Autoimmunity

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Re: Autoimmunity

Postby doogles on January 9th, 2018, 7:31 am 

Zetrique - "2) Of course, the gut has to be leaky for large molecule undigested proteins to pass into the blood stream. Could you please clarify this statement?"

As far as I can make out Zetrique, proteins are supposed to be broken down by digestion into their smaller amino acid or peptide components, and then they are ‘transported’ THROUGH the cells that line the alimentary canal (enterocytes) before reaching the blood stream. There is an excellent dissertation on this ‘transport’ on the following site - http://www.physiology.org/doi/full/10.1 ... 00018.2006 (Amino Acid Transport Across Mammalian Intestinal and Renal Epithelia by Stefan Bröer). I’ll insert a diagram that I pinched from that article and modified.

CELL JUNCTIONS.jpg


As amino acids, they are recognised as ‘self’ in the blood stream and do not elicit immunological responses as do all the high-molecular-weight cereal proteins that are showing up in the serological tests used in Functional Medicine. The latter are treated as ‘non-self’ and should not get into the blood stream in the first place.

Hence the theory of ‘Leaky Gut’. Somehow, they are bypassing the normal system of transport of smaller protein constituents THROUGH the enterocytes.

The most obvious route of entry is BETWEEN the cells. I think that this is a stage where we have best guesses and no evidence. Either zonulin metabolism has been compromised or else leucocytes have migrated through the cell junctions, reacted with ‘foreign’ proteins on the gut lining and thus caused damage to that lining. (I think I have seen one pathology report of microscopic damage in Crohn’s or Coeliac).

There is a parallel for this theory of leucocytes migrating between cells in the formation of ‘fatty streaks’, the earliest signs of atherosclerosis. Histopathology has shown that monocytes stream BETWEEN the cells lining arteries, apoptose into macrophages, pick up lipids, cholesterol, triglycerides plus other miscellaneous debris, and become atheromas.

I’m not sure if I have answered your question, but that’s my ‘working theory’ based upon the literature I’ve been reading.

I’m still finding the subject quite enlightening, Zetrique.
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Re: Autoimmunity

Postby zetreque on January 10th, 2018, 1:40 am 

aha,
The way that was worded I thought you meant that the gut is supposed to be leaky and undigested proteins are supposed to pass into the blood stream.

Good description though. :)

One thing I want to learn more about is how much the gut bacteria are responsible for break down vs our own enzymes.
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Re: Autoimmunity

Postby Braininvat on January 10th, 2018, 1:08 pm 

When I was a kid and there was this tv series in the late 60's about what the future would be like (title escapes me atm), there was not the slightest indication that exciting developments in poop transplants lay in our future. Where were you, Arthur C. Clarke? Isaac Asimov? Alvin Toffler?
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Re: Autoimmunity

Postby Hendrick Laursen on January 10th, 2018, 1:19 pm 

Fecal transplants definitely work when antibiotics wipe out other useful so-called "flora" and leave the resistant species like C. difficile to dominate.

That may be our last defence.
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Re: Autoimmunity

Postby doogles on January 11th, 2018, 7:04 am 

zetreque » Wed Jan 10, 2018 1:40 am wrote:aha,
The way that was worded I thought you meant that the gut is supposed to be leaky and undigested proteins are supposed to pass into the blood stream.

Good description though. :)

One thing I want to learn more about is how much the gut bacteria are responsible for break down vs our own enzymes.


I was totally blind to the fact that my phrasing of that sentence could be interpreted in that manner. It’s a good example of why we should always get someone else to edit anything we write before we publish books or important documents.

Re the relative role of gut bacteria in our digestion, as a practicing veterinarian in my earlier life, I was aware that ruminants were almost totally dependent on ruminal flora for the conversion of vegetation into absorbable nutrients. Well, partially dependent anyhow, because the carbohydrates produced by their ‘fermentation vat’ still had to be mixed with saliva to produce absorbable monosaccharides by ptyalin. Cattle spend as much time chewing their cud as in grazing. They produce between 10 and 40 gallons of saliva daily.

There has been a mass of research into this field in ruminants, but not that much apparently in humans.

Ruminants themselves do not produce enzymes to break down the pectins and cellulose in plant cell walls, but their gut microbiome does. They have cellulases and pectinases.

Other herbivores (equines and apes) employ their caeca as fermentation vats. I have not researched this aspect of human digestion yet, but I imagine that in our species and in canines, that the main gut microbiome is active in the caecum. And I would be surprised if that microbiome did not contain some pectinases and cellulases as in other herbivores.

Re faecal transplants - During my 25 years in country practice, I never missed an opportunity to do antibiotic sensitivity tests on ANY case of suspected bacterial infection. This included gastroenteritis in any species. I absolutely loathed using trial and error treatments. In my first months of practice, trial and error was all I had and it made me feel incompetent. I liked to know what I was doing. I would set up agar plates asap and use trial antibiotics on that plate. If I cultured a heavy growth of a homogeneous organism and found a circle of non-growth around an antibiotic, no matter how broad-spectrum that antibiotic was, I would use it – even if it sterilised the gut microbiome.

