intestinal microbiota, implying a link between T2D and microbial inhabitants in the digestive tract. This work aimed to develop efficient models for identifying essential physiological markers for improved T2D classification using machine learning algorithms. Using amplicon metagenomic approaches, an effort has also been made to understand the alterations in core gut microbial members in Indian T2D patients with respect to their control normal glucose tolerance (NGT). Our data indicate the level of fasting blood glucose (FBG) and glycated hemoglobin (HbA1c) were the most useful physiological indicators while random forest and support vector machine with RBF Kernel were effective predictions models for identifications of T2D. The dominating gut microbial members Allopreotella, Rikenellaceae RC9 gut group, Haemophilus, Ruminococcus torques group, etc. in Indian T2D patients showed a strong association with both FBG and HbA1c. These members have been reported to have a crucial role in gut barrier breakdown, blood glucose, and lipopolysaccharide level escalation, or as biomarkers. While the dominant NGT microbiota (Akkermansia, Ligilactobacillus, Enterobacter, etc.) in the colon has been shown to influence inflammatory immune responses by acting as an anti-inflammatory agent and maintaining the gut barrier. The topology study of co-occurrence network analysis indicates that changes in network complexity in T2D lead to variations in the different gut microbial members compared to NGT. These studies provide a better understanding of the gut microbial diversity in Indian T2D patients and show the way for the development of valuable diagnostics strategies to improve the prediction and modulation of the T2D along with already established methods.
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Affiliation(s)
- Debjit De
- Department of Life Science and Biotechnology, Jadavpur University, Kolkata, India
| | - Tilak Nayak
- Department of Life Science and Biotechnology, Jadavpur University, Kolkata, India
| | - Subhankar Chowdhury
- Department of Endocrinology, Institute of Post Graduate Medical Education and Research (IPGMER) and SSKM Hospital, Kolkata, India
| | - Paltu Kumar Dhal
- Department of Life Science and Biotechnology, Jadavpur University, Kolkata, India
- *Correspondence: Paltu Kumar Dhal
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Qin H, Li G, Xu X, Zhang C, Zhong W, Xu S, Yin Y, Song J. The role of oral microbiome in periodontitis under diabetes mellitus. J Oral Microbiol 2022; 14:2078031. [PMID: 35694215 PMCID: PMC9176325 DOI: 10.1080/20002297.2022.2078031] [Citation(s) in RCA: 39] [Impact Index Per Article: 13.0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/17/2022] Open
Abstract
Periodontitis is among most common human inflammatory diseases and characterized by destruction of tooth-supporting tissues that will eventually lead to tooth loss. Diabetes mellitus (DM) is a group of metabolic disorders characterized by chronic hyperglycemia which results from defects in insulin secretion and/or insulin resistance. Numerous studies have provided evidence for the inter-relationship between DM and periodontitis that has been considered as the sixth most frequent complication of DM. However, the mechanisms are not fully understood yet. The impact of DM on periodontitis through hyperglycemia and inflammatory pathways is well described, but the effects of DM on oral microbiota remain controversial according to previous studies. Recent studies using next-generation sequencing technology indicate that DM can alter the biodiversity and composition of oral microbiome especially subgingival microbiome. This may be another mechanism by which DM risks or aggravates periodontitis. Thus, to understand the role of oral microbiome in periodontitis of diabetics and the mechanism of shifts of oral microbiome under DM would be valuable for making specific therapeutic regimens for treating periodontitis patients with DM or preventing diabetic patients from periodontitis. This article reviews the role of oral microbiome in periodontal health (symbiosis) and disease (dysbiosis), highlights the oral microbial shifts under DM and summarizes the mechanism of the shifts.
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Affiliation(s)
- Han Qin
- College of Stomatology, Chongqing Medical University, Chongqing, Unknown, China
- Chongqing Key Laboratory of Oral Diseases and Biomedical Sciences, Chongqing, Unknown, China
- Chongqing Municipal Key Laboratory of Oral Biomedical Engineering of Higher Education, Chongqing, Unknown, China
| | - Guangyue Li
- College of Stomatology, Chongqing Medical University, Chongqing, Unknown, China
- Chongqing Key Laboratory of Oral Diseases and Biomedical Sciences, Chongqing, Unknown, China
- Chongqing Municipal Key Laboratory of Oral Biomedical Engineering of Higher Education, Chongqing, Unknown, China
| | - Xiaohui Xu
- College of Stomatology, Chongqing Medical University, Chongqing, Unknown, China
- Chongqing Key Laboratory of Oral Diseases and Biomedical Sciences, Chongqing, Unknown, China
- Chongqing Municipal Key Laboratory of Oral Biomedical Engineering of Higher Education, Chongqing, Unknown, China
| | - Chuangwei Zhang
- College of Stomatology, Chongqing Medical University, Chongqing, Unknown, China
