Saliva microbiome alterations in dental fluorosis population

In the paper

“Arginine biosynthesis is essentially negatively regulated by ArgR/AhrC family proteins.”

• Also stated in: § Discussion · plain

  “These repressors inhibit arginine synthesis by inhibiting the expression of arginine biosynthetic genes at the transcriptional level [63,64].”

What the sources say

• ?Could not verify

  The available passages labeled Abstract contain bibliographic information, keywords, and the paper title, but no account of how ArgR/AhrC regulates arginine biosynthesis. Searches for negative regulation, arginine biosynthesis, and inhibition of biosynthetic-gene transcription found no passage addressing the claim. (LLM, conf=0.70)

  cites [63] Fulde M, Willenborg J, de Greeff A, et al. ArgR is an essential local transcriptional regulator of the arcABC operon in Streptococcus suis and is crucial for biological fitness in an acidic environment. Microbiology (Reading). 2011; 157: 572– 582. 20947575 sourceExperimental — accuracy not yet measured
• Not checked yetcites [64] Maas WK. The arginine repressor of Escherichia coli. Microbiol Rev. 1994; 58: 631– 640. 7854250 PMC372985

In the paper

“V. metschnikovii is an opportunistic pathogen that rarely causes disease onset in humans”

What the sources say

• ?Could not verify

  The Conclusions and Discussion describe rare human infection by C. pauculus, not V. metschnikovii. Searches for “V. metschnikovii” and “Vibrio metschnikovii” found no passage in our copy addressing the claimed organism. (LLM, conf=0.78)

  cites [51] Huda SA, Yadava S, Kahlown S, et al. A rare case of ventilator-associated pneumonia caused by Cupriavidus Pauculus. Cureus. 2020; 12: e8573. 32670709 PMC7358901 sourceExperimental — accuracy not yet measured
• ?Could not verify

  The Introduction says that Cupriavidus pauculus has rarely been identified as a pathogen in patients, especially immunocompromised patients. A search for “Vibrio metschnikovii” found no passage about that species, so the paper does not verify the claim about V. metschnikovii. (LLM, conf=0.78)

  cites [52] Almasy E, Szederjesi J, Rad P, et al. A fatal case of community acquired Cupriavidus Pauculus Pneumonia. J Crit Care Med (Targu Mures). 2016; 2: 201– 204. 29967861 PMC5953259 sourceExperimental — accuracy not yet measured
• ?Could not verify

  The Introduction and Discussion discuss Cupriavidus pauculus as an opportunistic pathogen, not V. metschnikovii. A search for V. metschnikovii returned no passage addressing whether it rarely causes human disease. (LLM, conf=0.78)

  cites [53] Yahya R, Alyousef W, Omara A, et al. First case of pneumonia caused by Cupriavidus pauculus in an infant in the gulf cooperation council. J Infect Dev Ctries. 2017; 11: 196– 198. 28248683 sourceExperimental — accuracy not yet measured
• Partly supported

  In the discussion of “Vibrio metschnikovii Pneumonia” (page unavailable), the authors explicitly state that human clinical infections are rare. They describe pneumonia in a patient with chronic obstructive pulmonary disease who was taking prednisolone, but do not characterize the bacterium as an opportunistic pathogen or establish that its infections are opportunistic. (LLM, conf=0.82)

  cites [54] Wallet F, Tachon M, Nseir S, et al. Vibrio metschnikovii pneumonia. Emerg Infect Dis. 2005; 11: 1641– 1642. 16355507 PMC3366744 sourceExperimental — accuracy not yet measured

In the paper

“prior work has revealed that certain diseases are associated with changes in the α diversity of the microbiome, while others are not [35–38].”

