Last Updated on March 23, 2016 by Patricia Carter

SUMMARY:  Your gut microbiome allows you to live your life with health, wellness, and vitality, or illness and disease.  Without a doubt, the MICROBIOME RULES; WHAT IS MICROBIOME?

If you haven’t already done so, you should read the post, “Diet and other things Determines Our Microbiome” to be certain you are up to date not only with what this dynamic virtual organ is, but also are cognizant of the many factors that affect the microbiome.  

We can modulate this microbiome; the science is exploding daily with research that is unveiling the vast impact the gut microbiome has on all of our inner workings.

FOOD ALTERS THE MICROBIOME, with a focus here on celiac and autism, although the insight applies to all autoimmunes and chronic disease.

The post “Food Managing Autism and IBD: The Studies,” details the studies (and includes current ongoing clinical trials) showing dietary intervention (that heals the gut) can result in IBD remission or management of autism.  Such occurs through optimization of the microbiome since the food we feed the microbiome, determines the gut’s community of microbiota, whose role is to affect immunity, health, wellness, and vitality.  Thus, anyone looking to improve health needs to look first at optimizing the gut microbiome.

First I need to mention the study “Diet rapidly and reproducibly alters the human gut microbiome,” Nature, Dec. 2013.  It provides tons of detail showing that the microbiome shifts for subjects who ate solely either a plant based diet (grains, legumes, fruits and vegetables) or an animal based diet (meat, eggs, or cheese) for a short 5 day term.  While extreme “end of the scale” studies such as this can give interesting results, it is compromised by not taking into account the need for balance in the diet.  Also, the quality of the food consumed (grass-fed, pastured, GMO, organic) is not identified.  These considerations may alter the end results of this study.  In short:

1. The animal based diet had a greater impact on the gut microbiota than the plant based diet and caused the microbiome to change significantly; that shift occurred within 1 day of the diet reaching the distal gut microbiota and reverted back to the baseline structure 2 days after the diet stopped.
2. The animal-based diet was associated with increased expression of genes for vitamin biosynthesis, the degradation of polycyclic aromatic hydrocarbons which are carcinogenic compounds produced during the charring of meat, and the increased expression of β-lactamase genes.
3. Also worth noting:  Food-borne microbes from both diets transiently colonized the gut, including bacteria, fungi and even viruses.  For the animal diet, fermented dairy and cured meat bacterial strains (L. lactis, P. acidilactici  and  Staphylococcus) reached the gut in abundance.  No mention was made for the plant based diet though I don’t know if they ate fermented vegetables (sauerkraut, kimchi…)
4. One to two days post animal diet, fungal concentrations above baseline was apparent, and for the plant based diet, increased virus transcripts were apparent (plant pathogens reached the gut),
5. The animal diet, had significantly elevated bile acids (DCA) levels which increased the abundance of bile-tolerant microorganisms (Alistipes, Bilophila and Bacteroides) and decreased the levels of Firmicutes that metabolize dietary plant polysaccharides (Roseburia, Eubacterium rectale and Ruminococcus bromii).  Increased DCA is implicated in IBD and liver cancer.  Increased DCA inhibits the growth of Bacteriodetes and firmicutes phyla.
6. For the animal diet, increases in the abundance and activity of Bilophila wadsworthia support a link between dietary fat, bile acids and the outgrowth of microorganisms capable of triggering inflammatory bowel disease.
7. Conclusion: the gut microbiome shifts quickly, and the microbial activity mirrored differences between herbivorous and carnivorous mammals, reflecting trade-offs between carbohydrate and protein fermentation.

WHAT IS THE ROLE OF THE MICROBIOME?

Next up is Dr. Alessio Fasano, MD who explains in this podcast that the gut biome in general affects:

1. Our immunity (80 to 85 percent) determining our disease status,
2. Our brain operation and workings to the point of impacting thoughts, feelings, and emotions,
3. Our digestion and absorptive capability ranging from making every vitamin under the sun, to permitting leakage through which our immune system is stimulated.  That leakage either helps “fine tune” our immunity, or if chronic and causing inflammatory reaction, can lead to disease, autoimmunity and cancer.