- Chongqing Key Laboratory of Oral Diseases and Biomedical Sciences, Chongqing, Unknown, China
- Chongqing Municipal Key Laboratory of Oral Biomedical Engineering of Higher Education, Chongqing, Unknown, China
| | - Wenjie Zhong
- College of Stomatology, Chongqing Medical University, Chongqing, Unknown, China
- Chongqing Key Laboratory of Oral Diseases and Biomedical Sciences, Chongqing, Unknown, China
- Chongqing Municipal Key Laboratory of Oral Biomedical Engineering of Higher Education, Chongqing, Unknown, China
| | - Shihan Xu
- College of Stomatology, Chongqing Medical University, Chongqing, Unknown, China
- Chongqing Key Laboratory of Oral Diseases and Biomedical Sciences, Chongqing, Unknown, China
- Chongqing Municipal Key Laboratory of Oral Biomedical Engineering of Higher Education, Chongqing, Unknown, China
| | - Yuanyuan Yin
- College of Stomatology, Chongqing Medical University, Chongqing, Unknown, China
- Chongqing Key Laboratory of Oral Diseases and Biomedical Sciences, Chongqing, Unknown, China
- Chongqing Municipal Key Laboratory of Oral Biomedical Engineering of Higher Education, Chongqing, Unknown, China
| | - Jinlin Song
- College of Stomatology, Chongqing Medical University, Chongqing, Unknown, China
- Chongqing Key Laboratory of Oral Diseases and Biomedical Sciences, Chongqing, Unknown, China
- Chongqing Municipal Key Laboratory of Oral Biomedical Engineering of Higher Education, Chongqing, Unknown, China
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Guo XJ, Jiang T, Ma XX, Hu XJ, Huang JB, Cui LT, Cui J, Yao XH, Shi YL, Li J, Guo ZL, Lou JD, Liang MC, Fu HY, Yuan P, Liu JY, Tu LP, Xu JT. Relationships Between Diurnal Changes of Tongue Coating Microbiota and Intestinal Microbiota. Front Cell Infect Microbiol 2022; 12:813790. [PMID: 35433494 PMCID: PMC9008461 DOI: 10.3389/fcimb.2022.813790] [Citation(s) in RCA: 10] [Impact Index Per Article: 3.3] [Reference Citation Analysis] [Abstract] [MESH Headings] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/12/2021] [Accepted: 03/02/2022] [Indexed: 11/29/2022] Open
Abstract
The oral cavity and the intestine are the main distribution locations of human digestive bacteria. Exploring the relationships between the tongue coating and gut microbiota, the influence of the diurnal variations of the tongue coating microbiota on the intestinal microbiota can provide a reference for the development of the disease diagnosis and monitoring, as well as the medication time. In this work, a total of 39 healthy college students were recruited. We collected their tongue coating microbiota which was collected before and after sleep and fecal microbiota. The diurnal variations of tongue coating microbiota are mainly manifested on the changes in diversity and relative abundance. There are commensal bacteria in the tongue coating and intestines, especially Prevotella which has the higher proportion in both sites. The relative abundance of Prevotella in the tongue coating before sleep has a positive correlation with intestinal Prevotella; the r is 0.322 (p < 0.05). Bacteroides in the intestine had the most bacteria associated with the tongue coating and had the highest correlation coefficient with Veillonella in the oral cavity, which was 0.468 (p < 0.01). These results suggest that the abundance of the same flora in the two sites may have a common change trend. The SourceTracker results show that the proportion of intestinal bacteria sourced from tongue coating is less than 1%. It indicates that oral flora is difficult to colonize in the intestine in healthy people. This will provide a reference for the study on the oral and intestinal microbiota in diseases.
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Affiliation(s)
- Xiao-jing Guo
- Basic Medical College, Shanghai University of Traditional Chinese Medicine (TCM), Shanghai, China
| | - Tao Jiang
- Basic Medical College, Shanghai University of Traditional Chinese Medicine (TCM), Shanghai, China
| | - Xu-xiang Ma
- Basic Medical College, Shanghai University of Traditional Chinese Medicine (TCM), Shanghai, China
| | - Xiao-juan Hu
- Shanghai Collaborative Innovation Center of Health Service in Traditional Chinese Medicine (TCM), Shanghai University of Traditional Chinese Medicine (TCM), Shanghai, China
| | - Jing-bin Huang
- Basic Medical College, Shanghai University of Traditional Chinese Medicine (TCM), Shanghai, China
| | - Long-tao Cui
- Basic Medical College, Shanghai University of Traditional Chinese Medicine (TCM), Shanghai, China
| | - Ji Cui
- Basic Medical College, Shanghai University of Traditional Chinese Medicine (TCM), Shanghai, China
| | - Xing-hua Yao
- Basic Medical College, Shanghai University of Traditional Chinese Medicine (TCM), Shanghai, China
| | - Yu-lin Shi
- Basic Medical College, Shanghai University of Traditional Chinese Medicine (TCM), Shanghai, China
| | - Jun Li
- Basic Medical College, Shanghai University of Traditional Chinese Medicine (TCM), Shanghai, China
| | - Zhi-ling Guo
- Basic Medical College, Shanghai University of Traditional Chinese Medicine (TCM), Shanghai, China
| | - Jin-di Lou
- Basic Medical College, Shanghai University of Traditional Chinese Medicine (TCM), Shanghai, China
| | - Meng-chen Liang
- Basic Medical College, Shanghai University of Traditional Chinese Medicine (TCM), Shanghai, China
