I don't think we understand these things the same way we understands mechanics
but we are trying to think of it the same way as if we were talking about a
car. We are so detached from what would normally be our diet in the "wild" that
it is not possible to know what the composition of a healthy human microbiota
should consist of... I see your point about the Vit D and autoimmune disease,
suppression/expression of particular strains, etc.! I don't know... wish that
we had a RESET button to stat from initial factory settings!
A true lover of wisdom has hands too busy to hold on to anything! He learns by
doing and every pebble in the path becomes her teacher! Oink
On Thursday, December 31, 2020, 10:24:16 AM EST, Silver Mouse
<mice42@xxxxxxxxx> wrote:
Thanks, interesting overview. I am a little confused by the statements that
Bacteroides fragilis and Vit. D are beneficial but that Vit. D is antagonistic
to Bacteroides. Am I misreading something?
On Thu, Dec 31, 2020 at 8:53 AM Domingo Pichardo <dmarc-noreply@xxxxxxxxxxxxx>
wrote:
How Your Gut Health Impacts Your Disease Risk
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How Your Gut Health Impacts Your Disease Risk
Harvard researchers have now identified the specific population of gut bacteria
that modulate localized and syst...
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- December 31, 2020
STORY AT-A-GLANCE
- A significant proportion of your immune system resides in your
gastrointestinal tract. Harvard researchers have now identified the specific
population of gut bacteria that modulate localized and systemic immune
responses to ward off viral invaders
- Bacteroides fragilis and other bacteria in the Bacteroides family initiate
a signaling cascade that induces the release of interferon-beta, which protects
against viral invasion by stimulating immune cells to attack the virus and
causing virus-infected cells to self-destruct
- Zonulin-mediated gut permeability plays a determining role in the
pathogenesis of many chronic inflammatory diseases. Zonulin is produced in
response to bad bacteria. It flushes the bacteria out by opening up the tight
junctions
- Aside from bacteria overgrowth, gluten is a powerful trigger of zonulin
release as the zonulin pathway misinterprets gluten as a potential harmful
component of a microorganism
- Chronic inflammatory diseases associated with dysregulation of the zonulin
pathway and leaky gut include autoimmune disorders, metabolic disorders,
intestinal diseases, neuroinflammatory diseases and cancer of the brain and
liver
More attention than ever is being put on your gut health, and understandably
so, considering a significant proportion of your immune system resides in your
gastrointestinal tract.1 As such, optimizing your gut microbiome is a
worthwhile pursuit that will have far-reaching effects on your physical health
and emotional well-being.
Mounting scientific evidence also continues to suggest a large component of
nutrition centers on nourishing health-promoting bacteria in your gut (and
elsewhere in and on your body). In doing so, you keep harmful microbes in check
and shore up your protection against chronic disease.
Disease Begins in Your Gut
ADHD, autism, learning disabilities, obesity, diabetes2 and Parkinson’s disease
are but a few of the conditions found to be influenced by your gut microbiome.
One 2020 scientific review3 goes so far as to say that all inflammatory disease
begins in the gut. Part of the blame is laid on excessive hygiene. In other
words, we’re “too clean” for our own good.
But your diet also plays a crucial role. The paper specifically addresses the
role of zonulin-mediated gut permeability in the pathogenesis of chronic
inflammatory diseases (CIDs). According to the author, Dr. Alessio Fasano,4 a
pediatric gastroenterologist, researcher and director of the Center for Celiac
Research and Treatment:5
“Apart from genetic makeup and exposure to environmental triggers,
inappropriate increase in intestinal permeability (which may be influenced by
the composition of the gut microbiota), a ‘hyper-belligerent’ immune system
responsible for the tolerance-immune response balance, and the composition of
gut microbiome and its epigenetic influence on the host genomic expression have
been identified as three additional elements in causing CIDs.
During the past decade, a growing number of publications have focused on human
genetics, the gut microbiome, and proteomics, suggesting that loss of mucosal
barrier function, particularly in the gastrointestinal tract, may substantially
affect antigen trafficking, ultimately influencing the close bidirectional
interaction between gut microbiome and our immune system.
This cross-talk is highly influential in shaping the host gut immune system
function and ultimately shifting genetic predisposition to clinical outcome.
This observation led to a re-visitation of the possible causes of CIDs
epidemics, suggesting a key pathogenic role of gut permeability.