Dr. Fasano is the Chief of Pediatric Gastroenterology and Nutrition at Massachusetts General Hospital, and is the Director of the Center for Celiac Research, which he founded in 1996.  He is also one of the most beloved figures in the gluten-free, celiac, and autoimmune communities.  Dr. Fasano recently published his book, “Gluten Freedom: The Nations Leading Expert Offers the Essential Guide to a Healthy, Gluten-Free Lifestyle” that reveals the latest developments in scientific research and treatment for the newly diagnosed, those already dealing with gluten-related issues, and/or for anyone who thinks they may have an issue with gluten (all of which has become a rapidly expanding audience).  This groundbreaking, authoritative guide is an invaluable roadmap. 

When we first crossed paths in 2003, he had just published the  groundbreaking study in the Annals of Medicine that established the prevalence rate of celiac disease at one in 133 people in the U.S.  I sympathized with his reaction to federal agency attempts to stymie his work as they told him, “Celiac disease isn’t in the US, it is across the pond.”  Understand, Dr. Fasano had completed his medical training at the University of Naples in Italy, and in 1993 he founded the University of Maryland School of Medicine’s Division of Pediatric Gastroenterology and Nutrition. Several years ahead of his “one in 133 people are celiac announcement”, in 2000, Dr. Fasano’s team had discovered “zonulin,” the molecule which regulates intestinal permeability (also known as “leaky gut”) and their totally ground-breaking research has linked an overproduction of zonulin (gluten is a clear known trigger for such in celiacs) to the development of a series of autoimmune diseases, including Type 1 diabetes, celiac disease and multiple sclerosis:

“Autoimmune diseases are characterized by tissue damage and loss of function due to an immune response that is directed against specific organs. This review is focused on the role of impaired intestinal barrier function on autoimmune pathogenesis. Together with the gut-associated lymphoid tissue and the neuroendocrine network, the intestinal epithelial barrier, with its intercellular tight junctions, controls the equilibrium between tolerance and immunity to non-self antigens.

Zonulin is the only physiologic modulator of intercellular tight junctions described so far that is involved in trafficking of macromolecules and, therefore, in tolerance/immune response balance.

When the zonulin pathway is deregulated in genetically susceptible individuals, autoimmune disorders can occur. This new paradigm subverts traditional theories underlying the development of these diseases and suggests that these processes can be arrested if the interplay between genes and environmental triggers is prevented by re-establishing the zonulin-dependent intestinal barrier function.

Both animal models and recent clinical evidence support this new paradigm and provide the rationale for innovative approaches to prevent and treat autoimmune diseases.”

Dr. Fasano continues to publish (October, 2013) expansion of the celiac zero tolerance parameters to include non-celiac gluten sensitive patients and notes that current studies likely will expand the components of wheat triggering such conditions to  include other grain proteins besides gluten:

“Recent studies raised the possibility that, beside gluten and wheat ATIs , low-fermentable, poorly-absorbed, short-chain carbohydrates can contribute to symptoms (at least those related to IBS) experienced by NCGS patients. These new findings need corroboration through additional studies involving larger numbers of subjects. If these studies will confirm these new findings, they will probably prompt a change in nomenclature from NCGS to wheat sensitivity to reflect the fact that, beside gluten, other components of wheat may be responsible for the symptoms reported by NCGS patients.”

NOW IS A GOOD TIME TO MAKE A CLEAR DISTINCTION BETWEEN CELIAC DISEASE AND THE IMMUNE SYSTEM ATTACK ON OTHER TISSUE, aka AUTOIMMUNE DISEASES  LIKE THYROID, THE BRAIN, etc,.. 

Dr. Fasano:  “Gluten (or more specifically, “gliadin”) is inflammatory because it cannot be digested by any human. If gluten is ingested, it causes a leaky gut**. If the gut doesn’t heal after ingestion of the gluten, it starts a war that has collateral damage of some kind. If that war is confined to the intestine, then the distress is in the function of the intestine. 

However, sometimes the immune cells, or the soldiers in the war, leave the intestine and then attack other types of tissues, like those in the gallbladder, thyroid, and brain. Inflammation because of gluten can even be a factor in diseases like autism and schizophrenia.”

** “leaky gut” is when excessive zonulin opens up tight junctions in the small intestine permitting undigested particles, bacteria, etc that ordinarily do not cross the intestinal barrier, to cross over.

Dr. Fasano notes that three components need to snowstorm for autoimmunity to develop:

1. genetic predisposition,

2. environmental trigger (gluten for certain, likely other components of wheat), and

3.  loss of intestinal barrier function (aka leaky gut) so as to stimulate the immune system.

