The role of Salivary IgA in Oral microbial Ecology

[halitosisux]

Phantasist,
while I believe that its always a possibility that some missing component in saliva could be the cause of excessive bacterial activity in the mouth, I have tried to balance the argument with why I also believe that this isnt the case - which as you know, I've detailed in other threads.

Most of all, I think a direct comparison between the saliva of those with and those without BB would reveal the differences.

Remember also, what aydinmur said, that babies never have BB. If there was a genetically determined "fault" with saliva, leading to BB, then surely this would become apparent at this early stage in life, where, according to Aydinmur, a baby's developed microbial flora once its been exposed to the outside world is almost the same as an adult's flora.

I realise how important saliva is for keeping a healthy ecology in the mouth, in terms of basics such as saliva quantity, flow and its role in maintaining the oral pH, so saliva must never be overlooked as a cause of BB if problems such as dry mouth are present, as they often are.

[sadman]

Hali :

while I believe that its always a possibility that some missing component in saliva could be the cause of excessive bacterial activity in the mouth, I have tried to balance the argument with why I also believe that this isnt the case - which as you know, I've detailed in other threads.

This is what I found out :

The underlying immunoligical host mechanisms if
compromised, may contribute to the imbalance in the
oral microflora and these mechanisms need to be
explored. Immunoglobulin A is one of the factors that
maintains the balance of oral microflora and contributes
to the resistance of oral infections. Bacterial enzymes
interfere with IgA defense mechanisms and may compromise
host immunity by a variety of methods. Although
selective IgA deficiency is hereditary in 0.1% of the population,
there is evidence that IgA deficiency can be
acquired. Further, it has been established that stress
impairs immunologic functioning and a stressed individual
is more likely to develop an unhealthy condition. Further
exploration of this concept may establish a definite link
between a compromised immune system and oral ma~
odour. Treatment could then be aimed at controlling the
secondary immune dysfunctions as well as eliminating
the microbial infection. The end result would be more
effective and long lasting.

Hali :

Remember also, what aydinmur said, that babies never have BB

Babies do have bad breath :

[halitosisux]

Yes, agreed. This has been talked about before - Which is why everyone needs to ensure that they have the relevant tests to rule this out.

One particular disorder of the immune system which I've never seen mentioned
is Chronic mucocutaneous candidiasis.
http://en.wikipedia.org/wiki/Chronic_mu ... andidiasis

We keep hearing about candida and candida diets etc, and many have now tried antifungal drugs and have proved that an opportunistic infection of candidiasis is not the cause of their BB.

So something like this or any other immune deficiency could be the simple answer for some.

Regarding babies, I've never come across one with BB. Yet about half of the adults I come across have got some degree of bad breath (excluding 'therabreath' odours like coffee, I'm talking proper bad breath)

BTW I can remember one baby that smelled yeasty, not a foul smell, but almost identical to the smell of yeast you'd use to make bread with.

Also, the very worst cases of odour that originate in the mouth do not travel more than 2 or 3 feet. Anything that travels further is probably relating to different gases which tend to linger, originating from other areas such as the lungs, as occurs with bloodborne odours such as TMAU.

[Phantasist]

What Sadman is telling us, is exactly what I have suspected. Namely that there is a component in "normal" people's saliva that provides an immunity against the overgrowth of anaerobic bacteria. It could well be the Salivary Immunoglobulin A (SIgA). It follows then that if there is a deficiency of SIgA, that there would be no natural defense against the bad bacteria taking over the oral ecology.
It also appears that this deficiency of Salivary IgA can be inherited, which would make it genetic. Maybe it can also be acquired, but at this point I don't really understand how that could happen.
Sadman's explanation would make perfect sense, because it would explain everything we have been puzzling about this particular type of bad breath (where no APPARENT cause, such as infected teeth, tonsils, sinuses or lung, stomach, colon problems, etc..... are in evidence).

[halitosisux]

Phantasist, It will make even more sense when you go and have tests for it.
IgA deficiency/disorder, as well as other immunological disorders usually results in having certain kinds of repeated infections. A doctor will tend to suspect this and refer for tests, leading to a diagnosis.

[aydinmur]

Friends ,
I read your messages since 1 week. I admire your great effort. Congratulations. I wish my all patients can be so well informed like you.

This is too complex matter. IgA level restricts some bacteria but not all.
IgA is not unique key of oral immun status.

