Everything Everywhere All at Once Pt 1. Microbiome Connected to the Backbone

The Gut – Disc axis is just another example of how everything in the body connects.

The gut microbiota (which is well known to interact with dermal, placental, pulmonary and other microbiota, and to impact the liver, kidneys, cardiovascular system, brain etc), has now been shown to talk to the intervertebral discs and their microbiota. That conversation can be constructive or destructive, and in the latter case it leads to chronic pain and disability.

Intervertebral disc degeneration (IDD) is one of the many unpleasant signs of unsuccessful ageing. Extracellular matrix in the discs decays, and as a result they lose water, volume, elasticity and compressive strength. Disc deformation, back pain and stiffness ensue, and the condition can lead eventually to numbness and/or weakness as spinal nerves become compressed.

This very common pathology is the main cause of low back pain, which has been with us since Homo erectus – although probably not to the extent seen today (1).

Due to our sedentary lifestyle (which encourages lumbar wedging) and degraded diet (which damages bone and cartilage, as well as every other tissue), low back pain is prevalent and increasing (2). Worryingly, it is occurring in increasing numbers of younger patients (3, 4), and these young patients are increasingly being diagnosed with IDD (5). IDD is traditionally considered a condition of old age (ie 6), but I have seen lumber spine MRIs of young / middle-aged individuals that looked positively geriatric.

Lower back pain in adolescence significantly raises the likelihood of longer-term back pain in adulthood (7), and IDD generally worsens with time (8), so our future looks to be stiff, painful and altogether less vertical.

Current treatment consists of rest, physiotherapy, non-steroidal analgesics and local nerve blocks, with surgery for severe cases. These options are far from ideal, and new regenerative therapies involving ie stem cells and scaffolds are expensive and unproven (9). So, let’s get into the aetiological weeds.

Obesity (10), Type 2 diabetes (11) and smoking (12) are known risk factors; the worst 30–40-year-old lumbar spines I have seen were inside obese, diabetic smokers.

Veteran readers know that obesity, Type 2 diabetes and smoking all increase chronic inflammatory stress. Inflammatory stress degrades the extracellular matrix in a complex and potentially feed-forward process (13, 14). Matrix remodeling and decay are a central component in the ageing process, from wrinkling of the skin to neurodegenerative disease (15), and recent research has shown that this same process is involved in driving IDD (16, 17).

The modern diet and lifestyle induce chronic inflammatory stress (ie 18, 19), and this, together with diet-associated increases in obesity and diabetes, helps to explain why IDD is so prevalent, and on the rise.

The problems with anti-inflammatory drugs have lead many scientists to explore the potential role of natural anti-inflammatory compounds in prevention and treatment modalities. Three research groups reviewed the ability of carotenoids, polyphenols, coumarins, alkaloids, terpenoids and saponins to reduce inflammatory and oxidative stress, and ECM breakdown (20-22). Two more teams focused on omega-3 PUFAs (23, 24), with some positive clinical findings (25).

These papers provide a good rationale for putting phytochemicals and fish oil (preferably together) into clinical trials. To which I would add prebiotic fibers – and yes, it’s déjà vu (and the health protocol) all over again. Because …

A small but growing evidence base indicates that dysbiosis contributes to disc degeneration (26-27) via at least three mechanisms.

The first candidate is impaired colonic epithelial barrier function and the subsequent release of inflammatory endotoxins into the bloodstream, a consequence of dysbiosis already linked to many other chronic degenerative diseases (28-30). Dysbiosis-induced endotoxemia induces destructive remodeling of the extracellular matrix in conditions such as osteoarthritis and rheumatoid arthritis (31, 32) where, as in IDD, inflammation-mediated cartilage destruction occurs.

The second, gut dysbiosis causing local immunomodulation in affected joints (33), is closely related to the first The third, which a little more speculative but in my view persuasive, involves the translocation of enteric microbes into the physical environment of the vertebral discs, with subsequent colonisation and – again – local inflammatory breakdown of disc matrix (ie 34).

If any or all of these mechanisms is a driver of IDD, damping chronic inflammatory stress by combining fish oil and polyphenols with blended prebiotic fibers should be able to prevent, delay and perhaps even stop IDD progression.

The gut / disc connection is still a little theoretical, so let’s consider the evidence in stages.

The case for endotoxemia-mediated chronic inflammation and immuno-modulation in bone (35, 36) and cartilage disease (37, 38) looks very reasonable. There is strong evidence for gut dysbiosis contributing to altered disc microbiota (39) and disc degeneration in animal models (39, 40). Finally, humans with probable dysbiosis and confirmed IDD showed altered disc microbiota, with reduced butyrate-producing (anti-inflammatory) species and higher levels of inflammatory mediators (41-43). This is consistent with other research (14-17, 25-27).

Diet is important, and so is weight-bearing exercise. Too much (44) or too little (45) spinal loading damages the intervertebral discs, so find your Goldilocks zone. Steer a middle course between obesity and space travel.

Stress plays a role, as it does in most areas of health and disease. Chronic stress is increasingly recognized, for example, as a potentially exacerbating factor in rheumatoid arthritis (46, 47) and in inflammation in general (48). With the role of gut dysbiosis in IDD close to being confirmed, recent research showing that stress induces rapid changes in the gut microbiota (49), together with breakdown of the colonic epithelial barrier, endotoxemia and low-grade inflammation (50), may be very relevant indeed.

Unless you’re an elasmobranch, your backbone contains more than cartilage. By coincidence (or not – in my world, everything connects), microbiota also connect to vertebra. Recent research indicates that having the right microbiota protects these and other bones too, by encouraging constructive re-modelling which leads to repair and regeneration. (51)

Now hear the word of the Lord (52).

References:

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