Biomarkers for navigating autoimmune health challenges - DAO, LPS and Zonulin

3 Bio-markers are Potential Game Changers for Autoimmune Sufferers

This year has already flown by, I can’t believe we are in the third month already! I have many things in the works to share with you and have been eager for reliable internet service to share these fascinating diagnostic testing options with you.  Especially for those on that auto-immunity journey and those on that health journey roller coaster which seems to have wheels spinning in circles…

I’ll cut to the chase – DAO, LPS and Zonulin – Have you heard of them?  Do you know their significance?  Let me give a brief, and I mean brief, overview of what they are and why they are significant.

What are they?

DAO – Diamine Oxidase is primarily secreted in the digestive tract and helps set the stage for a healthy environment in the digestive tract.   Do you have any guesses as to one of the things which happens when someone has low DAO?  If you guessed an adverse environment with an unhealthy microbiome you guessed correct!

LPS – Lipopolysaccharide is also primarily located in the gut.  It is an endotoxin which comes about as your body is fighting bacteria. When we find this in the blood that tells us it is no longer confined in the digestive tract, rather has made its way into our system!

Zonulin – (this is one you may have heard about!) Dr. Alessio Fasano, from Italy, is responsible for discovering the role of this fascinating protein.  Simply put – Zonulin is responsible for opening the tight junctions thereby allowing ‘stuff’ to pass between the cells lining the digestive tract. (If you want to dig deeper and connect some dots on your health journey take a minute and do a quick search at Pubmed: “Fasano Zonulin” and see what turns up 🙂

zonulin illustration

What is the significance?

First, if you haven’t read about the microbiome you may want to check out this post. When our digestive tract has an unhealthy environment that sets the stage for unhealthy flora to take up residence.  In addition what is typically healthy flora can get out of balance and become overpopulated, thereby rendering this once helpful bacteria unhelpful.  Furthermore, this loops back to causing an imbalance so we are left with having an imbalance due to bad environment and a bad environment due to an imbalance – quite the ‘catch 22’ situation!

Next have you heard of antibodies?  Are you familiar with how they come about?  Again, a brief snapshot.  Antibodies are part of the second line of defense in our immune system.  SIgA is the first line involved in the elimination of ‘invaders’.  When these invaders make their way through the lining of the digestive tract(such as when Zonulin opens the door) antibodies come into the scene.  Can you see where this is headed and how this is tied to autoimmunity?

So, we have antibodies getting made and foreign invaders attaching to things where they shouldn’t and our body decides to do what it can to eliminate the offender despite the collateral damage!  It is rather fascinating how we are made!

In addition to all of this histamines and allergies come on the scene…  I said I was going to keep this brief so will leave it at that… Things start to go downhill and the circling domino effect magnifies… Autoimmunity takes hold…

zonulin related disease illustration

What can we do about abnormal findings?

Ah, the million dollar question!!!  I wish I had the answer you are looking for, the fact is there isn’t a one size fits all solution.  This is why those of us with autoimmune conditions often find ourselves spinning in circles trying this protocol and that protocol.  For instance, overall those with MS find Wahls protocol effective, others may find Autoimmune Paleo effective or perhaps SCD(Specific Carbohydrate Diet).  Some may need to tweak and eliminate FodMAPs, Histamines or Nightshades…

We find relief in one area and think we are on the road to healing then have another ‘episode’. What you do for your T1 Diabetic condition may be different than what needs to happen for my T1D son.  This is where these three tests can be very valuable! We know ‘leaky gut’ is associated with autoimmune diseases, so the challenge is to find the breach and fix it.  Is it due to low DAO?  Perhaps its an abundance of Zonulin?  What about a combination of the two?  This is where partnering with a functional practitioner is invaluable. We can help you identify patterns and nuances specific to your situation.   We have to look at all the clues given us, these three markers are just three of the many clues to your ‘health mystery’.

I would love to be able to tell you to take this probiotic, that combination of supplements and you go on your happy way to healing. But, one thing I am 10,000% certain of is we are individuals and a restoration of health must be customized!   Are there similarities and common components to the solutions?  Absolutely!!!

So, can I help you?  Most likely, but it would take looking at your health journey with a fine tooth comb! In the meantime I can recommend a few things which will encourage your body to seek homeostasis:

  • Lifestyle changes which support synchrony with circadian rhythms
  • Plenty of water
  • Real foods
  • Elimination of stress
  • Quality rest
  • Exercise
  • Laughter

The simplest way to come up with a customized plan will take one of two things:

Find a functional practitioner who is passionate about YOUR health challenges. (For instance my  primary interest is in autoimmune challenges, another practitioner may focus on cardiovascular or hormone challenges)  Many do not ‘specialize’ and that is ok, they can still help you formulate a plan!

or

Enroll in functional medicine training and put the pieces of your health back together.

