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.
Bacteria, Not Genes, Rule Your Health DestinyFasano points out that we simply don't have enough genes to account for the myriad chronic diseases that can beset us. Genes also can't 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.
Proposed Chain of Events Leading to CIDThe graphic below, included in Fasano's review but originating from an earlier paper 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.
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.
Chronic Inflammatory Diseases Linked to Leaky GutThe 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:
"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."
- 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 RiskWhile 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.
Gut Bacteria Are Part of Your Antiviral DefenseGut bacteria are also involved in your antiviral defense, research shows. As reported by Harvard Medical School on Nov. 18, 2020:
"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."
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.
The Role of Vitamin DRecent research also highlights the role of vitamin D in gut health and systemic autoimmunity. The review article, published on Jan. 21, 2020, in Frontiers in Immunology, notes:
"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, written by researchers at Cleveland Clinic, 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 the 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.
Vitamin D Required for Tight Junction MaintenanceBetter 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:
“The intestinal epithelium [tissue] is in constant interaction with the external environment [in the form of food]. Adequate barrier integrity and antimicrobial function at epithelial surfaces are critical in maintaining homeostasis and preventing invasion or overcolonization of particular microbial species.
How Vitamin D May Contribute to Autoimmune DiseaseAccording 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 MicrobiomeAll 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, 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