| | - Hong-yuan Fu
- Basic Medical College, Shanghai University of Traditional Chinese Medicine (TCM), Shanghai, China
| | - Pei Yuan
- Basic Medical College, Shanghai University of Traditional Chinese Medicine (TCM), Shanghai, China
| | - Jia-yi Liu
- Basic Medical College, Shanghai University of Traditional Chinese Medicine (TCM), Shanghai, China
| | - Li-ping Tu
- Basic Medical College, Shanghai University of Traditional Chinese Medicine (TCM), Shanghai, China
- *Correspondence: Li-ping Tu, ; Jia-tuo Xu,
| | - Jia-tuo Xu
- Basic Medical College, Shanghai University of Traditional Chinese Medicine (TCM), Shanghai, China
- *Correspondence: Li-ping Tu, ; Jia-tuo Xu,
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Tsai FT, Wang DH, Yang CC, Lin YC, Huang LJ, Tsai WY, Li CW, Hsu WE, Tu HF, Hsu ML. Locational effects on oral microbiota among long-term care patients. J Oral Microbiol 2022; 14:2033003. [PMID: 35186212 PMCID: PMC8856053 DOI: 10.1080/20002297.2022.2033003] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/16/2022] Open
Abstract
Background Dysbiosis of oral microbiota is the cause of many diseases related to oral and general health. However, few Asia-based studies have evaluated the role of oral microbiota in patients receiving long-term care. Thus, new indications are needed for early prevention and risk management based on information derived from the oral microbiota. Methods We used next-generation sequencing (NGS) to identify the oral bacterial composition and abundance in patients receiving long-term care: 20 from the outpatient department (OPD) and 20 home-care patients. Their microbial compositions, taxonomy, and alpha/beta diversity were characterized. Results Microbiota from the two groups showed different diversity and homogeneity, as well as distinct bacterial species. A more diverse and stable microbial population was observed among OPD patients. Our findings indicated that home-care patients had a higher risk of oral diseases due to the existence of dominant species and a less stable microbial community. Conclusion This work was the first in Taiwan to use NGS to investigate the oral microbiota of long-term care patients. Our study demonstrated the potential use of dominant bacterial species as biomarkers for the risk management of posttreatment complications.
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Affiliation(s)
- Fa-Tzu Tsai
- Institute of Oral Biology, National Yang Ming Chiao Tung University, Taipei, Taiwan
| | - Ding-Han Wang
- Department of Dentistry, National Yang Ming Chiao Tung University, Taipei, Taiwan
| | - Cheng-Chieh Yang
- Department of Dentistry, National Yang Ming Chiao Tung University, Taipei, Taiwan
- Department of Stomatology, Oral & Maxillofacial Surgery, Taipei Veterans General Hospital, Taipei, Taiwan
| | - Yu-Cheng Lin
- Department of Dentistry, National Yang Ming Chiao Tung University, Taipei, Taiwan
| | - Lin-Jack Huang
- Department of Dentistry, National Yang Ming Chiao Tung University Hospital, Yilan, Taiwan
| | - Wei-Yu Tsai
- Department of Dentistry, National Yang Ming Chiao Tung University Hospital, Yilan, Taiwan
| | - Chang-Wei Li
- Department of Biological Science and Technology, National Yang Ming Chiao Tung University, Hsinchu, Taiwan
| | - Wun-Eng Hsu
- Department of Dentistry, Far Eastern Memorial Hospital, New Taipei City, Taiwan
| | - Hsi-Feng Tu
- Department of Dentistry, National Yang Ming Chiao Tung University, Taipei, Taiwan
- Department of Dentistry, National Yang Ming Chiao Tung University Hospital, Yilan, Taiwan
| | - Ming-Lun Hsu
- Department of Dentistry, National Yang Ming Chiao Tung University, Taipei, Taiwan
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Gao C, Guo Y, Chen F. Cross-Cohort Microbiome Analysis of Salivary Biomarkers in Patients With Type 2 Diabetes Mellitus. Front Cell Infect Microbiol 2022; 12:816526. [PMID: 35145929 PMCID: PMC8821939 DOI: 10.3389/fcimb.2022.816526] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Abstract] [MESH Headings] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/16/2021] [Accepted: 01/10/2022] [Indexed: 01/22/2023] Open
Abstract
Several studies have ascertained differences in salivary microbiota between patients with type 2 diabetes mellitus (T2DM) and healthy populations. However, the predictive accuracy and reproducibility of these 16S rRNA sequencing analyses when applied to other cohorts remain enigmatic. A comprehensive analysis was conducted on the included 470 samples from five researches in publicly available databases. The discrepancy and predictive accuracy of salivary microbiota between T2DM patients and healthy populations were evaluated from multiple perspectives, followed by the identification of salivary biomarkers for DM. Next, a classification model (areas under the curves = 0.92) was developed based on a large sample. The model could be used for clinical diagnosis and prognostic monitoring and as a basis for hypothesis-driven mechanistic researches. Furthermore, the research heterogeneity across geographic regions suggested that microbiological markers might not become a uniform clinical standard in human beings. They rather identify abnormal alterations under the microbiological characteristics of a specific population.