What the sources say

• ?Could not verify

  The Methods (Statistical Analysis; page unavailable) describe comparisons of overall oral microbiome composition, and the Results (page unavailable) report no case–control difference in those measures. The Methods (Measurements; page unavailable) mention within-subject diversity indices only for quality control. Our copy does not report whether pancreatic cancer, or other diseases, are associated with changes in alpha diversity (searched: alpha diversity, Shannon, Simpson, cases and controls). (LLM, conf=0.76)

  cites [35] Fan X, Alekseyenko AV, Wu J, et al. Human oral microbiome and prospective risk for pancreatic cancer: a population-based nested case-control study. Gut. 2018; 67: 120– 127. 27742762 PMC5607064 sourceExperimental — accuracy not yet measured
• Partly supported

  In “PPP Patients Have Dysbiosis of Oral Microbiota,” the paper reports no significant difference in oral microbiome α-diversity between patients with palmoplantar pustulosis and healthy controls. This supports the claim that some diseases are not associated with a detected change in α-diversity, but the paper does not establish the contrasting claim that other diseases are associated with such changes. (LLM, conf=0.87)

  cites [36] Kageyama Y, Shimokawa Y, Kawauchi K, et al. Dysbiosis of oral microbiota associated with palmoplantar pustulosis. Dermatology. 2021; 237: 347– 356. 33279897 PMC8117382 sourceExperimental — accuracy not yet measured
• ?Not checked — no full text of the sourcecites [37] Wang J, Qian T, Jiang J, et al. Gut microbial profile in biliary atresia: a case-control study. J Gastroenterol Hepatol. 2020; 35: 334– 342. 31271681 source
• Partly supported

  The Results (§3.2.2) report significantly lower Shannon α-diversity in breast cancer patients than in healthy controls. The Chao1 index was not significantly different in those same groups, but the paper does not identify a disease unassociated with changes in α-diversity. It therefore supports only the first part of the broader claim. (LLM, conf=0.85)

  cites [38] Bobin-Dubigeon C, Luu HT, Leuillet S, et al. Faecal microbiota composition varies between patients with breast cancer and healthy women: a comparative case-control study. Nutrients. 2021; 13: 2705. 34444865 PMC8399700 sourceExperimental — accuracy not yet measured

In the paper

“The makeup of the oral microbiota is closely associated with both oral and systemic health”

What the sources say

• ?Not checked — no full text of the sourcecites [22] Pathak JL, Yan Y, Zhang Q, et al. The role of oral microbiome in respiratory health and diseases. Respir med. 2021; 185: 106475. 34049183 source
• Not checked yetcites [39] Yu FY, Wang QQ, Li M, et al. Dysbiosis of saliva microbiome in patients with oral lichen planus. BMC Microbiol. 2020; 20: 75. 32245419 PMC7118920
• Supported

  In the Background section, the paper says the oral microbiome helps maintain oral health and associates oral microbiota dysbiosis with periodontal and systemic diseases. Its discussion of systemic diseases also states that oral microbiome community composition may be associated with periodontitis, cancer, and diabetes. This supports the claim as an association, not a causal assertion. (LLM, conf=0.93)

  cites [40] Huang C, Shi G. Smoking and microbiome in oral, airway, gut and some systemic diseases. J Transl Med. 2019; 17: 225. 31307469 PMC6632217 source
• Supported

  The Introduction (page not available) links oral bacteria to periodontitis and reports associations between periodontal disease and rheumatoid arthritis, while also noting a study that found no correlation. It reports altered oral flora in patients with Sjögren’s syndrome. Together, these passages support the broad association with oral and systemic health, without establishing that every oral condition is associated with systemic disease. (LLM, conf=0.86)

  cites [41] De Luca F, Shoenfeld Y. The microbiome in autoimmune diseases. Clin Exp Immunol. 2019; 195: 74– 85. 29920643 PMC6300652 source

In the paper

“Of the 450 patients with dental fluorosis, 290 were also affected by dental caries.”

In the paper

“together with reduced Streptococcus sanguinis, Rothia aeria, Fusobacterium periodonticum, Haemophilus, Gemella, Fusobacterium, Gemellaceae, Fusobacteriaceae, Pasteurellaceae, Lactobacillales, and Staphylococcales abundance relative to the HC group”

In the paper

“KO analysis showed a significant difference between the two groups, with most of the functional genes under-represented in the DF group.”