There are phosphoproteins in parotid saliva. Acidic-Proline-Riched-Protein (PRP) and statherin. Called "histatin". Found ~25 ug/mg saliva. This covers oral surfaces like a layer. Protects tissues from bacterial attack, decreases trigger level of mast cells, histiocytes, makes Th cells sensitive to interleukin -1beta. Histatin is nonspecific, defence layer. 10000 molecules of PRP stick on 1 um^2 tooth surface. It also neutralize lipid A that comes from Gram negatif bacterial membranes. This layer is friend of oral tissues.

Do you want to my tell you more ?

Ok.
Actinomyces members secret neurominidase like enzymes. These enzymes are secreted by bacteria, they snip the histatin layer. Once snipped the protein fibrilar network, then hook molecules appear within histatin layer on oral surfaces. Note that there is not IgA here.

There are more than one enzyme that is able to cut histatin layer. They are secreted by oral bacteria, or syntezied by them. Here there are surprises. Unfortunately some cytokines by our immun cells my cut statherin layer like bacterial neurominidases.

Eventually thousands hook molecules per mm^2 of oral surface appear. Bacteria catch these hooks with their mannose sensitive fimbirae. In result, More bacteria is more halitosis.

Dont make zoom on IgA.
This is too complex matter than you think.

Hope helps
-Murat

[Phantasist]

Murat Aydin,
First of all, thank you once again for your input. You have given us a tremendous amount of information, and we can see without a doubt how devilishly complicated this problem is. This is the reason why those of us who suffer from this type of BB are never helped by doctors or dentists. We have read that there are many different species of bacteria in the mouth, and that there are many different components in the saliva. We don't know the effect of each one, so it is almost impossible to unravel this puzzle.
But I still have a sneaking suspicion that something in a healthy person's saliva keeps the anaerobic bacteria in check. We may not know what it is, or how it interacts. But if this were the case, all the pieces of the puzzle would fall into place. Maybe I'm looking for a too simple solution, but there seems to be some circumstantial evidence that it has something to do with the saliva.
For instance: Even people who normally don't have bad breath, sometimes have "morning breath". This must be due to the diminished saliva production during sleep when the anaerobic bacteria multiply. But after these people get up, normal saliva production resumes, and after 15 or 20 minutes, their morning breath disappears. Just one bit of evidence.

[aydinmur]

Dear Phantasist,
Morning breath is not only type 1 halitosis. But it consists of Type 1+2+3+4 halitosis. Dont restrict your thinks with oral reasons.

By the way, did you know, even cats, dogs other mammalians have morning breath.

- Murat Aydin

[Phantasist]

Aydin Murat,
I didn't imply that "morning breath" is a disease. I simply said that it must have something to do with the reduction in saliva flow during sleep. Are you telling us that it has nothing to do with that?

Thank you for telling us that there are other components in saliva besides IgA (PRP and Statherin) that put down a protective layer on oral surfaces and that there are also bacteria that can create enzymes that can cut through the protection. What you are describing is a bacteriological battle going on in our mouths. This makes it a little more complicated, but unless I am wrong, it doesn't rule out the idea that the saliva is the important factor.

Don't forget that we are not microbiologists and don't have the knowledge that you have. The only tools that I have at my disposal to find an answer are logic, observation, some circumstantial evidence and trial-and-error. I'm fully aware that these means are probably not equal to the task to unravel this complicated problem. We are all trying our best here to find an answer, but I will probably give up soon.

[Phantasist]

Halitosisux,
You seem to place a lot of faith in doctors. I'm sure you know that most of us in this forum have been to doctors and dentists for many years, and the reason why we are here is because the doctors and dentists didn't help us.

[sadman]

We all know that there are many components of the Saliva that have antimicrobial property such as IgA , IgM, Lactoferrin, Lactoperoxidase , Lysozyme , Mucins, Proline , Statherin, Histatin , not to mention Beta-defensin which is produced by the epithelial cells of the oral mucosa and has a wide spectrum , acting on Gram negative and positive bacteria . What I emphasized here is that most of halitosis cases happened not at birth but at sometime in life , so it must be something to do with an acquired deficiency of those components . There is literature relating acquired deficiency of SIgA ( which is caused by a disorder of B-lymphocytes : http://webcache.googleusercontent.com/s ... =firefox-a ) with Halotosis but I can not find any literature about other component's acquired deficiency except a report of low Histatin level in AIDS patients which predispose this population to oral Candidiasis since the most significant function of Histatin is its anti-fungal activity , but again this low level of Histatin happens in an immunocompromised patients :

http://onlinelibrary.wiley.com/doi/10.1 ... x/abstract

As Halitosisux already mentioned , a direct comparison between the Saliva of those with and without BB would reveal the differences

[halitosisux]

Phantasist,
I dont place a lot of faith in doctors actually, particularly dentists, neither of which in over two decades of battling helped to guide me in the slightest. So I do know what people are going through on this forum, and that's why I am trying to help.