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Affiliation(s)
- Chuqi Gao
- Central Laboratory, Peking University School and Hospital of Stomatology, Beijing, China
| | - Ying Guo
- Department of Stomatology, General Hospital of Shenzhen University, Shenzhen, China
| | - Feng Chen
- Central Laboratory, Peking University School and Hospital of Stomatology, Beijing, China
- *Correspondence: Feng Chen,
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Negrini TDC, Carlos IZ, Duque C, Caiaffa KS, Arthur RA. Interplay Among the Oral Microbiome, Oral Cavity Conditions, the Host Immune Response, Diabetes Mellitus, and Its Associated-Risk Factors-An Overview. FRONTIERS IN ORAL HEALTH 2022; 2:697428. [PMID: 35048037 PMCID: PMC8757730 DOI: 10.3389/froh.2021.697428] [Citation(s) in RCA: 33] [Impact Index Per Article: 11.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/19/2021] [Accepted: 08/16/2021] [Indexed: 12/12/2022] Open
Abstract
This comprehensive review of the literature aimed to investigate the interplay between the oral microbiome, oral cavity conditions, and host immune response in Diabetes mellitus (DM). Moreover, this review also aimed to investigate how DM related risk factors, such as advanced age, hyperglycemia, hyperlipidemia, obesity, hypertension and polycystic ovary syndrome (PCOS), act in promoting or modifying specific mechanisms that could potentially perpetuate both altered systemic and oral conditions. We found that poorly controlled glycemic index may exert a negative effect on the immune system of affected individuals, leading to a deficient immune response or to an exacerbation of the inflammatory response exacerbating DM-related complications. Hyperglycemia induces alterations in the oral microbiome since poor glycemic control is associated with increased levels and frequencies of periodontal pathogens in the subgingival biofilm of individuals with DM. A bidirectional relationship between periodontal diseases and DM has been suggested: DM patients may have an exaggerated inflammatory response, poor repair and bone resorption that aggravates periodontal disease whereas the increased levels of systemic pro-inflammatory mediators found in individuals affected with periodontal disease exacerbates insulin resistance. SARS-CoV-2 infection may represent an aggravating factor for individuals with DM. Individuals with DM tend to have low salivary flow and a high prevalence of xerostomia, but the association between prevalence/experience of dental caries and DM is still unclear. DM has also been associated to the development of lesions in the oral mucosa, especially potentially malignant ones and those associated with fungal infections. Obesity plays an important role in the induction and progression of DM. Co-affected obese and DM individuals tend to present worse oral health conditions. A decrease in HDL and, an increase in triglycerides bloodstream levels seem to be associated with an increase on the load of periodontopathogens on oral cavity. Moreover, DM may increase the likelihood of halitosis. Prevalence of impaired taste perception and impaired smell recognition tend to be greater in DM patients. An important interplay among oral cavity microbiome, DM, obesity and hypertension has been proposed as the reduction of nitrate into nitrite, in addition to contribute to lowering of blood pressure, reduces oxidative stress and increases insulin secretion, being these effects desirable for the control of obesity and DM. Women with PCOS tend to present a distinct oral microbial composition and an elevated systemic response to selective members of this microbial community, but the association between oral microbiome, PCOS are DM is still unknown. The results of the studies presented in this review suggest the interplay among the oral microbiome, oral cavity conditions, host immune response and DM and some of the DM associated risk factors exist. DM individuals need to be encouraged and motivated for an adequate oral health care. In addition, these results show the importance of adopting multidisciplinary management of DM and of strengthening physicians-dentists relationship focusing on both systemic and on oral cavity conditions of DM patients.
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Affiliation(s)
- Thais de Cássia Negrini
- Department of Clinical Analysis, School of Pharmaceutical Sciences, São Paulo State University, Araraquara, Brazil
| | - Iracilda Zeppone Carlos
- Department of Clinical Analysis, School of Pharmaceutical Sciences, São Paulo State University, Araraquara, Brazil
| | - Cristiane Duque
- Department of Restorative and Preventive Dentistry, Araçatuba Dental School, São Paulo State University, Araçatuba, Brazil
| | - Karina Sampaio Caiaffa
- Department of Restorative and Preventive Dentistry, Araçatuba Dental School, São Paulo State University, Araçatuba, Brazil
| | - Rodrigo Alex Arthur
- Department of Preventive and Community Dentistry, Dental School, Federal University of Rio Grande do Sul, Porto Alegre, Brazil
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Wang D, Liu J, Zhou L, Zhang Q, Li M, Xiao X. Effects of Oral Glucose-Lowering Agents on Gut Microbiota and Microbial Metabolites. Front Endocrinol (Lausanne) 2022; 13:905171. [PMID: 35909556 PMCID: PMC9326154 DOI: 10.3389/fendo.2022.905171] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 03/26/2022] [Accepted: 06/14/2022] [Indexed: 11/30/2022] Open
Abstract
The current research and existing facts indicate that type 2 diabetes mellitus (T2DM) is characterized by gut microbiota dysbiosis and disturbed microbial metabolites. Oral glucose-lowering drugs are reported with pleiotropic beneficial effects, including not only a decrease in glucose level but also weight loss, antihypertension, anti-inflammation, and cardiovascular protection, but the underlying mechanisms are still not clear. Evidence can be found showing that oral glucose-lowering drugs might modify the gut microbiome and thereby alter gastrointestinal metabolites to improve host health. Although the connections among gut microbial communities, microbial metabolites, and T2DM are complex, figuring out how antidiabetic agents shape the gut microbiome is vital for optimizing the treatment, meaningful for the instruction for probiotic therapy and gut microbiota transplantation in T2DM. In this review, we focused on the literatures in gut microbiota and its metabolite profile alterations beneficial from oral antidiabetic drugs, trying to provide implications for future study in the developing field of these drugs, such as combination therapies, pre- and probiotics intervention in T2DM, and subjects with pregestational diabetes and gestational diabetes mellitus.