What the sources say

• Not checked yet

  Checked before — its earlier verdict is held back until a new check runs.

  cites [33] Douglas GM, Maffei VJ, Zaneveld JR, et al. Picrust2 for prediction of metagenome functions. Nat Biotechnol. 2020; 38: 685– 688. 32483366 PMC7365738 source

In the paper

“Here, significant decreases in the abundance of these species were observed in the DF group, consistent with a lower risk of future caries development.”

In the paper

“Function analyses showed increases in arginine biosynthesis in patients affected by dental fluorosis, together with reductions in amino sugar and nucleotide sugar metabolism, fructose and mannose metabolism, and starch and sucrose metabolism.”

In the paper

“Vibrio metschnikovii (V. metschnikovii) and Cupriavidus pauculus (C. pauculus) were dominant species that were more abundant in DF patients and able to discriminate between these patients and those in the HC group.”

In the paper

“Thus, the sample size was expanded from 178 to 957 to decrease the experimental error.”

In the paper

“Moreover, arginine is a promising agent for caries management [62].”

What the sources say

• ?Not checked — no full text of the sourcecites [62] Li J, Huang Z, Mei L, et al. Anti-caries effect of arginine-containing formulations in vivo: a systematic review and meta-analysis. Caries Res. 2015; 49: 606– 617. 26536588 source

In the paper

“Dean’s index was used to record the incidence and severity of dental fluorosis as follows: 0 (normal), 0.5 (questionable), 1 (very mild), 2 (mild), 3 (moderate), and 4 (severe) [24,25].”

What the sources say

• ?Not checked — no full text of the sourcecites [24] Zhou Y, Chen DR, Zhi QH, et al. The prevalence and associated risk indicators of dental fluorosis in china: findings from the 4th national oral health survey. Chin J Dent Res. 2018; 21: 205– 211. 30255171 source
• Not checked yet

  Checked before — its earlier verdict is held back until a new check runs.

  cites [25] Dong H, Yang X, Zhang S, et al. Associations of low level of fluoride exposure with dental fluorosis among U.S. children and adolescents, NHANES 2015-2016. Ecotoxicol Environ Saf. 2021; 221: 112439. 34166938 source

In the paper

“Arginine deiminase system (ADS)-positive bacteria can contribute to the alkalization of the oral microenvironment via arginine and proline metabolism, and can inhibit the growth of acidic cariogenic bacterial species such as S. mutans [61].”

What the sources say

• Not checked yet

  Checked before — its earlier verdict is held back until a new check runs.

  cites [61] Abranches J, Zeng L, Kajfasz JK, et al. Biology of Oral Streptococci. Microbiol Spectr. 2018; 6. DOI: 10.1128/microbiolspec.GPP3-0042-2018. PMC6287261 30338752 source

In the paper

“The necessary sample size for this study was calculated using the formula N=(Zα/2/δ)2P(1-P) in order to ensure that this study was adequately powered to assess dental fluorosis prevalence as per the results of the 4th National Oral Health Survey in China [24]. When the values of α, Zα/2, δ, and P were set as 0.05, 1.96, 5%, and 13.4%, the minimum sample size required for this study was calculated”

What the sources say

• ?Not checked — no full text of the sourcecites [24] Zhou Y, Chen DR, Zhi QH, et al. The prevalence and associated risk indicators of dental fluorosis in china: findings from the 4th national oral health survey. Chin J Dent Res. 2018; 21: 205– 211. 30255171 source

In the paper

“Zhong et al reported the microbial diversity in fecal samples from rat models of dental fluorosis, revealing an initial increase in such diversity (ACE and Chao indices) with rising NaF levels (25 or 50 mg/L for 12 weeks), whereas this diversity fell when higher levels of NaF were provided in the water given to these rats (100 and 150 mg/L groups) [21].”