Pre-clinical and clinical studies have shown that the zonulin family, a group
of proteins modulating gut permeability, is implicated in a variety of CIDs,
including autoimmune, infective, metabolic, and tumoral diseases. These data
offer novel therapeutic targets for a variety of CIDs in which the zonulin
pathway is implicated in their pathogenesis.”
Bacteria, Not Genes, Rule Your Health Destiny
Fasano points out that we simply do not have enough genes to account for the
myriad chronic diseases that can beset us. Genes also cannot explain the timing
of disease onset. To solve these mysteries, we must look to the microbiome, he
says, as “it is the interplay between us as individuals and the environment in
which we live that dictates our clinical destiny.”
Aside from the microbes themselves, the condition of your intestinal mucosa
also plays a significant role. “Although this enormous mucosal interface (200
m2) is not apparently visible, it plays a pivotal role through its dynamic
interactions with a variety of factors coming from our surrounding environment,
including microorganisms, nutrients, pollutants and other materials,” Fasano
explains.
While intracellular tight junctions used to be thought of as static and
impermeable, we now know this is not the case. As explained by Fasano, zonulin
is a powerful modulator of intestinal permeability. However, while zonulin is a
biomarker of gut permeability and plays a pathogenic role in in many chronic
inflammatory diseases, not all CIDs are caused by leaky gut.
Proposed Chain of Events Leading to CID
The graphic below, included in Fasano’s review but originating from an earlier
paper6 titled “Zonulin, a Regulator of Epithelial and Endothelial Barrier
Functions, and Its Involvement in Chronic Inflammatory Diseases,” co-written by
Fasano and Craig Sturgeon, details the “proposed chain of events leading to
chronic inflammatory disease.”
Under normal circumstances, a healthy homeostasis is maintained in your gut
lining such that when an antigen is encountered, no excess immune reaction
occurs (anergy). Under No. 2 in the graph, gut dysbiosis is setting in (i.e.,
an imbalance in the number and diversity of your gut microflora), causing
excess production of zonulin, which in turn makes the gut lining more permeable.
According to Fasano, the two most powerful triggers of zonulin release are
bacteria overgrowth and gluten. Zonulin is produced in response to bad
bacteria7 — it helps flush the bacteria out by opening up the tight junctions —
so bacteria overgrowth makes sense. But why does it respond to gluten?
Interestingly enough, the zonulin pathway misinterprets gluten as a potential
harmful component of a microorganism. That’s why gluten triggers zonulin
release. While not mentioned by Fasano, the herbicide glyphosate also triggers
zonulin, and is 10 times more potent than gluten!8
The subsequent permeability allows microbiota-derived antigen and endotoxin to
migrate from the lumen to the lamina propria (the connective tissue that is
part of the mucous membrane lining your intestine), thereby triggering
inflammation.
As the process continues to worsen (No. 3 in the graph), your adaptive immune
response kicks in, triggering the production of proinflammatory cytokines,
including interferon gamma (IFN-γ) and tumor necrosis factor alpha (TNF-α).
These cytokines further worsen the permeability, thus creating a vicious cycle.
Eventually (No. 4), mucosal tolerance is completely broken, resulting in the
onset of a chronic inflammatory disease.
Chronic Inflammatory Diseases Linked to Leaky Gut
The specific chronic inflammatory disease that ultimately emerges at the end of
all this depends in part on your genetic makeup, in part on the types of
exposures you’ve had, and in part on the composition of your gut microbiome. As
explained by Fasano:9
“Besides genetic predisposition and exposure to environmental triggers, the
pathogenesis of a variety of CIDs seems to involve mutually influenced changes
in gut permeability/Ag trafficking, immune activation, and changes in
composition/function of the gut microbiome.
Zonulin is a modulator of both epithelial and endothelial barrier functions …
Gut dysbiosis may cause the release of zonulin leading to the passage of
luminal contents across the epithelial barrier causing the release of
pro-inflammatory cytokines that themselves cause increased permeability
establishing a vicious loop leading to massive influx of dietary and microbial
Ags triggering the activation of T cells.
Depending on the host genetic makeup, activated T cells may remain within the
GI tract, causing CID of the gut … or migrate to several different organs to
cause systemic CID.”