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Affiliation(s)
- Dongmei Wang
- Department of Endocrinology, National Health Commission (NHC) Key Laboratory of Endocrinology, Chinese Academy of Medical Sciences, Peking Union Medical College Hospital, Peking Union Medical College, Beijing, China
| | - Jieying Liu
- Department of Endocrinology, National Health Commission (NHC) Key Laboratory of Endocrinology, Chinese Academy of Medical Sciences, Peking Union Medical College Hospital, Peking Union Medical College, Beijing, China
- Department of Medical Research Center, Chinese Academy of Medical Sciences, Peking Union Medical College Hospital, Peking Union Medical College, Beijing, China
| | - Liyuan Zhou
- Department of Endocrinology, National Health Commission (NHC) Key Laboratory of Endocrinology, Chinese Academy of Medical Sciences, Peking Union Medical College Hospital, Peking Union Medical College, Beijing, China
| | - Qian Zhang
- Department of Endocrinology, National Health Commission (NHC) Key Laboratory of Endocrinology, Chinese Academy of Medical Sciences, Peking Union Medical College Hospital, Peking Union Medical College, Beijing, China
| | - Ming Li
- Department of Endocrinology, National Health Commission (NHC) Key Laboratory of Endocrinology, Chinese Academy of Medical Sciences, Peking Union Medical College Hospital, Peking Union Medical College, Beijing, China
| | - Xinhua Xiao
- Department of Endocrinology, National Health Commission (NHC) Key Laboratory of Endocrinology, Chinese Academy of Medical Sciences, Peking Union Medical College Hospital, Peking Union Medical College, Beijing, China
- *Correspondence: Xinhua Xiao,
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Huang Q, Meng L, Li H, Xiong N, Zeng L, Wang G, Zhang P, Zhao H, Liu D. Huoxue Jiangtang Decoction Alleviates Type 2 Diabetes Mellitus by Regulating the Oral Microbiota and Food Preferences. Diabetes Metab Syndr Obes 2022; 15:3739-3751. [PMID: 36474726 PMCID: PMC9719691 DOI: 10.2147/dmso.s391226] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Grants] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 10/17/2022] [Accepted: 11/24/2022] [Indexed: 11/30/2022] Open
Abstract
PURPOSE As a formula of traditional Chinese medicine (TCM), Huoxue Jiangtang Decoction (HJD) has positive effects on diabetes mellitus (DM) through improving of the metabolism of glycolipid and the function of β-cell. Hence, this research aims to explore the potential therapeutic effects of HJD on diabetes and reveal its underlying mechanisms. METHODS Diabetic rat models induced by high-fat diet (HFD) and streptozotocin (STZ) were included in this study. Following successful modeling, diabetic rats were treated with HJD, and then its therapeutic effects in eight weeks were evaluated. In addition to biochemical indicators, two-bottle preference tests were carried out to examine the rats' preferences for fat and sugar, and 16S rRNA gene sequencing was performed to disclose the differences of oral microbiota among groups. Finally, Pearson correlation coefficient was used to explore the correlation between oral microbiota and the preferences for fat and sugar. RESULTS It was found that HJD significantly improved the levels of fasting blood glucose (FBG), glucose tolerance, and dyslipidemia. Additionally, HJD contributed to decreasing preferences for fat and sugar in diabetic rats, which plays an important role in food intake. Furthermore, HJD regulated the abundance, distribution, and structure of oral microbiota in diabetic rats, serving as one of the underlying mechanisms of its antidiabetic effects. CONCLUSION Taken with other formulas, HJD functions to improve the metabolism of glycolipid and the function of β-cell by inhibiting preferences for fat and sugar, as well as regulating the oral microbiota of diabetic rats. Furthermore, a potential correlation between the oral micro-environment and preferences for fat and sugar in STZ-induced diabetic rats is likely to exist.