What the sources say

• ?Not checked — no full text of the sourcecites [21] Zhong N, Ma Y, Meng X, et al. Effect of fluoride in drinking water on fecal microbial community in rats. Biol Trace Elem Res. 2022; 200: 238– 246. 33576944 source

In the paper

“Although it is a micronutrient required for normal growth, excessive long-term fluoride intake can lead to its deposition in the bones and teeth, resulting in chronic skeletal and dental fluorosis [2,3].”

What the sources say

• Not checked yet

  Checked before — its earlier verdict is held back until a new check runs.

  cites [2] Li Q, Shen J, Qin T, et al. A qualitative and comprehensive analysis of caries susceptibility for dental fluorosis patients. Antibiotics (Basel). 2021; 10: 1047. 34572628 PMC8464924 source
• Not checked yet

  Checked before — its earlier verdict is held back until a new check runs.

  cites [3] Qiao L, Liu X, He Y, et al. Progress of signaling pathways, stress pathways and epigenetics in the pathogenesis of skeletal fluorosis. Int J Mol Sci. 2021; 22: 11932. 34769367 PMC8584317 source

In the paper

“C. pauculus is a non-fermentative, aerobic bacillus that is relatively rare”

What the sources say

• Not checked yet

  Checked before — its earlier verdict is held back until a new check runs.

  cites [51] Huda SA, Yadava S, Kahlown S, et al. A rare case of ventilator-associated pneumonia caused by Cupriavidus Pauculus. Cureus. 2020; 12: e8573. 32670709 PMC7358901 source
• Not checked yet

  Checked before — its earlier verdict is held back until a new check runs.

  cites [52] Almasy E, Szederjesi J, Rad P, et al. A fatal case of community acquired Cupriavidus Pauculus Pneumonia. J Crit Care Med (Targu Mures). 2016; 2: 201– 204. 29967861 PMC5953259 source
• Not checked yet

  Checked before — its earlier verdict is held back until a new check runs.

  cites [53] Yahya R, Alyousef W, Omara A, et al. First case of pneumonia caused by Cupriavidus pauculus in an infant in the gulf cooperation council. J Infect Dev Ctries. 2017; 11: 196– 198. 28248683 source
• Not checked yet

  Checked before — its earlier verdict is held back until a new check runs.

  cites [54] Wallet F, Tachon M, Nseir S, et al. Vibrio metschnikovii pneumonia. Emerg Infect Dis. 2005; 11: 1641– 1642. 16355507 PMC3366744 source

In the paper

“While exposure to a 100 mg/L dose of fluoride does not impact the diversity of the rat fecal microbiome, the richness of these intestinal communities initially rises and then falls as the levels of fluoride in the water rise [21].”

What the sources say

• ?Not checked — no full text of the sourcecites [21] Zhong N, Ma Y, Meng X, et al. Effect of fluoride in drinking water on fecal microbial community in rats. Biol Trace Elem Res. 2022; 200: 238– 246. 33576944 source

In the paper

“Dental fluorosis results from the intake of excessively high fluoride levels through water, soil, brick tea, and coal-based sources via the digestive or respiratory tract, in turn impacting ameloblast development and altering the morphology and mechanical properties of teeth [9].”

What the sources say

• ?Not checked — no full text of the sourcecites [9] Li Q, Zhao ZJ. Prevalence of brick tea-type fluorosis in children aged 8-12 years in Qinghai Province, China. Biomed Environ Sci. 2021; 34: 334– 336. 33894815 source

In the paper

“Jing et al reported that AhrC is also an important transcription factor that negatively regulates arginine biosynthesis gene expression and biofilm formation in S. mutans [65].”

What the sources say

• Not checked yet

  Checked before — its earlier verdict is held back until a new check runs.

  cites [65] Jing M, Zheng T, Gong T, et al. AhrC negatively regulates Streptococcus mutans arginine biosynthesis. Microbiol Spectr. 2022; 10: e0072122. 35938859 PMC9430756 source

In the paper

“Streptococcus mutans (S. mutans) is the bacterium largely responsible for caries formation [42].”