The fact of the matter was that after treatment, herbivores immediately began to graze on the pasture on which they and all of their friends had been defecating. Most dogs and cats in the 1950s/60s were fed by throwing meat and bones onto the ground that had been soiled over years by their own faeces. Thus, faecal transplants were automatic. In the case of dogs, the meat was often taken off and buried till it went rotten anyhow. My results were excellent and such that non-responses turned out to have rather esoteric ‘other’ conditions. I always sought permission to do autopsies at my own expense when patients did not respond.

One of the papers I have somewhere on my computer indicated that in human beings, 30% more of people delivered by caesarean section develop auto-immune diseases. A ploy being used by functional medicine practitioners now apparently is to insert a sponge into the vagina of the mother during the operation and when the baby is delivered, to wipe this sponge over the baby’s face and lips.

I’ve never attended a natural human birth, but if it’s anything like other species there would be plenty of faeces soiling the birth area during natural delivery.

We are possibly becoming too ‘hygienic’ for our own good.

But talking about human hygiene - The basic advice is to wash our hands after we go to the toilet. But think about the minutiae of this procedure for a second. With average toilet designs, it’s almost impossible to use toilet paper without getting some soiling of our fingers. Before we leave the cubicle, we have to pull up clothes, press a button to flush, use our hands to open the cubicle door and then to turn on the tap at the wash basin before cleaning our hands. So the odds are that we contaminate all of these contact points before we leave.

To avoid contamination of our clothing in the first instance, we would have to have a wash basin right next to the toilet bowl that can be turned on with a foot pedal or elbow, wash with a disinfectant as thoroughly as would a surgeon before an operation and then dry off with hot air or paper towelling. Then we could adjust our clothing and hope that everyone else using the facility has done the same before we press the flush button, open the door of the cubicle, or the door of the toilet if in public places, and then the rail of the stairway, the handles of the shopping trolley at supermarkets, and those places that everyone else has contacted with their hands on the way.

So, here’s the dilemma. Should we leave this alone and share our faecal saprophytes and commensals, and possibly be healthier overall, or should we upgrade ALL of our toilets so that a wash basin is available before clothing adjustment, just in case a pathogenic organism MAY be about?

And to Hendrick – Just out of curiosity, in what manner is a human faecal transplant administered?
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Re: Autoimmunity

Postby zetreque on January 11th, 2018, 11:08 am 

I had read somewhere a theory for the "useless" appendix in humans was actually to replenish the intestines with bacteria after a diarrhea event. I remember the author having some evidence to this.

It is also interesting that many animals actually seek out eating dirt or feces when they are not feeling well. It makes me wonder a lot about instinct vs acquired knowledge. Last month two people I know had dogs that were not feeling well and eating excess dirt.

The caesarean section autoimmunity theory that I have often read about is valid to me as I was born that way and I have had more issues than should be normal.

What I have never understood however is how it actually makes that big of difference when the anus colon is adjacent to but not in direct contact with the birth canal.
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Re: Autoimmunity

Postby zetreque on January 11th, 2018, 11:21 am 

zetreque » Thu Jan 11, 2018 7:08 am wrote:
What I have never understood however is how it actually makes that big of difference when the anus colon is adjacent to but not in direct contact with the birth canal.


I guess this would help explain it.
https://www.romper.com/p/what-happens-to-your-butt-hole-when-you-give-birth-heres-what-to-prepare-for-15624
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Re: Autoimmunity

Postby Hendrick Laursen on January 11th, 2018, 2:26 pm 

doogles » January 11th, 2018, 1:04 am wrote:
And to Hendrick – Just out of curiosity, in what manner is a human faecal transplant administered?



Hi doogles,

Multiple modalities are available now, including but not restricted to per os (as a capsule), nasogastric tube, nasoduodenal tube, via colonoscopy, enema, etc.

Fecal Microbiota Transplant is so effective that it outdoes some classic antibiotics routinely used against CDI (Clostridium difficile Infection) such as vancomycin, and some consider it to be first line therapy against CDI. (Since antibiotics usually make it worse, as CDI is highly resiliant and resistant, so antibacterials end up wiping out normal flora, dramatically aggravating the situation).

Good intro:
https://en.m.wikipedia.org/wiki/Fecal_microbiota_transplant
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Re: Autoimmunity

Postby doogles on January 12th, 2018, 6:03 am 

Excellent reference Hendrick.

I'm surprised that they use quantities up to 300 g.

It seems a large amount to introduce in one hit with a risk of upsetting a current status quo. I was thinking more in terms of a one gram capsule with the hope that the organisms would reproduce rapidly and fill a niche without forcing a change in balance.

But if it works, so be it
'
BTW, thanks for the PM correction re apoptosis and differentiation. I had problems with the 'reply' and 'send' prompts on that site.
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Re: Autoimmunity

Postby Hendrick Laursen on January 12th, 2018, 1:57 pm 

You're very welcome doogles. ;)
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