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Affiliation(s)
- Qian Huang
- The Fourth Clinical Medical College of Guangzhou University of Chinese Medicine, Shenzhen, People’s Republic of China
- Department of Endocrinology, Shenzhen Traditional Chinese Medicine Hospital, Shenzhen, People’s Republic of China
| | - Lu Meng
- The Fourth Clinical Medical College of Guangzhou University of Chinese Medicine, Shenzhen, People’s Republic of China
- Department of Endocrinology, Shenzhen Traditional Chinese Medicine Hospital, Shenzhen, People’s Republic of China
| | - Huilin Li
- Department of Endocrinology, Shenzhen Traditional Chinese Medicine Hospital, Shenzhen, People’s Republic of China
| | - Ni Xiong
- The Fourth Clinical Medical College of Guangzhou University of Chinese Medicine, Shenzhen, People’s Republic of China
- Department of Endocrinology, Shenzhen Traditional Chinese Medicine Hospital, Shenzhen, People’s Republic of China
| | - Lin Zeng
- The Fourth Clinical Medical College of Guangzhou University of Chinese Medicine, Shenzhen, People’s Republic of China
- Department of Endocrinology, Shenzhen Traditional Chinese Medicine Hospital, Shenzhen, People’s Republic of China
| | - Gaoxiang Wang
- Department of Endocrinology, Shenzhen Traditional Chinese Medicine Hospital, Shenzhen, People’s Republic of China
- Shenzhen Traditional Chinese Medicine Hospital Affiliated to Nanjing University of Chinese Medicine, Shenzhen, People’s Republic of China
| | - Pengxiang Zhang
- The Fourth Clinical Medical College of Guangzhou University of Chinese Medicine, Shenzhen, People’s Republic of China
- Department of Endocrinology, Shenzhen Traditional Chinese Medicine Hospital, Shenzhen, People’s Republic of China
| | - Hengxia Zhao
- Department of Endocrinology, Shenzhen Traditional Chinese Medicine Hospital, Shenzhen, People’s Republic of China
| | - Deliang Liu
- Department of Endocrinology, Shenzhen Traditional Chinese Medicine Hospital, Shenzhen, People’s Republic of China
- Correspondence: Deliang Liu, Department of Endocrinology, Shenzhen Traditional Chinese Medicine Hospital, 1# Fuhua Road, Futian District, Shenzhen, 518033, People’s Republic of China, Tel +86 13924610289, Fax +86 755-88358328-3319, Email
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Rungrueang K, Yuma S, Tantipoj C, Khovidhunkit SOP, Fuangtharnthip P, Thuramonwong T, Suwattipong M, Supa-amornkul S. Oral Bacterial Microbiomes in Association with Potential Prediabetes Using Different Criteria of Diagnosis. INTERNATIONAL JOURNAL OF ENVIRONMENTAL RESEARCH AND PUBLIC HEALTH 2021; 18:7436. [PMID: 34299886 PMCID: PMC8307246 DOI: 10.3390/ijerph18147436] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.5] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Subscribe] [Scholar Register] [Received: 06/14/2021] [Revised: 07/08/2021] [Accepted: 07/08/2021] [Indexed: 12/22/2022]
Abstract
This study aimed to find a potential biomarker that can be used to diagnose prediabetic condition by comparing the salivary bacterial microbiomes between Thai dental patients with normoglycemia (NG) and those with potential prediabetes (PPG) conditions. Thirty-three subjects were randomly recruited. Demographic data were collected along with oral examination and unstimulated salivary collections. The salivary bacterial microbiomes were identified by high-throughput sequencing on the V3-V4 region of the bacterial 16S rRNA gene. Microbiomes in this study were composed of 12 phyla, 19 classes, 29 orders, 56 families, 81 genera, and 184 species. To check the validity of the selection criterion for prediabetes, we adopted two separate criteria to divide samples into PPG and NG groups using glycated hemoglobin A1c (HbA1c) or fasting plasma glucose (FPG) levels. Using the HbA1c level resulted in the significant reduction of Alloprevotella, Neisseria, Rothia, and Streptococcus abundances in PPG compared with those in NG (p-value < 0.05). On the other hand, the abundance of Absconditabacteriales was significantly reduced whereas Leptotrichia, Stomatobaculum, and Ruminococcaceae increased in the PPG group when the samples were classified by the FPG level (p-value < 0.05). It is implied that the group classifying criterion should be carefully concerned when investigating relative abundances between groups. However, regardless of the criteria, Rothia is significantly dominant in the NG groups, suggesting that Rothia might be a potential prediabetic biomarker. Due to the small sample size of this study, further investigation with a larger sample size is necessary to ensure that Rothia can be a potential biomarker for prediabetes in Thai people.
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Affiliation(s)
- Kornwipa Rungrueang
- Residency Training Program, Department of Advanced General Dentistry, Faculty of Dentistry, Mahidol University, Bangkok 10400, Thailand;
| | - Suraphong Yuma
- Department of Physics, Faculty of Science, Mahidol University, Bangkok 10400, Thailand;
| | - Chanita Tantipoj
- Department of Advanced General Dentistry, Faculty of Dentistry, Mahidol University, Bangkok 10400, Thailand; (C.T.); (S.-o.P.K.); (P.F.)
| | | | - Pornpoj Fuangtharnthip
- Department of Advanced General Dentistry, Faculty of Dentistry, Mahidol University, Bangkok 10400, Thailand; (C.T.); (S.-o.P.K.); (P.F.)
| | - Thitima Thuramonwong
- Dental Hospital, Faculty of Dentistry, Mahidol University, Bangkok 10400, Thailand; (T.T.); (M.S.)
| | - Muneedej Suwattipong
- Dental Hospital, Faculty of Dentistry, Mahidol University, Bangkok 10400, Thailand; (T.T.); (M.S.)