Feel free to contact me with any questions or comments 🙂 And of course you can also take advantage of my free 15 min consult! Best wishes on your journey!

A few references:

Polyamine Oxidase and Diamine Oxidase Activities in Human Milk during the First Month of Lactation.
Bjelakovic L, Kocic G, Bjelakovic B, Najman S, Stojanović D, Jonovic M, Pop-Trajkovic Z.
Iran J Pediatr. 2012 Jun;22(2):218-22.
PMID: 23056889 Free PMC Article

https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3446060/

 

Zonulin, a regulator of epithelial and endothelial barrier functions, and its involvement in chronic inflammatory diseases.
Sturgeon C, Fasano A.
Tissue Barriers. 2016 Oct 21;4(4):e1251384. doi: 10.1080/21688370.2016.1251384. Review.
PMID: 28123927

http://www.tandfonline.com/doi/abs/10.1080/21688370.2016.1251384?journalCode=ktib20

 

Abnormal intestinal permeability and microbiota in patients with autoimmune hepatitis.
Lin R, Zhou L, Zhang J, Wang B.
Int J Clin Exp Pathol. 2015 May 1;8(5):5153-60.
PMID: 26191211 Free PMC Article

https://www.ncbi.nlm.nih.gov/pubmed/26191211

 

Chronic Kidney Disease Induced Intestinal Mucosal Barrier Damage Associated with Intestinal Oxidative Stress Injury.
Yu C, Wang Z, Tan S, Wang Q, Zhou C, Kang X, Zhao S, Liu S, Fu H, Yu Z, Peng A.
Gastroenterol Res Pract. 2016;2016:6720575. doi: 10.1155/2016/6720575.
PMID: 27493661 Free PMC Article

https://dx.doi.org/10.1155/2016/6720575

 

Concomitant Prevalence of Low Serum Diamine Oxidase Activity and Carbohydrate Malabsorption.
Enko D, Meinitzer A, Mangge H, Kriegshäuser G, Halwachs-Baumann G, Reininghaus EZ, Bengesser SA, Schnedl WJ.
Can J Gastroenterol Hepatol. 2016;2016:4893501. doi: 10.1155/2016/4893501.
PMID: 28042564 Free PMC Article

https://www.hindawi.com/journals/cjgh/2016/4893501/

 

Lipopolysaccharide-Induced Middle Ear Inflammation Disrupts the cochlear Intra-Strial Fluid–Blood Barrier through Down-Regulation of Tight Junction Proteins
Jinhui Zhang, Songlin Chen, Zhiqiang Hou, Jing Cai, Mingmin Dong, Xiaorui Shi
PLoS One. 2015; 10(3): e0122572. Published online 2015 Mar 27. doi: 10.1371/journal.pone.0122572
PMCID: PMC4376743

https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4376743/?report=reader

 

Analysis of the human monocyte-derived macrophage transcriptome and response to lipopolysaccharide provides new insights into genetic aetiology of inflammatory bowel disease.
Baillie JK, Arner E, Daub C, De Hoon M, Itoh M, Kawaji H, Lassmann T, Carninci P, Forrest AR, Hayashizaki Y; FANTOM Consortium., Faulkner GJ, Wells CA, Rehli M, Pavli P, Summers KM, Hume DA.
PLoS Genet. 2017 Mar 6;13(3):e1006641. doi: 10.1371/journal.pgen.1006641. [Epub ahead of print]
PMID: 28263993 Free Article

http://journals.plos.org/plosgenetics/article?id=10.1371/journal.pgen.1006641

 

Systemic lipopolysaccharide induces cochlear inflammation and exacerbates the synergistic ototoxicity of kanamycin and furosemide.
Hirose K, Li SZ, Ohlemiller KK, Ransohoff RM. J Assoc Res Otolaryngol. 2014; 15:555–70. doi: 10.1007/s10162-014-0458-8 PMID: 24845404

https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4141430/?report=classic

 

Lipopolysaccharide alters the blood-brain barrier transport of amyloid beta protein: a mechanism for inflammation in the progression of Alzheimer’s disease.
Jaeger LB, Dohgu S, Sultana R, Lynch JL, Owen JB, Erickson MA, et al.  Brain Behav Immun. 2009; 23:507–17. doi: 10.1016/j.bbi.2009.01.017 PMID: 19486646

https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2783557/

 