ANTIBIOTICS, TOXINS WE INGEST, THE AIR WE INHALE, AND TOPICALS WE PLACE ON OUR SKIN AFFECTS THE MICROBIOME

Besides food affecting our microbiome (March 2012 summation of: “Human nutrition, the gut microbiome, and immune system: envisioning the future“), we know that what we inhale, toxins we ingest (even dental sealants), and what our skin absorbs all sees the gut sooner or later and our biome adjusts to deal with all the compounds and metabolites that it sees.  The bacteria  themselves  produce by-products, and this can be the source for optimizing or compromising the intestinal integrity.   A quick example of such is butyrate. a short chain fatty acid and by-product of the digestion of dietary fiber by gut microbes.  Butyrate producing bacterial species include:

• Clostridium butyricum
• Clostridium kleyveri
• Clostridium pasteurianum
• Butyrivibrio fibrisolvens
• Eubacterium limosum

Studies have shown that patients suffering from inflammatory bowel disease lack butyrate-producing bacteria and have lower levels of butyrate in their gut. However, butyrate’s anti-inflammatory properties (well documented in this Journal of Medical Microbiology paper) were attributed to its role as main energy source for the cells lining the colon. In summary: “butyric acid is the preferred source of energy for colonocytes. It affects cellular proliferation, differentiation and apoptosis. Moreover, butyric acid has well documented anti-inflammatory effects. Inhibition of histone deacetylase activity, resulting in hyperacetylation of histones, and as a consequence suppression of nuclear factor-kappa B activation, is a likely explanation. Secondly, it has been proposed that butyric acid reinforces the colonic defence barrier by increasing production of mucins and antimicrobial peptides. Thirdly, it has been shown that butyric acid decreases intestinal epithelial permeability by increasing the expression of tight junction proteins. Anti-inflammatory activities, combined with a strengthening of the mucosal barrier integrity, are ideal properties for therapeutic compounds against IBD-like syndromes. Indeed it has been shown that butyrate enemas can yield positive results in the treatment of active UC (Breuer et al., 1997).”

This study is the first to provide a molecular basis for the role of butyrate on the production of regulatory T lymphocytes:

“Butyrate, a by-product of the digestion of dietary fiber by gut microbes, acts as an epigenetic switch that boosts the immune system by inducing the production of regulatory T cells in the gut.”

Interestingly, the EPA regulates butyric acid (butyrates are esters of butyric acid)d as a toxic substance. Other slides presented in presentation (see “Services”) and in various posts throughout this site, relevant for visualizing the microbiome, include:

Snippet source: “Genome: Unlocking Life’s Code,” http://unlockinglifescode.org/explore/genomic-medicine/microbiome

This”High resolution Infographi​c of the Human Microbiome Project” was provided to me by The Huttenhower Lab, Department of Biostatistics, Harvard School of Public Health.

Slide source: biomeonboardawareness.com

AUTOIMMUNE BIO-MARKERS EXIST YEARS BEFORE DIAGNOSIS, with a focus on RA and systemic lupus erythematosus, but it’s insights applies to all autoimmunes):

Perhaps the most fascinating area of new research involves autoimmune bio-markers.  Certain foods we ingest (gluten being one) always opens up tight junctions in our gut lining and what leaks through, stimulates our immune system.

We are designed to work this way, and it should be a way that tunes up our immune system.  When this leakage goes awry, inflammation ensues and chronic inflammation leads to disease.  The immune system performs molecular mimicry and can target our tissues and organs that look similar to that leaking.  This can lead to autoimmunity.  The work of Dr. Yehuda Shoenfeld, MD shows that bio-markers exist years preceding autoimmunity diagnosis.  He has highlighted the pertinent sections of this study below.  If you stop the leakage triggering the overstimulated immune reaction, we think you can stop the progression of this self attack by the immune system.

This study provides insight into how far we’ve come in establishing that autoimmune bio-markers exist pre-disease (this paper’s focus is on RA and systemic lupus erythematosus, but it’s insights applies to all autoimmunes):

“Additional work is needed to develop valid means to classify and assess the pre clinical phases of  ARDs {autoimmune rheumatic disease}... related to classic public health schemes, in which the term ‘screening’ typically describes approaches aimed at identification of individuals who are in an asymptomatic or minimally symptomatic phase of disease, and who can undergo interventions to prevent progression to future disease…  “Multiple genetic, epigenetic and environmental risk factors for ARDs, particularly RA and SLE, have been identified, and some examples are presented in Table 2”  [shown below, these could be target factors modified at the pre-disease to preclude disease advancement to the clinical diagnosis stage}