| | - Sirirak Supa-amornkul
- Mahidol International Dental School, Faculty of Dentistry, Mahidol University, Bangkok 10400, Thailand
- Pornchai Matangkasombut Center for Microbial Genomic, Faculty of Science, Mahidol University, Bangkok 10400, Thailand
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Chen X, Daliri EBM, Tyagi A, Oh DH. Cariogenic Biofilm: Pathology-Related Phenotypes and Targeted Therapy. Microorganisms 2021; 9:microorganisms9061311. [PMID: 34208588 PMCID: PMC8234214 DOI: 10.3390/microorganisms9061311] [Citation(s) in RCA: 21] [Impact Index Per Article: 5.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/17/2021] [Revised: 06/06/2021] [Accepted: 06/14/2021] [Indexed: 01/02/2023] Open
Abstract
The initiation and development of cariogenic (that is, caries-related) biofilms are the result of the disruption of homeostasis in the oral microenvironment. There is a daily accumulation of dental biofilm on the surface of teeth and its matrix of extracellular polymers supports the host in its defense against invading microbes, thus helping to achieve oral microbial homeostasis. However, the homeostasis can be broken down under certain circumstances such as during long-term exposure to a low pH environment which results in the dominance of acidogenic and acid-tolerating species in the dental biofilm and, thus, triggers the shift of harmless biofilm to an acidic one. This work aims to explore microbial diversity and the quorum sensing of dental biofilm and their important contributions to oral health and disease. The complex and multispecies ecosystems of the cariogenic biofilm pose significant challenges for the modulation of the oral microenvironment. Promising treatment strategies are those that target cariogenic niches with high specificity without disrupting the balance of the surrounding oral microbiota. Here, we summarized the recent advances in modulating cariogenic biofilm and/or controlling its pathogenic traits.
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Zhao F, Dong T, Yuan KY, Wang NJ, Xia FZ, Liu D, Wang ZM, Ma R, Lu YL, Huang ZW. Shifts in the Bacterial Community of Supragingival Plaque Associated With Metabolic-Associated Fatty Liver Disease. Front Cell Infect Microbiol 2020; 10:581888. [PMID: 33384967 PMCID: PMC7770214 DOI: 10.3389/fcimb.2020.581888] [Citation(s) in RCA: 13] [Impact Index Per Article: 2.6] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/01/2020] [Accepted: 11/05/2020] [Indexed: 11/13/2022] Open
Abstract
Metabolic-associated fatty liver disease (MAFLD), also known as the hepatic manifestation of metabolic disorders, has become one of the most common chronic liver diseases worldwide. The associations between some oral resident microbes and MAFLD have been described. However, changes to the oral microbial community in patients with MAFLD remain unknown. In this study, variations to the supragingival microbiota of MAFLD patients were identified. The microbial genetic profile of supragingival plaque samples from 24 MAFLD patients and 22 healthy participants were analyzed by 16S rDNA sequencing and bioinformatics analysis. Clinical variables, including indicators of insulin resistance, obesity, blood lipids, and hepatocellular damage, were evaluated with laboratory tests and physical examinations. The results showed that the diversity of the supragingival microbiota in MAFLD patients was significantly higher than that in healthy individuals. Weighted UniFrac principal coordinates analysis and partial least squares discriminant analysis showed that the samples from the MAFLD and control groups formed separate clusters (Adonis, P = 0.0120). There were 27 taxa with differential distributions (linear discriminant analysis, LDA>2.0) between two groups, among which Actinomyces spp. and Prevotella 2 spp. were over-represented in the MAFLD group with highest LDA score, while Neisseria spp. and Bergeyella spp. were more abundant in the control group. Co-occurrence networks of the top 50 abundant genera in the two groups suggested that the inter-genera relationships were also altered in the supragingival plaque of MAFLD patients. In addition, in genus level, as risk factors for the development of MAFLD, insulin resistance was positively correlated with the abundances of Granulicatella, Veillonella, Streptococcus, and Scardovia, while obesity was positively correlated to the abundances of Streptococcus, Oslenella, Scardovia, and Selenomonas. Metagenomic predictions based on Phylogenetic Investigation of Communities by Reconstruction of Unobserved States revealed that pathways related to sugar (mainly free sugar) metabolism were enriched in the supragingival plaque of the MAFLD group. In conclusion, as compared to healthy individuals, component and interactional dysbioses were observed in the supragingival microbiota of the MAFLD group.