Restoration of impaired intestinal barrier function by the hydrolysed casein diet contributes to the prevention of type 1 diabetes in the diabetes-prone BioBreeding rat.
Visser JT, Lammers K, Hoogendijk A, Boer MW, Brugman S, Beijer-Liefers S, Zandvoort A, Harmsen H, Welling G, Stellaard F, Bos NA, Fasano A, Rozing J.
Diabetologia. 2010 Dec;53(12):2621-8. doi: 10.1007/s00125-010-1903-9.
PMID: 20853098 Free PMC Article

https://www.ncbi.nlm.nih.gov/pmc/articles/pmid/20853098/

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Expert Talk: David Perlmutter, MD Brain Inflammation, Autoimmune Disease and Nutrition

I just listened to the first ‘bonus’ video from the Autoimmune Revolution and I was STUNNED! ABSOLUTELY FABULOUS!!!  I am looking forward to the rest of the videos – I have a feeling it is going to end up being a great resource for me on this journey…  If you missed my previous post here is another link below to sign up for the free content!

After registering you will get an email confirmation with a link to the bonus content – The video I just watched was:

Expert Talk: David Perlmutter, MD Brain Inflammation, Autoimmune Disease and Nutrition

(Here is Dr. Perlmutters website http://www.drperlmutter.com/

https://www.thunderclap.it/projects/50763-the-autoimmune-revolution/embed

Ask Dr. Bernstein Tele-Seminar (relating to Type 1 & 2 Diabetics)

Dr. Bernstein is a Type 1 Diabetic who went against the main-stream way of thinking when it came to managing his diabetes. He is and type 1 diabetic endocrinologist with some great information!  Although those who are well versed in functional approaches may have some disagreements with some of his suggestions, overall he is still a wonderful resource especially for Type 1’s!!  I especially love his philosophy that all diabetics are entitled to the same blood sugar levels as non diabetics!

Ask Dr. Bernstein Webcast and Teleconference on, Wednesday, December 28th, you can listen to view the presentation for a limited time by going to this link :

dr.richard.k.bernstein

Watch December Seminar Here

The next webcast is January 25th at 8:00 pm EDT, 7:00 pm CDT, 5:00 pm PDT, and for our overseas guests, 12:00 am UTC (Wednesday).

Put all of the tele-seminar dates for 2017 in your calendar:   January 25th,  February 22nd, March 29th, April 26th, May 31st, June 28th, July 26th, August 30th,  September 27th, October 25th, November 29th, and December 27th, 2017.

If you have a friend who you feel would benefit from listening to the next tele-seminar, they can register here.

1969, formula & intestinal bacteria – What is the connection?

Do you have any idea what those three things have in common?

  • The year 1969
  • Infant Formula
  • Intestinal Bacteria

One of the first activities in my training is to research the history of our country’s National Food Guide.  So I visited the historical collection link from the USDA and ran a search for food guide.  I came across this one from 1969 and started scanning through it when this excerpt caught my attention:

Despite improvements in infant formulae, breast feeding is still strongly recommended. One explanation of the reason infants thrive better on human milk is that it promotes the growth of favorable intestinal bacteria which stop the growth of less desirable ones

A Food Guide for the Ages from baby to gramps; Author(s):Lewis, H.Subject(s):human nutrition , food science , family and consumer scienceFormat:p. 294-303.Language:EnglishYear:1969Series:Yearbook of agriculture

https://naldc.nal.usda.gov/naldc/download.xhtml?id=CAIN709013205&content=PDF

So I stop in my tracks staring at that last sentence. Shake my head. Exhale. So for more than 40 years we have known the importance of bacteria and their role yet when one looks at modern healthcare many are considered outcasts for thinking there is any correlation between the flora in our digestive system and the implications of a lack of the “good guys”.

Granted there is a movement which promotes the truth of the matter and I am thankful it is a growing movement.  What disturbs me though is how we have gone from bad to worse to downright… well I will let you fill in that blank.

How we can ignore the fact that formula does not promote a healthy environment is mind boggling. Why it is even remotely considered “safe” for infants to ingest something which deters their health is beyond me.  Once again I am reminded of John Yudkins work regarding sugar and the history behind high-fructose-corn-syrup as a staple in American food-like products.  So when I read that for nearly half a decade that we have known the adverse affects combined with nearly 60% of infants have had formula within 3 months of birth and by 6 months the figure reaches nearly 82%, I am in astonishment!