Chronic inflammatory diseases associated with dysregulation of the zonulin
pathway include:
- Autoimmune disorders such as Celiac disease, Type 1 diabetes, inflammatory
bowel disease, multiple sclerosis and ankylosing spondylitis
- Metabolic disorders such as obesity, insulin resistance, nonalcoholic
fatty liver disease, gestational diabetes, hyperlipidemia and Type 2 diabetes
- Intestinal diseases such as irritable bowel syndrome, non-celiac gluten
sensitivity and environmental enteric dysfunction (a chronic disease affecting
the proximal intestine)
- Neuroinflammatory diseases such as autism spectrum disorder,
schizophrenia, major depressive disorder and chronic fatigue/myalgic
encephalomyelitis
- Brain and liver cancers
Gut Microbes Influence Genes and Can Influence Cancer Risk
While the inclusion of cancer on that list may seem odd at first glance, some
researchers believe the gut microbiome may actually end up being a game-changer
for cancer prevention and treatment.
Not only have gut bacteria been shown to influence gene expression,10,11
turning some genes on and others off, research12 published in 2018 found gut
microbes actually control antitumor immune responses in your liver, and that
antibiotics can alter the composition of immune cells in your liver, triggering
tumor growth.
Harvard Medical School researchers have identified the specific population of
gut microbes that modulates both localized and systemic immune response to ward
off viral invaders.
Certain gut bacteria also promote inflammation, which is an underlying factor
in virtually all cancers, whereas other bacteria quell it.13 The presence of
certain gut bacteria has even been shown to boost the patient’s response to
anticancer drugs.14
One way in which gut bacteria improve the effectiveness of cancer treatment is
by activating your immune system and allowing it to function more efficiently.
Researchers have actually found that when these specific microbes are absent,
certain anticancer drugs may not work at all.
Gut Bacteria Are Part of Your Antiviral Defense
Gut bacteria are also involved in your antiviral defense, recent research15
shows. As reported by Harvard Medical School November 18, 2020:16
“For the first time, Harvard Medical School researchers have … identified the
specific population of gut microbes that modulates both localized and systemic
immune response to ward off viral invaders. The work … pinpoints a group of gut
microbes, and a specific species within it, that causes immune cells to release
virus-repelling chemicals known as type 1 interferons.
The researchers further identified the precise molecule — shared by many gut
bacteria within that group — that unlocks the immune-protective cascade. That
molecule, the researchers noted, is not difficult to isolate and could become
the basis for drugs that boost antiviral immunity in humans.”
While the findings still need to be replicated and confirmed, they point to the
possibility that you might be able to enhance your antiviral immunity by
reseeding your gut with Bacteroides fragilis and other bacteria in the
Bacteroides family.17
These bacteria initiate a signaling cascade that induces the release of
interferon-beta that protect against viral invasion by stimulating immune cells
to attack the virus and causing virus-infected cells to self-destruct.
“Specifically, … a molecule that resides on the bacterium’s surface triggers
the release of interferon-beta by activating the so-called TLR4-TRIF signaling
pathway,” Harvard explains.18 “This bacterial molecule stimulates an
immune-signaling pathway initiated by one of the nine toll-like receptors (TLR)
that are part of the innate immune system.”
The Role of Vitamin D
Recent research also highlights the role of vitamin D in gut health and
systemic autoimmunity. The review article, published January 21, 2020, in
Frontiers in Immunology, notes:19
“Autoimmune diseases tend to share a predisposition for vitamin D deficiency,
which alters the microbiome and integrity of the gut epithelial barrier.
In this review, we summarize the influence of intestinal bacteria on the immune
system, explore the microbial patterns that have emerged from studies on
autoimmune diseases, and discuss how vitamin D deficiency may contribute to
autoimmunity via its effects on the intestinal barrier function, microbiome
composition, and/or direct effects on immune responses.”
As noted in this review, vitamin D has several direct and indirect regulatory
effects on your immune system, including promoting regulatory T cells (Tregs),
inhibiting differentiation of Th1 and Th17 cells, impairing development and
function of B cells, reducing monocyte activation and stimulating antimicrobial
peptides from immune cells.
That said, the relationship between vitamin D and autoimmunity is complicated.
Aside from immunosuppression, vitamin D also appears to improve autoimmune
disorders by the way it affects your microbiota composition and gut barrier.
