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Putting Out the Fire: Gut Flora and the Inflammatory Cycle

It’s funny. Once you realize the relationship between nutrition, disease, health, and metabolism is complicated, complex, and completely interdependent, things somehow get a bit simpler. Everything is connected to everything else. Chronic stress begets chronic inflammation, which chronically elevates cortisol, which induces insulin resistance and belly fat accumulation. Celiacs are usually intolerant of casein, too. Diabetics get heart disease more and have higher cancer mortality rates. Diabetics are often insulin resistant and usually overweight. Celiacs are often Type 1 diabetics. The overweight sleep less, work more, and get less sun than leaner folks.

Now, it’d be difficult to map out the precise relationships between myriad maladies and their nutritional triggers or risk factors. To do so definitively would produce a mostly unreadable mess. What we do instead is speculate. Make good guesses based on clinical, anecdotal, even anthropologic evidence. We look at what those people with chronic inflammation, obesity, autoimmune disease, diabetes, and celiac are eating, sleeping, and exercising, and we go from there. The precise physiological mechanisms behind some of these relationships have yet to be fully teased out, but the relationships exist and that’s usually enough to get results. Hence, simplicity.

Okay, maybe relative simplicity is a better descriptor. My point is this: the human body is incredibly complex, its every process multi-factorial. As soon as we decipher cause-and-effect, we’re beset with more questions. There are intermediary steps along the way. What’s causing the “cause” to have the “effect”? What’s it like on the cellular level? How many steps, how many mechanisms are at play between cause and effect? It’s almost like there’s an infinite regression [1] of steps simply because there are so many things going on at the cellular level to make basic physiological processes go.

We do know that inflammation, especially chronic, systemic inflammation seems to be involved in nearly every disease under the sun. Obesity, cancer, heart disease, autoimmune disease – if it’s killing people, increasing health care costs, and reducing quality of life, inflammation is bound to be involved at some level. That makes things easier, in my opinion, because we have a good idea how to avoid chronic inflammation, and that should take care of half the battle.

Avoid sugars [2], grains [3], legumes [4], and processed vegetable oils [5].

Eat lots of healthy animals [6] and their fat [7], along with vegetables [8], and fruits [9] and nuts [10] on occasion.

Get plenty of sleep [11].

Get regular exercise [12] – but not too much, and keep the Chronic Cardio [13] to a minimum.

Get regular sun [14].

Don’t stress [15].

Now there’s a new (ancient) wrinkle to consider in the fight against chronic inflammation: the gut flora. Understanding our own bodies is difficult enough, but now we’ve also got to make sense of how the droves of foreign (but symbiotic) microbes living in our guts interact with our health. We know a fair amount already.

Our relationship to gut flora is confusing and rather precarious. If the right conditions are met, we exist in harmony. If good bacteria is stable, breaking down fiber (like pectin and inulin) into short chain fatty acids (like butyrate [16]), and working harmoniously with the body, gut inflammation is suppressed, intestinal permeability is reduced, and multiple health biomarkers (lipids, insulin) improve. But we must remember – gut flora doesn’t exist for our benefit. Even if gut flora species were sentient, they’d only be acting out of self-interest. They wouldn’t “care” about us. They’re just trying to survive. It just so happens that keeping us happy by mediating immune responses and tight junction function, helping identify harmful intruders, and producing short chain fatty acids like butyrate puts the flora in good standing with our immune systems. They scratch our back, we provide room and board and don’t dispatch antibodies to destroy them.

Gut flora influences the human immune response [17] (provides a blockade against damaging bacteria; gives a “safe word” to avoid the immune system wasting resources on attacking; influences size of the thymus). Mice without gut flora have a severely truncated immune response, for example.