(CDC: Breastfeeding Report Card 2014) page 4 – two columns on the right
breastfeeding-2014

Now those are the averages – some states fair better and some fair worse.  It is very disturbing though if we know formula does not promote a healthy digestive system that pediatricians, nutritionists, doctors – all healthcare providers for that matter – are not adamant about doing everything possible to speak about the dangers of formula.

In thinking back at the birth of my children I recall getting a “mothers gift basket” at the hospital which contained various infant products. Formula was one of the products in that bag of samples along with a plethora of formula coupons that seemed to outnumber all the other products combined.

My children were in the NICU, one for seven days.  Very, and I mean very, few of those infants were on their mothers milk, instead they were fed formula of some kind.  My youngest child, that was in the NICU for a week, was almost exclusively breast-fed.  The only reason for not being exclusive is the staff did not adhere to my decision of exclusive breastfeeding and while I was waiting for the anesthesia to wear off after giving birth, they fed my child what they wanted, not what was best for my child.

Fast forward six months and my child was receiving formula as I searched for ways to help his sudden halting of gaining weight… One experience that I hope to blog about soon.

It is that mentality of acceptance that disrupting the digestive system is fine and dandy as to why we have epidemics left and right of childhood diseases.  Is there science to back up that claim?  That is a pretty powerful statement, I will admit!

If our premise is the Department of Ag made their claims with science to back it up and their conclusion that formula does not promote a healthy environment then how about we take a moment to examine the implications of a disrupted digestive system.  What is the logical outcome if we compromise our first wall of defense?

It is a building block – if the building materials are compromised what kind of a building are we going to have?  If we put bad gas in our vehicles what is going to happen? If we use spoiled ingredients in a recipe what is going to be the outcome?  So why would we expect anything different when we compromise the integrity of our digestive system?

I have binders, upon binders of studies that I have printed off in the last two years attempting to get to the root cause of my oldest child’s disease of Type 1 Diabetes. [We have zero family history of it]  There is a plethora of scientific evidence of many factors which play a role in the onset or in the continuation of this disease, and just as many as to factors that play a role in reversing it.

For instance:

2009 University Texas Southwestern – UNGER LEPTIN reverses Type 1

Proc Natl Acad Sci U S A. 2010 Oct 5;107(40):17391-6. doi: 10.1073/pnas.1008025107. Epub 2010 Sep 20.

http://www.ncbi.nlm.nih.gov/pubmed/20855609

***

Thioredoxin Interacting Protein: Redox Dependent and Independent Regulatory Mechanisms

ANTIOXIDANTS & REDOX SIGNALING Volume 16, Number 6, 2012

ª Mary Ann Liebert, Inc.
DOI: 10.1089/ars.2011.4137
Oded N. Spindel,1,2 Cameron World,1 and Bradford C. Berk1,2

…Recent Advances: Studies of the Hcb-19 mouse, TXNIP nonsense mutated mouse, demonstrate redox-mediated roles in lipid and glucose metabolism, cardiac function, inflammation, and carcinogenesis…

http://www.ncbi.nlm.nih.gov/pmc/articles/PMC3270053/pdf/ars.2011.4137.pdf

***

The list can go on and on –  Guess what the common factor is in all of them? I’ll give you a hint, its the research I reference in my post ‘Microbiome‘.  Eventually they lead to the digestive system and signaling that happens in the digestive process. Profound!  Although the more I think about it, not really.   I would strongly encourage you to visit Pubmed and do a search for a disease and another term to find links…. Such as  Cancer & Gut Flora where you would most likely find this in the top of the search results:

Breast Cancer. 2016 Oct 5. [Epub ahead of print]
Gastrointestinal microbiome and breast cancer: correlations, mechanisms and potential clinical implications.

Gastrointestinal microbiome plays as a symbiont which provides protection effect against invading pathogens, aids in the immune system development, nutrient reclamation and absorption as well as molecule breakdown.

https://www.ncbi.nlm.nih.gov/pubmed/27709424

Science seems to have the presupposition that our digestive system is the first line of defense – notice it aids the development of the immune system, not the other way around.  If it is compromised everything that follows will have a weak link.

They knew this in the 60’s and we know it today – so why my friends do we intentionally disrupt not only our own system but our children’s developing line of defense?

I know why I did – ignorance, peer pressure, medical expert pressure and fear.  Would love to hear your story!