The review cites research showing that your vitamin D status alters the
composition of your gut microbiome. Generally speaking, vitamin D deficiency
tends to increase Bacteriodetes and Proteobacteria while higher vitamin D
intake tends to increase prevalence of Prevotella and reduce certain types of
Proteobacteria and Firmicutes.
While research is still slim when it comes to vitamin D’s impact on gut
bacteria, especially in patients with autoimmune disease, vitamin D deficiency
and autoimmune diseases are known comorbidities and vitamin D supplementation
is often recommended for these patients.
Vitamin D Required for Tight Junction Maintenance
Better known is how vitamin D supports intestinal and immune cell defenses in
the gut. In fact, vitamin D is one of the crucial components required for
maintaining tight junctions. As explained in this review:20
“The intestinal epithelium is in constant interaction with the external
environment. Adequate barrier integrity and antimicrobial function at
epithelial surfaces are critical in maintaining homeostasis and preventing
invasion or overcolonization of particular microbial species.
A healthy intestinal epithelium and intact mucus layer are critical to protect
against invasion by pathogenic organisms, and vitamin D helps to maintain this
barrier function … Multiple studies found that vitamin D3/VDR signaling
modulates tight junction protein quantity and distribution …
As a ‘leaky’ protein that allows movement of ions into the intestinal lumen,
claudin-2 expression in the setting of functional vitamin D deficiency may
contribute to colitis pathology …
Vitamin D upregulates antimicrobial peptide mRNA and protein expression
including cathelicidin, defensins, and lysozyme … Antimicrobial peptides,
primarily secreted by Paneth cells in the gut, are important mediators of
microbiome composition … Defensins are secreted by epithelial cells, Paneth
cells, and immune cells, and are important components of the innate immune
response in the gut.”
How Vitamin D May Contribute to Autoimmune Disease
According to the authors, vitamin D deficiency may contribute to autoimmune
disease by affecting the microbiome and the immune system in the following
manner:
- Vitamin D deficiency or supplementation changes the microbiome, and
manipulation of bacterial abundance or composition impacts disease
manifestation.
- Lack of vitamin D signaling due to dietary deficiency can impair physical
and functional barrier integrity of the gut, thereby allowing bacterial
interactions to either stimulate or inhibit immune responses.
- Your innate immunologic defenses may be compromised if you are deficient
in vitamin D.
How to Optimize Your Gut Microbiome
All of this information should really drive home the point that optimizing your
gut flora and vitamin D level is of crucial importance for good health. By
reseeding your gut with beneficial bacteria, you can keep pathogenic microbes
and fungi in check and prevent them from taking over, and optimizing your
vitamin D will help avoid leaky gut.
Regularly eating traditionally fermented and cultured foods is the easiest,
most effective and least expensive way to make a significant impact on your gut
microbiome. Healthy choices include lassi (an Indian yogurt drink), cultured
grass fed organic milk products such as kefir and yogurt, natto (fermented soy)
and fermented vegetables of all kinds.
Although I'm not a major proponent of taking many supplements (as I believe the
majority of your nutrients need to come from food), probiotics are an exception
if you don’t eat fermented foods on a regular basis. Spore-based probiotics, or
sporebiotics, can be particularly helpful when you’re taking antibiotics.
They’re also an excellent complement to regular probiotics.
Sporebiotics, which consist of the cell wall of bacillus spores, will help
boost your immune tolerance, and because they do not contain any live bacillus
strains, only its spores — the protective shell around the DNA and the working
mechanism of that DNA — they are unaffected by antibiotics.
Antibiotics, as you may know, indiscriminately kill your gut bacteria, both
good and bad. This is why secondary infections and lowered immune function are
common side effects of taking antibiotics. Chronic low-dose exposure to
antibiotics through your food also takes a toll on your gut microbiome, which
can result in chronic ill health and increased risk of drug resistance. Last
but not least, you also need to avoid things that disrupt or kill your
microbiome, and this includes:
- Antibiotics, unless absolutely necessary
- Conventionally-raised meats and other animal products, as these animals
are routinely fed low-dose antibiotics, plus genetically engineered and/or
glyphosate-treated grains
- Processed foods (as the excessive sugars feed pathogenic bacteria)
- Chlorinated and/or fluoridated water
- Antibacterial soap and products containing triclosan
+ Sources and References Previous Article
A true lover of wisdom has hands too busy to hold on to anything! He learns by
doing and every pebble in the path becomes her teacher! Oink
--
<:3 )~
