A related post, trimethylamine oxide, makes a case for oral microbiome transplantation. In the case of TMA, which gets converted to TMAO largely by the liver, it is really hard to argue that the production of TMA by the oral microbiome can come close to the production by the fecal microbiome.
OMT studies
Li 2022 review [1]
The Li 2022 review is all about justifying OMT for the treatment of cardiovascular disease.
- The beneficial aspect of effects of SCFA on energy metabolism and as anti-inflammatory agents was discussed. The obvious other edge of this “double edged sword” is local solidification.
- The benefits of nitrite as of vasorelaxant nitric oxide were discussed as were bacteria that may reduce nitrate to nitrite. [5] Only a brief mention was given to post translational thiol nitosylation.
- Sulfate reduction to hydrogen sulfide, H2S was also discussed. The review did not make a convincing case for the oral micro biome producing enough H2S to make a systemic difference
- TMAO… was also discussed. but not that well. Is enough TMA produced to make its way to the liver? Is there enough FMO3 to convert to TMA to TMAO?
In a way Li et al made a poor case for OMT for cardiovascular disease based on these metabolic biproducts but a good case for OMT for the mouth-brain axis issues. Not all bacteria can reduce nitrate and sulfate. Not all bacteria can convert choline to TMA.
Tongue coating microbiota [2]
Much of this review concentrated on the hypothesis that nitrate reducing bacteria on the tongue contribute significantly to overall cardiovascular health by increasing ntiric oxide concenttrations. Here is one
What does a taste receptor look like? Is this a route for nitrite, nitrosothiols, NO2, or whatever to enter the circulation? The tastebuds are actually within three of the four types of lingual papillae on the human tongue: circumvallate (or vallate), fungiform, filiform, and foliate. The filiform papillae are not associated with tastebuds.
Can microorganisms enter the actual taste bud? Saliva glands are a subset of serious glands. Can oral bacteria have a direct route to the brain via innervation of the oral cavity?
In this review Li and coauthors made the remark, “In traditional Chinese medicine, the relationship between the five tastes and the internal organs was proposed as early as the period of the Inner Canon of the Yellow Emperor: sour taste enters the liver, astringent taste enters the lung, and bitter taste enters the heart. These observations have been clinically corroborated in long-term clinical practice”
Antimicrobial Peptides [3]
Is the saliva of dog or rodent the same of that of a human? Years ago I attended a seminar on anti-microbial peptides in saliva, dogs in particular. The speaker referenced a story about a poor beggar named Lazarus whose open sores were licked by dogs while a rich man partied on. Dogs and cats wear “cone’s of shame” to prevent them from licking open wounds after surgeries. How much of this is to prevent them from opening the stitches or to prevent infection of the wound with the oral microbiome? Do dogs, cats, and rodents have a more aerotolerant microbiome than humans since they seem to have their mouths open more?
In this mouse study the major saliva producers, submandibular gland (SMG) and/or sublingual gland (SLG), were removed. Components of these secretions include antimicrobial proteins as well as other components.
This relates to the 2022 Li review [1] claiming that H2S production in the oral cavity can benefit hypertension. Desulfovibrio is an obligate anaerobe and sulfate reducer. Li and coauthors stated that H2S is toxic to collagen. Collagen and other extracellular matrix proteins are cross-linked by disulfide bonds. H2S can reduce these disulfide bonds. Oral Streptococcus production of trimethylamine was discussed in the trimethylamine oxide post. Burkholderia is a biofilm former and usually pathogenic.
Proteins
There seems to be some typos in these figures that the reviewers missed. Here are some comments on these proteins:
- Prolactin-inducible protein (PIP) has an immunoglobulin fold-like structure that contributes to the aggregation of oral bacteria. Aggregation is thought to promote the clearance of bacteria from the oral cavity and can influence the composition of the oral bacterial community. Lactoperoxidase (LPO), a member of the salivary peroxidase system, exerts a broad-spectrum bactericidal effect (Morita et al., 2017).
- CTSD (cathepsin D) is a protease
- CD44 (CD44 antigen),
- COL1A2 (collagen alpha-2) is an extracellular matrix protein.
- SCGB2B26, SCGB1B27, and SCGB2B27 are members of the Secretoglobin superfamily.
- salivary mucin, MUC19 lubricates and protects oral surfaces
- Ovostatin homolog (OVOS) was belong to the immunoglobulin E set.
- a non-secreted protein, the polymeric immunoglobulin receptor (PIGR), has been reported to be positively correlated with IgA concentrations in mouse saliva .
“Meanwhile, SCGB2B26, SCGB1B27, SCGB2B27, and OVOS are involved in acquired immunity, which also effects the oral microflora. SCGB2B26, SCGB1B27, and SCGB2B27 were more abundant in the SMG. These secretoglobins play an important role in maintaining microbial homeostasis by binding to surface molecules of pathogenic microorganisms, such as adhesins, preventing them from adhering to the oral mucosa”
Let’s take the mouse anti-microbial peptide gene, Scgb2b26, and do a a protein blast of the human geneome. No matches were found. Moving forward, a study used mass spectrometry to compare the saliva proteome of seven Thai sciencetists with seven village dogs in an effort to understand why canine saliva has superior antimicrobial properties. [4] considerable differences were found that seemed to have little to do with officially recognized anti-microbial peptides. [4] The mouse/rat saliva proteomes were found to be different from the human. [5] Probably the next consideration is what, if anything, can lead to variability in the human saliva proteome? We know from the study of Li 2023 that saliva proteins influence the rat oral microbiome. [3]This has implications in the human condition even if our proteomes are different.
References
- Luo B, Cui J, Huang L, Chen K, Liu Y. The oral microbiota and cardiometabolic health: A comprehensive review and emerging insights. Front Immunol. 2022 Nov 18;13:1010368. PMC free article
- Li Y, Cui J, Liu Y, Chen K, Huang L, Liu Y. Oral, Tongue-Coating Microbiota, and Metabolic Disorders: A Novel Area of Interactive Research. Front Cardiovasc Med. 2021 Aug 20;8:730203. PMC free article
- Li Y, Liu J, Guan T, Zhang Y, Cheng Q, Liu H, Liu C, Luo W, Chen H, Chen L, Zhao T. The submandibular and sublingual glands maintain oral microbial homeostasis through multiple antimicrobial proteins. Front Cell Infect Microbiol. 2023 Jan 10;12:1057327. PMC free article
- Sanguansermsri P, Jenkinson HF, Thanasak J, Chairatvit K, Roytrakul S, Kittisenachai S, Puengsurin D, Surarit R. Comparative proteomic study of dog and human saliva. PLoS One. 2018 Dec 4;13(12):e0208317. PMC free table
- Karn RC, Chung AG, Laukaitis CM. Shared and unique proteins in human, mouse and rat saliva proteomes: Footprints of functional adaptation. Proteomes. 2013 Dec 1;1(3):275-289. PMC free article