Now what is the primary immune response to damaging stimuli? Inflammation [18]. In correct doses, inflammation is a boon, necessary for healing and protection from foreign invaders. But in excess, inflammation is at the heart of many diseases. Gut inflammation especially is associated with a number of autoimmune diseases. Leaky gut, or intestinal permeability, for example, is associated with inflammation of the gut [19], and with small intestinal bacterial overgrowth.

Small intestinal bacterial overgrowth, or SIBO, occurs when the gut flora is compromised. Remember, normal gut flora acts as a physical barrier to foreign flora; they are stubborn tenants, old ornery relics of the neighborhood who refuse to leave and who dissuade pathogenic flora from settling in. If the good gut flora is gone or disrupted, pathogenic bacteria can populate the gut at will. The result is SIBO, and it leads to gut inflammation and intestinal hyper permeability.

Barriers called tight junctions guard the pathways between intestinal epithelial cells. Tight junctions, and their governing toll-like receptors [20], rely on cooperative gut flora in order to know which proteins and which molecules are to be barred entry; compromised gut flora and leaky tight junctions allow proteins and other molecules to enter the blood stream haphazardly. If damaging proteins (like lectins from grains and legumes, for example, or gluten [21])  slip into the blood stream, they are recognized and the immune system responds as it normally would to foreign, damaging intruders: with inflammation.

In correct doses, inflammation is a boon, necessary for healing and protection from foreign invaders…

See where I’m going with this?

It’s all a vicious cycle. Inflammation leads to disturbed gut flora (or maybe it’s the other way around – the classic chicken and the egg dilemma), SIBO, malfunctioning toll-like receptors, and leaky gut, allowing proteins to enter the body and provoke an inflammatory response by the immune system. More inflammation, more bacterial overgrowth, maybe a bout of antibiotics thrown in for good measure which wipes out the bacteria, leaving a clean slate and prompting another mad dash by microbes to fill the vacancies, and the result is – potentially – a permanently altered/disrupted distribution of gut flora both supporting and supported by chronic systemic inflammation. Where does it end? How do we fix it?

Common tactics don’t seem to work too well. Excessive antibiotic usage negatively impacts the population of gut flora, destroying the good with the bad. Think indiscriminate carpet-bombing. Living a sterile, bacteria-less early existence [22] (dirt avoidance, lack of breastfeeding, C-section) has a similar effect by limiting the variety and the amount of gut flora from the very start. Whether you had it and lost it or never had it at all, the effect is the same: suboptimum levels of intestinal bacteria. Neither avoiding nor eradicating bacteria is the solution.

So what is the solution, beyond traveling back in time to populate your infant gut with probiotics?

I mentioned Dr. Art Ayer’s Cooling Inflammation [23] blog last week, and I’m going to do so again. First, Art suggests adopting an anti-inflammatory diet. His dietary recommendations are essentially identical to mine – high SFA [24], moderate animal protein [25], low O-6, O-3 supplementation [26], leafy greens [27], some fruit and nuts. He also suggests probiotic [28] usage, either in supplement or whole food form (yogurt [29], kefir [30], sauerkraut [31]), to repopulate the gut with good flora. The next one is the most interesting: eating fibrous vegetables fresh from the garden, unwashed, in order to feed your new flora as well as introduce new bacteria and new digestive enzymes to diversify your gut’s digestive skill set (similar to how seaweed-borne bacterial enzymes taught Japanese gut flora to break down seaweed [32]). Foods like jicama [33], onions, garlic, and Jerusalem artichokes provide the prebiotic inulin (a type of fiber) which gut flora consume and convert to helpful short chain fatty acids.

It seems like a solid, familiar plan. The basic Primal Blueprint diet is already anti-inflammatory, and we promote the consumption of fermented foods [34] and probiotics, but perhaps a greater focus on feeding flora prebiotics is in order, too. It makes sense.

If there’s anything I’ve learned as a married father of two, it’s that keeping the organisms living under your roof happy and well-fed is absolutely essential if you intend to live a low-stress, anti-inflammatory life.

Thanks for reading and Grok on! [35]