Unless you’re a stranger to this blog, you know how highly I hold optimal metabolic health in regard to healing or preventing gut problems. A recent study found that 12.2% of the US population has optimal metabolic health. When you consider that this includes all adults over the age of 18, you may be a bit shocked. Me, not so much.
From my perspective, this number feels about right. People have an odd level of delusion when it comes to assessing their own health, and I’ve mentioned how I’ve been guilty of this. But I also see this all the time with people I work with even when it has nothing to do directly with metabolic health. For example, I’ve had at least half a dozen clients tell me their sleep is great eventually require a C-pap machine for a sleep apnea. The same holds true for all aspects of health.
I think this alarming data creates an ideal teaching moment for understanding the relationship between metabolic health and the gut. The criteria they used to assess optimal metabolic health is the same criteria we use for identifying metabolic syndrome. Those with optimal metabolic health have 0 of the 5 criteria used to assess metabolic syndrome. These criteria include:
- Waist circumference >40in for men, >35in for women
- Blood pressure >120/80mmHg
- Fasting glucose >100mg/dL, HgA1c >5.7%
- Triglycerides >150mg/dL
- HDL-C ≤50mg/dL for men, ≤40mg/dL for women
If you use the more lenient ATP III guidelines, the number of metabolically healthy is still under 20%(19.9%). Think about that, if we use the stringent numbers recommended today, for every 8 people in a room, only one person doesn’t have at least one of these problems. If we are lenient, it’s 1 in 5.
The worst part is that once people meet 3 of these 5 criteria and thus have metabolic syndrome, their risk for all chronic disease increases substantially, and chronic diseases of the gut are no exception. For example, people with metabolic syndrome have twice the risk of IBS than those who don’t. Another study found that those with metabolic syndrome have an 8.9x higher risk of gallstone disease.
Interestingly enough, it appears that in a lot of cases, gut dysfunction precedes development of the metabolic syndrome. In other words, gut problems creep up before you meet 3 of the above 5 criteria. In fact, this appears to be exactly the case with non-alcoholic fatty liver disease(NAFLD), it precedes metabolic syndrome.
In people with mild NAFLD, the risk for metabolic syndrome is 3.6x higher, for those with moderate to severe NAFLD, the risk is 9.4x greater. We also have data showing that people with high amounts of visceral fat or a larger waist circumference have a a 9.4x and 7.8x greater risk of IBS, respectively.
But when we really dig in to the dysfunction that comes with metabolic syndrome, NAFLD, and gut problems, the picture is crystal clear: A broken metabolism makes for a broken gut.
Metabolic syndrome, NAFLD, and the microbiome
Most aspects of the metabolic syndrome, as well as metabolic syndrome as a whole, associate strongly with NAFLD and microbial dysbiosis. Most people assume that this means that taking prebiotics or probiotics may be a useful therapeutic approaches to addressing metabolic syndrome. I don’t hold this view, and a recent study on NAFLD and this approach sums up my thoughts on the subject:
“The administration of probiotics and prebiotics as a cure-all remedy for all chronic diseases is not advocated, instead, the incorporation of evidence based probiotic/prebiotic formulations as adjunctive modalities may enhance lifestyle modification management strategies for the amelioration of NAFLD”
Simply put, this means that pre- and probiotics may be useful secondary approaches, but primary care centers around changing lifestyle. In fact, the only useful therapeutic approach to addressing NAFLD is fat loss. This is because the liver isn’t making fat out of thin air, it requires excess calories. There is no single initiating factor, NAFLD is a multi-hit problem that requires excess calories from either sedentary behavior or calorie over-consumption to progress to metabolic syndrome.
We can take a look at the commonalities between NAFLD and gut disorders identified in a recent review, specifically IBS, to get a pretty clear picture of why they associate so strongly with one another. In both, we see:
- Inflammation/immune activation
- Leaky gut
- Altered gut motility
- An impaired gut-brain axis
Thus, I don’t think the microbiome is a good therapeutic target. The reason for this is fairly straightforward. I believe that metabolic changes that lead to NAFLD and metabolic syndrome impair healthy digestion, which alters the microbiome. The change in the microbiome alters gut-liver communication, causing disease progression. This change is driven by lifestyle, and reinforced by the change in the microbiome, not caused by it.