Oh… to complete my project I had to locate the oldest guide… thus far I have found one from 1946

Microbiome

For some reason every time I hear the word microbiome I think of the Astrodome “the eighth wonder of the world”.  I get this picture in my head of this giant round egg shape with a ton of people inside all with a common purpose of being there… They are rooting for their team to win.  Lots of cheering going on and for the most part civil…  Every once in  while maybe a fight will break out… But I think that is primarily at soccer events… Anyway.. There is this boatload of folks in this enclosed area and only one team is going to win… Is it going to be a shut out? Does one team steamroll the other or maybe a close game going back and forth that goes well past the standard game time..

Then I think of our gut.  How it is populated with two different teams both vying for the win. What happens when one team dominates?  Does it matter which team has the upper hand?  It’s just some tiny bacteria what difference can they make if one dominates the other? [Edit 04/11/17 additional post connecting microbiome bacteria with diseases]

We rarely think of those “things” populating our guts and will venture to say we probably think even less about what happens when one group gets out of hand.  I often wonder why we are not taught things such as what these researchers from  Broad Institute of MIT and HarvardMassachusetts General Hospital (MGH), and the DIABIMMUNE found in their study on the connection between the microbiome and type 1 diabetes: (just to make sure you all read that right it is a number 1, not a 2, it’s not a typo, I say that because there are lots of articles about type 2 and various connections and type 1’s always are disappointed they don’t have a similar hope of finding meaningful connections)

  • Cambridge, Mass., February 5th, 2015
     

    In one of the largest longitudinal studies of the microbiome to date, researchers from the Broad Institute of MIT and Harvard, Massachusetts General Hospital (MGH), and the DIABIMMUNE Study Group have identified a connection between changes in gut microbiota and the onset of type 1 diabetes (T1D). The study, which followed infants who were genetically predisposed to the condition, found that onset for those who developed the disease was preceded by a drop in microbial diversity – including a disproportional decrease in the number of species known to promote health in the gut. These findings, published by Cell, Host & Microbe, could help pave the way for microbial-based diagnostic and therapeutic options for those with T1D.

https://www.broadinstitute.org/news/researchers-find-link-between-microbiome-type-1-diabetes

http://www.cell.com/cell-host-microbe/abstract/S1931-3128(15)00021-9

Well.  I guess that answers my question. Dare I visit PubMed for more research on the subject?  https://www.ncbi.nlm.nih.gov/pubmed?linkname=pubmed_pubmed&from_uid=27723761

Guess I better get my yogurt maker “dome” out of the cabinet and put it to use, maybe it won’t suffer the same fate as most of the sport domes seemed to face.

*Astrodome/Reliant Stadium photo By EricEnfermero – Own work, CC BY-SA 3.0, https://commons.wikimedia.org/w/index.php?curid=30810342

Sugar: The Rejected Truth

Most who know me have heard me preaching about sugar.  I often start the topic with the question:

  • Do you know the difference between a can of beer and a can of soda?
  • What about do you know the difference between how they each affect our bodies?  Specifically?
  • What about which organ processes the high-fructocse-corn-syrup? And which one the beer?

OH, well… My friend you have GOT to see the video by Robert H. Lustig, MD, UCSF Professor of Pediatrics in the Division of Endocrinology, where he explores high-fructose and how our bodies process it. For a direct link its on youtube titled:

Sugar: The Bitter Truth https://youtu.be/dBnniua6-oM

Now for the really, really sad part is over 40 years ago, there was a man who warned about the dangers yet he was squashed, so to speak.  Scientist John Yudkin was the first to sound the alarm about the excess of sugar in the diet of modern Americans. His classic exposé, Pure, White, and Deadly, clearly and engagingly describes how sugar is damaging our bodies, why we eat so much of it, and what we can do to stop. He explores the ins and out of sugar, from the different types—is brown sugar really better than white?—to how it is hidden inside our everyday foods, and how it is damaging our health.

In 1972, Yudkin was mostly ignored by the health industry and media, but the events of the last forty years have proven him spectacularly right. Yudkin’s insights are even more important and relevant now, with today’s record levels of obesity, than when they were first published. Brought up-to-date by childhood obesity expert Dr. Robert H. Lustig, this emphatic treatise on the hidden dangers of sugar is essential reading for anyone concerned about their health, the health of their children, and the wellbeing of modern society.

So if we never meet again, I implore you to look at sugar and its real effects on our bodies as they attempt to function. And I will leave you with one last question:

  • If a beer didn’t give a “buzz” would you then give it to your child or infant?

(Oh, do you remember my previous post “out of the box” where I touched on our hospitalization, when I wasn’t talking with docs, nurses, family members or friends I was watching this video – over and over – beating myself up because a dear dear friend had shared this with me many months prior yet I had not taken the warning to heart while thankful I had been provided an amazing avenue with a wealth of information!)