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Affiliation(s)
- Fen Zhao
- Department of Endodontics, Shanghai Ninth People’s Hospital, College of Stomatology, Shanghai Jiao Tong University School of Medicine, Shanghai, China
- National Clinical Research Center for Oral Diseases, Shanghai, China
- Shanghai Key Laboratory of Stomatology & Shanghai Research Institute of Stomatology, Shanghai, China
| | - Ting Dong
- Department of Endodontics, Shanghai Ninth People’s Hospital, College of Stomatology, Shanghai Jiao Tong University School of Medicine, Shanghai, China
- National Clinical Research Center for Oral Diseases, Shanghai, China
- Shanghai Key Laboratory of Stomatology & Shanghai Research Institute of Stomatology, Shanghai, China
| | - Ke-Yong Yuan
- Department of Endodontics, Shanghai Ninth People’s Hospital, College of Stomatology, Shanghai Jiao Tong University School of Medicine, Shanghai, China
- National Clinical Research Center for Oral Diseases, Shanghai, China
- Shanghai Key Laboratory of Stomatology & Shanghai Research Institute of Stomatology, Shanghai, China
| | - Ning-Jian Wang
- Institute and Department of Endocrinology and Metabolism, Shanghai Ninth People’s Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai, China
| | - Fang-Zhen Xia
- Institute and Department of Endocrinology and Metabolism, Shanghai Ninth People’s Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai, China
| | - Di Liu
- Computational Virology Group, Center for Bacteria and Viruses Resources and Bioinformation, Wuhan Institute of Virology, Chinese Academy of Sciences, Wuhan, China
- University of Chinese Academy of Sciences, Beijing, China
| | - Zhi-Min Wang
- Shanghai-MOST Key Laboratory of Health and Disease Genomics, Chinese National Human Genome Center, Shanghai, China
| | - Rui Ma
- Department of Endodontics, Shanghai Ninth People’s Hospital, College of Stomatology, Shanghai Jiao Tong University School of Medicine, Shanghai, China
- National Clinical Research Center for Oral Diseases, Shanghai, China
- Shanghai Key Laboratory of Stomatology & Shanghai Research Institute of Stomatology, Shanghai, China
| | - Ying-Li Lu
- Institute and Department of Endocrinology and Metabolism, Shanghai Ninth People’s Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai, China
| | - Zheng-Wei Huang
- Department of Endodontics, Shanghai Ninth People’s Hospital, College of Stomatology, Shanghai Jiao Tong University School of Medicine, Shanghai, China
- National Clinical Research Center for Oral Diseases, Shanghai, China
- Shanghai Key Laboratory of Stomatology & Shanghai Research Institute of Stomatology, Shanghai, China
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Li WZ, Stirling K, Yang JJ, Zhang L. Gut microbiota and diabetes: From correlation to causality and mechanism. World J Diabetes 2020; 11:293-308. [PMID: 32843932 PMCID: PMC7415231 DOI: 10.4239/wjd.v11.i7.293] [Citation(s) in RCA: 90] [Impact Index Per Article: 18.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 02/29/2020] [Revised: 05/21/2020] [Accepted: 06/10/2020] [Indexed: 02/05/2023] Open
Abstract
In this review, we summarize the recent microbiome studies related to diabetes disease and discuss the key findings that show the early emerging potential causal roles for diabetes. On a global scale, diabetes causes a significant negative impact to the health status of human populations. This review covers type 1 diabetes and type 2 diabetes. We examine promising studies which lead to a better understanding of the potential mechanism of microbiota in diabetes diseases. It appears that the human oral and gut microbiota are deeply interdigitated with diabetes. It is that simple. Recent studies of the human microbiome are capturing the attention of scientists and healthcare practitioners worldwide by focusing on the interplay of gut microbiome and diabetes. These studies focus on the role and the potential impact of intestinal microflora in diabetes. We paint a clear picture of how strongly microbes are linked and associated, both positively and negatively, with the fundamental and essential parts of diabetes in humans. The microflora seems to have an endless capacity to impact and transform diabetes. We conclude that there is clear and growing evidence of a close relationship between the microbiota and diabetes and this is worthy of future investments and research efforts.
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Affiliation(s)
- Wei-Zheng Li
- Microbiome-X, Beijing Advanced Innovation Center for Big Data-Based Precision Medicine, School of Medicine and Engineering, Key Laboratory of Big Data-Based Precision Medicine, Beihang University, Beijing 100191, China
- School of Biological Science and Medical Engineering, Beihang University, Beijing 100191, China
| | - Kyle Stirling
- Luddy School of Informatics, Computing and Engineering, Indiana University, Bloomington, IN 47408, United States
- The Crisis Technologies Innovation Lab, Indiana University, The Information Technology Services and the Pervasive Technology Institute, Bloomington, IN 47408, United States
- Shandong Institute of Industrial Technology for Health Sciences and Precision Medicine, Jinan 250000, Shandong Province, China
| | - Jun-Jie Yang
- College of Life Science, Qilu Normal University, Jinan 250000, Shandong Province, China
- Microbiome Research Center, Shandong Institutes for Food and Drug Control, Jinan 250000, Shandong Province, China
- Shandong Children’s Microbiome Center, Qilu Children's Hospital of Shandong University, Jinan 250000, Shandong Province, China
- Microbiological Laboratory, Lin Yi People’s Hospital, Linyi 276000, Shandong Province, China
- Qingdao Human Microbiome Center, The Affiliated Central Hospital of Qingdao University, Qingdao 266000, Shandong Province, China
| | - Lei Zhang
- Microbiome-X, Beijing Advanced Innovation Center for Big Data-Based Precision Medicine, School of Medicine and Engineering, Key Laboratory of Big Data-Based Precision Medicine, Beihang University, Beijing 100191, China
- Shandong Institute of Industrial Technology for Health Sciences and Precision Medicine, Jinan 250000, Shandong Province, China
- Institute for Medical Dataology, Cheeloo College of Medicine, Shandong University, Jinan 250000, Shandong Province, China
- Department of Biostatistics, School of Public Health, Cheeloo College of Medicine, Shandong University, Jinan 250000, Shandong Province, China
- Shandong Children’s Microbiome Center, Research Institute of Pediatrics, Qilu Children's Hospital, Cheeloo College of Medicine, Shandong University, and Jinan Children's Hospital, Jinan 250022, Shandong Province, China
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