“Importantly, in asymptomatic individuals with risk factors for ARD, many of whom will not develop future disease, the use of approaches such as lifestyle modification, vaccinations and antimicrobial or anti- inflammatory therapies with excellent safety records, is likely to be much more acceptable than prophylactic therapy with expensive drugs that are potentially associated with greater risks.”

http://www.ncbi.nlm.nih.gov/pmc/articles/PMC4090326/

http://www.ncbi.nlm.nih.gov/pmc/articles/PMC4090326/

This study also discusses current ongoing clinical trials using targeted disease-modifying therapies in individuals with early signs or symptoms of disease and/or a high risk of future ARD according to accurate predictive instruments to preclude advancement to the clinical diagnosis stage.  Note that better definitions of who to include in the ‘high-risk’ population remains to be developed:

“Notably in this regard, Examples of current ongoing clinical trials for an ongoing clinical trial is investigating rituximab for the prevention of future RA in individuals with no evidence of inflammatory arthritis upon physical examination but who have elevated levels of RF and ACPAs plus one or more of the following measures: increased levels of C-reactive protein or evidence of subclinical synovitis obtained using ultra-sonography or MRI.¹³⁹ In this trial, which began in the Netherlands in 2009, the individuals are being treated with a single dose of either rituximab or placebo, and the primary outcome is a decrease in the number of individuals who develop classifiable RA at 4 years. The results of this trial should be become available in the next few years and will probably provide important data regarding preclinic al RA and prevention of RA.”

I especially appreciate the conclusion of this study:

“We have focused herein on RA and SLE as model ARDs with a preclinical period of development, although most if not all ARDs are likely to have a preclinical stage of disease characterized by initiation and propagation of autoimmunity. Obtaining a clearer understanding of pre-clinical ARDs, including the genetic and environmental aetiological factors, and biomarkers that characterize the early stages of pathogenesis, would facilitate the develop predictive tools that ultimately enable screening and prevention strategies. Such screening and preventative initiatives could substantially reduce the burden that these diseases place on public health. Although further studies are needed to develop effective preventive approaches for all ARDs, if increased focus is placed on these issues by the biomedical community, other important organizations (including funding agencies) and society in general, we could reveal sufficient information on some ARDs to implement preventive strategies in the near future.”

■ Preclinical autoimmune rheumatic disease (ARD) can be defined as the presence of abnormalities in immune function and responses in the absence of clinically manifest tissue injury ■ Increasing data support the existence of preclinical phase of rheumatoid arthritis (RA) and systemic lupus erythematosus (SLE) that can be identified using biomarkers of autoimmunity and inflammation ■ RA and SLE could serve as models for understanding the mechanisms of disease development and, ultimately, prevention of other ARDs that in aggregate affect a substantial portion of the population ■ Understanding the preclinical phases of ARD might enable accurate identification of at-risk individuals and the development of preventive interventions that might modify risk factors or target immune pathways underlying disease ■ Identifying both the overall likelihood of future development of an ARD and the timing of onset of clinically apparent disease will be important for ‘personalized’ medicine and designing prevention trials ■ A range of studies focused on preclinical ARD are needed to clarify the natural history of ARD, and thus enable the development of screening programmes and early, potentially preventive, interventions.”

And in the case of Alzheimer’s,  this article discusses the emerging “Predictive Test” soon to be available but more so from the ethical and “how will people respond to knowing years in advance of a 90 percent chance of dementia” type of concerns.  Clearly, the science is moving towards identifying predictive bio-markers and one would hope, lifestyle modifications can be taught and implemented soon enough to preclude permanent tissue autoimmune damage.

THE PEARLS OF THIS POST:

What we eat really does feed the trillions of bacteria living in our gut’s biome altering the community of bacterial species. which in turn affects disease and inflammatory status.  Bio-markers of such exist years prior to diagnosis for autoimmune diseases.  Those optimizing the biome to preclude triggering an autoimmune disease, or those managing existing disease with diet, eat with a mission.  That mission is to deliberately manipulate the community of the trillion bacteria comprising our gut biome with every bite as well as implement “Whole Health Pillars” thereby modulating the biome.

The take away though really, is that all of us can modulate the biome, at our own pace, at our own comfort level, once we are aware of how to do such.  That is what I do, educate in a practical, easy to understand manner, how to optimize the gut biome through diet and lifestyle choices that we make. Who knew it could be so easy once made aware?
Last updated: March 23, 2016 at 5:39 am to optimize SEO.

In good health, wellness, and vitality,