What the sources say

• Not checked yetcites [42] Loesche WJ. Role of Streptococcus mutans in human dental decay. Microbiol Rev. 1986; 50: 353– 380. 3540569 PMC373078

In the paper

“These pathways are associated with active carbohydrate metabolism in the context of cariogenesis [58–60].”

What the sources say

• ?Not checked — no full text of the sourcecites [58] Dashper SG, Reynolds EC. Lactic acid excretion by Streptococcus mutans. Microbiology (Reading). 1996; 142: 33– 39. 33657745 source
• ?Not checked — no full text of the sourcecites [59] Zeng L, Chakraborty B, Farivar T, et al. Coordinated regulation of the EII(Man) and fruRKI Operons of Streptococcus mutans by global and fructose-specific pathways. Appl Environ Microbiol. 2017; 83. DOI: 10.1128/AEM.01403-17 PMC5648919 28821551 source
• Not checked yetcites [60] Klein MI, DeBaz L, Agidi S, et al. Dynamics of Streptococcus mutans transcriptome in response to starch and sucrose during biofilm development. PLoS ONE. 2010; 5: e13478. 20976057 PMC2957427 source

In the paper

“Several studies showed that Streptococcus sanguinis (S. sanguinis) may play an antagonistic role against S. mutans colonization and is usually associated with tooth surfaces free of caries [43–45].”

What the sources say

• Not checked yet

  Checked before — its earlier verdict is held back until a new check runs.

  cites [43] Becker MR, Paster BJ, Leys EJ, et al. Molecular analysis of bacterial species associated with childhood caries. J Clin Microbiol. 2002; 40: 1001– 1009. 11880430 PMC120252 source
• ?Not checked — no full text of the sourcecites [44] Marchant S, Brailsford SR, Twomey AC, et al. The predominant microflora of nursing caries lesions. Caries Res. 2001; 35: 397– 406. 11799279 source
• ?Not checked — no full text of the sourcecites [45] Giacaman RA, Torres S, Gomez Y, et al. Correlation of Streptococcus mutans and Streptococcus sanguinis colonization and ex vivo hydrogen peroxide production in carious lesion-free and high caries adults. Arch Oral Biol. 2015; 60: 154– 159. 25455129 source

In the paper

“High fluoride doses can lead to DNA damage, mitochondrial damage, endoplasmic reticulum (ER) stress, and apoptotic death, thereby impairing ameloblast function and disrupting the normal synthesis and secretion of enamel-associated proteins via the impairment of normal ER function [10–13].”

What the sources say

• ?Not checked — no full text of the sourcecites [10] Liu X, Huang R, Gao Y, et al. Calcium mitigates fluoride-induced kallikrein 4 inhibition via PERK/eIf2alpha/ATF4/CHOP endoplasmic reticulum stress pathway in ameloblast-lineage cells. Arch Oral Biol. 2021; 125: 105093. 33667956 source
• ?Not checked — no full text of the sourcecites [11] Zhou X, Chen Z, Zhong W, et al. Effect of fluoride on PERK-Nrf2 signaling pathway in mouse ameloblasts. Hum Exp Toxicol. 2019; 38: 833– 845. 30977402 source
• Not checked yet

  Checked before — its earlier verdict is held back until a new check runs.

  cites [12] Aulestia FJ, Groeling J, Bomfim GHS, et al. Fluoride exposure alters Ca(2+) signaling and mitochondrial function in enamel cells. Sci Signal. 2020; 13. DOI: 10.1126/scisignal.aay0086. PMC7173621 32071168 source
• Not checked yet

  Checked before — its earlier verdict is held back until a new check runs.

  cites [13] Suzuki M, Bandoski C, Bartlett JD. Fluoride induces oxidative damage and SIRT1/autophagy through ROS-mediated JNK signaling. Free Radic Biol Med. 2015; 89: 369– 378. 26431905 PMC4684823 source

In the paper

“which makes periodontal bacteria easier to colonize on the tooth surface and difficult for scaling and root planning”

What the sources say

• Not checked yet

  Checked before — its earlier verdict is held back until a new check runs.

  cites [49] Singh P, Gupta ND, Bey A. Dental fluorosis and periodontium: a game of shadows? J Oral Biol Craniofac Res. 2014; 4: 47– 48. 25737919 PMC4252631 source

In the paper

“Vandana et al reported that there is a strong association of occurrence of periodontal disease and dental fluorosis [48].”