[Phantasist]

Yes, a detailed comparison of the components in the saliva of two groups of BB-positive and BB-negative subjects should show the difference, but has such a comparison ever been made? It occurs to me that this would not be a very urgent area of research.
It's all very well for Halitosisux to say, go to a doctor and have him send you for the tests, but we all know how far that would get me.
1) He would think that I was nuts, and try to talk me out of it.
2) He wouldn't know anything about it, because the average doctor is not a microbiologist who has done studies on BB.
3) Even if he had my saliva tested, he wouldn't know how to evaluate the results, and he would have nothing to compare them to.

You might guess that my past experiences with doctors were not fruitful.

[halitosisux]

Phantasist, having immunological testing/ full blood count etc is part of standard blood testing as far as I know - and if its not, I cant imagine it being all that difficult to convince a doctor to try out a few variations, armed with a few printouts etc.

Most of my dealings with doctors involved indirect approaches to get what I wanted.

[sadman]

FYI:

http://webcache.googleusercontent.com/s ... =firefox-a

http://ukpmc.ac.uk/articles/PMC2094851; ... 3EA85.jvm1

http://webcache.googleusercontent.com/s ... =firefox-a


Saliva contains naturally potent anticandidal proteins called histatins.15,16 These are believed to help control oral flora and are reported to be reduced in AIDS-immunosuppressed patients,17 thus rendering the individuals susceptible to mucosal candidiasis. This is particularly dangerous if Candida species develop that are resistant to common azole-type, oral antifungal drugs (e.g., fluconazole). The authors reasoned that if they could increase the production of histatins in such patients by gene transfer to the salivary glands, they could prevent or eliminate such infections. Although the specific mechanism of action by which histatins kill Candida is not yet clearly known, it appears to be different from that of azole drugs. Therefore, histatins may be effective against azole-resistant Candida species. Furthermore, the authors reasoned, it would not be necessary for the gene transfer to be permanent. Rather, it seemed likely that a "therapeutic" course of gene expression (10 to 14 days) would be adequate for this purpose. This meant that the authors could probably employ the current generation of adenoviruses as a gene transfer vector.10

They constructed a recombinant adenovirus encoding histatin 3,18 one of the histatin protein family members with demonstrated anticandidal action.16,17 They showed that this virus was able to direct the expression of authentic histatin 3 in a cell culture model and, more importantly, lead to the secretion of histatin 3 in rat saliva after infection of rat salivary glands with the vector. This is particularly noteworthy since rats do not normally make histatin 3. Further, the levels of histatin 3 found in rat saliva were as high as ~1.5 mg/ml, more than tenfold that seen normally in humans.18 Of greatest significance, recombinant histatin 3 was able to kill azole-resistant Candida in vitro.18 The authors are now engaged in a preclinical series of experiments, using immunosuppressed rabbits, to determine if this virus, and the researchers' approach, will be useful under more therapeutic conditions. If these studies are successful, the authors expect to be able to apply this gene transfer treatment to patients within a reasonable time.

The authors have also begun to test various strategies to augment saliva with proteins that could disrupt or limit dental plaque formation.19 Although this has not yet provided the positive results seen with the anti-Candidal strategy described above, they believe it shows considerable promise conceptually. The value of limiting dental plaque to prevent dental disease has been long recognized and is widely applied with conventional pharmacotherapeutics.20 Thus far, these conventional approaches have been only partially successful. A gene transfer approach likely would be entirely complementary to conventional methods and may substantially increase the extent to which dental plaque can be diminished. The authors expect that this approach, or another not yet conceived, will be able one day to reduce dental plaque formation substantially and eliminate caries and periodontal disease.

http://webcache.googleusercontent.com/s ... =firefox-a