So, in my model, the microbiome is a biomarker that perpetuates disease, not the underlying problem that causes it. Armed with this knowledge, we can dig a little deeper and look at how the changes that come with NAFLD and metabolic syndrome change gut function.
How metabolic dysfunction impairs gut function
There are a number of ways that the metabolic problems that form the criteria for the metabolic syndrome and the lifestyle factors associated with them cause gut dysfunction. The liver plays a large role in gut function by synthesizing bile acids and secreting factors that regulate intestinal permeability, while the gut helps the liver regulate bile synthesis and participates in glucose and triglyceride metabolism.
In fact, an argument can easily be made that the 2 components of the metabolic syndrome that relate specifically to liver metabolism, elevated blood glucose and triglycerides, are at the very least reinforced by changes in the microbiome. This is why probiotics and prebiotics seem like a viable option. They just don’t work because behavior drives the changes in the microbiome, and behavior is needed to reverse them. Which is probably why the most effective strategy at reversing NAFLD to date is lifestyle modification centered around dietary restriction, aerobic exercise, and resistance training.
Another way that metabolic dysfunction impairs gut function is through autonomic nervous system dysfunction. The autonomic nervous system helps regulate automatic processes including all aspects of digestion. People with metabolic syndrome with the presence of both impaired glucose regulation and high waist circumference experience autonomic dysfunction.
The reasons for autonomic dysfunction hit on both arms of the autonomic nervous system. Autonomic nervous system dysfunction may actually begin prior to metabolic syndrome through increased sympathetic nervous system activity. The sympathetic nervous system functions as the “fight or flight” wing of the autonomic nervous system. A recent review indicated that increased sympathetic nervous system activity likely plays a role in IBS, fibromyalgia, chronic fatigue syndrome, and interstitial cystitis.
Poor glycemic control and/or insulin resistance can also impair function of the vagus nerve, impairing sensory nerves that assist with timing in the gut as well as motor nerves that regulate gut motility. The vagus nerve is the conduit through which the brain and gut communicate and interfaces with the parasympathetic nervous system, which helps us “rest and digest”.
The damaging effects of hyperglycemia are also evident in nerves of the enteric nervous system, which is the resident nervous system in the gut. Enteric nerves are also damaged by hyperglycemia which essentially reinforces the same effects as damage to the vagus nerve. The effects of hyperglycemia on both enteric and the vagal neurons are believed to underlie:
- Altered GI motility
- Increased “leaky gut”
- Delayed gastric emptying(Gastroparesis) in people with Type 1 and Type 2 diabetes
Motility takes a second hit as the Interstitial cells of Cajal, which help regulate motility, are also damaged by hyperglycemia.
One final way that metabolic syndrome affects gut health may come as a surprise. In a study performed in 2017, researchers looked at the proximity of bacteria to the cells lining the colon in healthy subjects and those who were obese. The researchers found that people with poor glucose control, independent of obesity, had bacteria that were invading the inner mucus layer and causing inflammation by interacting with the gut wall, while people with healthy glucose control did not.
This doesn’t mean that all people with gut problems have metabolic syndrome. What it clearly illustrates is that if you do have a metabolic issue, you must address it before you can heal your gut. So if you checked off any of the 5 criteria for metabolic syndrome above, you have a target to go after. Of the criteria required for metabolic syndrome, blood glucose management seems to be incredibly important for fixing the gut.
But you don’t need Type 2 diabetes or metabolic syndrome to experience these problems. Even a relatively healthy person can experience hyperglycemia under the proper conditions, and these conditions aren’t even remotely rare. And as we age, the pump is primed to make these conditions more pathological. For example, after a woman goes through menopause, fat storage patterns change from a preference to subcutaneous fat around the butt, hips and thighs to a preference for metabolically damaging visceral fat.
Metabolic syndrome and NAFLD associate with gut disorders for multiple reasons. For one, the the physiological change that come with these disorders alter the way the gut functions. Additionally, the lifestyle factors that increase the risk for metabolic syndrome and NAFLD the impair the gut as well. This can be seen in the data showing an increased risk of IBS in people with greater waist circumference and visceral fat.
While it would be incorrect to say that gut disorders are caused by metabolic dysfunction, I think it’s clear that metabolic dysfunction makes functional gut disorders worse. Therefore, if your goal is to improve the health of your gut and have a fighting chance at reversing a chronic gut disease, fixing metabolic health should be an absolute priority.