What the sources say

• Not checked yet

  Checked before — its earlier verdict is held back until a new check runs.

  cites [48] Vandana KL, Reddy MS. Assessment of periodontal status in dental fluorosis subjects using community periodontal index of treatment needs. Indian J Dent Res. 2007; 18: 67– 71. 17502711 source

In the paper

“For these 200 patients, exclusion criteria included the presence of dental caries, recurrent oral ulcers, periodontitis, other oral diseases, systemic or genetic diseases, or the use of any antibiotics, tobacco, and probiotics within the past six months.”

In the paper

“Many studies have explored the association between gender and salivary microbiome, and reported that there was gender-specific difference in the salivary microbiome [56,57].”

What the sources say

• Not checked yet

  Checked before — its earlier verdict is held back until a new check runs.

  cites [56] Ortiz S, Herrman E, Lyashenko C, et al. Sex-specific differences in the salivary microbiome of caries-active children. J Oral Microbiol. 2019; 11: 1653124. 31497256 PMC6720314 source
• Not checked yet

  Checked before — its earlier verdict is held back until a new check runs.

  cites [57] Nearing JT, DeClercq V, Van Limbergen J, et al. Assessing the variation within the oral microbiome of healthy adults. mSphere. 2020; 5. DOI: 10.1128/mSphere.00451-20 PMC7529435 32999079 source

In the paper

“the dysbiosis of this microbial community has been linked to diseases of the oral cavity (dental caries, gingivitis, periodontitis, oral lichen planus, oral cancer), respiratory system (pneumonia, asthma, chronic obstructive pulmonary disease, lung cancer), gastrointestinal system (Crohn’s disease, ulcerative colitis, colonic carcinoma), and other systems [22,39–41].”

What the sources say

• ?Not checked — no full text of the sourcecites [22] Pathak JL, Yan Y, Zhang Q, et al. The role of oral microbiome in respiratory health and diseases. Respir med. 2021; 185: 106475. 34049183 source
• Not checked yetcites [39] Yu FY, Wang QQ, Li M, et al. Dysbiosis of saliva microbiome in patients with oral lichen planus. BMC Microbiol. 2020; 20: 75. 32245419 PMC7118920
• Not checked yet

  Checked before — its earlier verdict is held back until a new check runs.

  cites [40] Huang C, Shi G. Smoking and microbiome in oral, airway, gut and some systemic diseases. J Transl Med. 2019; 17: 225. 31307469 PMC6632217 source
• Not checked yetcites [41] De Luca F, Shoenfeld Y. The microbiome in autoimmune diseases. Clin Exp Immunol. 2019; 195: 74– 85. 29920643 PMC6300652 source

In the paper

“Hu et al. found that tooth biofilm formation in individuals with moderate to severe dental fluorosis (Dean index = 3–4) was associated with differences in S. mutans adherence relative to the ability of these microbes to bind the surface of sound enamel [47].”

What the sources say

• ?Not checked — no full text of the sourcecites [47] Hu D, Gong J, He B, et al. Surface properties and Streptococcus mutans - Streptococcus sanguinis adhesion of fluorotic enamel. Arch Oral Biol. 2021; 121: 104970. 33202357 source

In the paper

“For example, the intake of elevated fluoride levels (80 mg/L) can alter both the makeup and diversity of the gut microbiota in common carp, resulting in reduced Actinobacteria abundance with a concomitant increase in Firmicutes and Fusobacterium abundance [20].”

What the sources say

• ?Not checked — no full text of the sourcecites [20] Yu H, Zhang Y, Zhang P, et al. Effects of fluorine on intestinal structural integrity and microbiota composition of common carp. Biol Trace Elem Res. 2021; 199: 3489– 3496. 33119815 source