It’s no secret that obesity, diabetes, and metabolic disease are afflicting an incredible number of Americans; in fact, the prevalence of the metabolic syndrome in our country has reached an astonishing 34% and is continuing to rise. (1) This disease, characterized by long term low-grade inflammation, causes metabolic disturbances that lead to the development of complications such as nonalcoholic fatty liver disease, cardiovascular disease, and type 2 diabetes. This is a serious health problem for many Americans – one that isn’t going away any time soon – and determining the cause of these metabolic conditions is a top priority for obesity researchers across the country.
I’ve been writing about the connection between gut health and “diabesity” for quite some time now; I have an entire series on my website dedicated to the relationships between obesity, insulin resistance, metabolic syndrome and type 2 diabetes, and I believe that inflammation and leaky gut caused by gut dysbiosis are the key players in this metabolic epidemic. While the existence of leaky gut syndrome is still debated among doctors and scientists, it is clear to me that having healthy gut bacteria is crucial to maintaining a normal weight and functional metabolism.
Recently, a group of researchers in Brazil published a new review exploring the idea that intestinal permeability is a contributing factor to obesity. They identified three separate but related mechanisms: gut dysbiosis, an unhealthy dietary pattern, and specific nutrient deficiencies. These three risk factors likely interact to cause intestinal permeability and promote the development of the metabolic syndrome and obesity.
Gut dysbiosis and leaky gut
It is well documented that those with obesity have significantly impaired gut function compared to the general population. Obese individuals are shown to have problems with effective digestion and absorption of food, gastrointestinal illness, unstable or pathological intestinal microbiota, poor immune status, and overall lower wellbeing, suggestion a lack of gut health. (2) This gut dysbiosis is thought to cause increased permeability in the small intestine, allowing the entry of toxins called lipopolysaccharides (LPS) into the blood and triggering systemic inflammation.
While it is uncertain whether the alterations in gut health are the cause or consequence of obesity, the association between dysbiosis and obesity is strong. One theory is that the metabolic activity of gut microbiota contributes to weight gain by causing more calories to be extracted from the food passing through the gut. Small intestinal bacterial overgrowth (SIBO) may also play a role in intestinal permeability by increasing constipation, reducing pancreatic enzyme and gastric acid activity, and disturbing the microbiota and host immune system relationship.
Probiotic supplementation can help strengthen the tight junctions of the intestine, reducing overall permeability. Probiotics can have anti-inflammatory effects in the gut, regulating the production of inflammatory cytokines and reducing intestinal permeability. This demonstrates the benefits of a balanced microbiota in the gut to maintain the function of the intestinal barrier, particularly in obesity.
Dietary effects on leaky gut
Besides just the composition of gut bacteria, nutritional factors play an important role in permeability as well. The authors of this study suggest that there are two major components of the diet that can affect intestinal permeability: fructose and fat. Fructose is thought to damage the liver directly by increasing blood levels of LPS toxins, causing fatty liver, inflammation, and hepatic insulin resistance. These effects explain why high fructose consumption has been implicated in the development of metabolic syndrome.
As far as fat goes, the authors of this study suggest that fat is more efficient than carbohydrates at transporting LPS toxins to the liver through the formation of chylomicrons, molecules that deliver dietary fats from digestion to the liver. An increase in liver toxins was demonstrated to induce obesity, diabetes, and insulin resistance in rats, demonstrating why a high fat diet could exacerbate metabolic disease. The type of fat matters though; oleate, a monounsaturated fat, promotes the delivery of toxins to the liver, while butyrate, a short chain saturated fat, does not form chylomicrons or increase LPS toxins in the liver. It has also been found that changes in bile secretion are associated with altered intestinal permeability, and a decrease in bile allows for greater bacterial growth in the small intestine and more LPS being produced.
It is important that future research determine the type of fatty acids that increase intestinal permeability of endotoxins, and whether or not there is an interaction with the type and amount of bacteria in the gut. The authors of this review do suggest, however, that a combination of a high fructose and high fat diet can lead to an increase in toxin-related liver inflammation and weight gain, which is likely true. (Did someone say McDonald’s Value Meal?)
Nutritional deficiencies and leaky gut
There are several micronutrient deficiencies that the authors found to be associated with gut barrier function, specifically vitamin A, magnesium, zinc, vitamin D, and calcium. Vitamin A, zinc, and magnesium all help maintain tight junctions in the intestine and regulate endothelial differentiation in the gut, while vitamin D stimulates intestinal lining renewal and resistance to damage by modulating the immune system. Vitamin D and calcium play a joint role in maintaining the intestinal barrier by supporting the ATP-dependent pumps in the intestinal cells. In obesity, intake of these micronutrients is typically low, so deficiencies could play a significant role in exacerbating leaky gut conditions, especially when combined with intestinal dysbiosis and poor dietary choices. Therefore, having good intake of these micronutrients could be protective against the development of leaky gut and the inflammation and eventual obesity it can cause.
Obesity caused by a leaky brain?
One more potential issue (not discussed by this particular review paper) is the possibility that systemic inflammation can actually cause leakiness in the blood-brain barrier as well. (3) C-reactive protein (CRP), an inflammatory protein that is elevated in obesity, has been found to increase permeability of the blood-brain barrier, possibly leading to inflammation in the hypothalamus. This neuroinflammation can cause impairment of central nervous system (CNS) function, which has been associated with poor control of food intake, leptin resistance, and obesity.
Furthermore, LPS toxins, released into the blood by a leaky gut, can rapidly increase blood leptin concentrations; this increase is enhanced by the presence of CRP, which could explain why chronic inflammation is associated with a rise in both CRP and leptin in humans. In this way, a leaky gut and a leaky brain, both caused by systemic inflammation and exacerbated by gut dysbiosis, can increase the risk of developing obesity due to the disruption in CNS and leptin function.
Gaining weight? Check your gut health!
The take home message of this study is that the interplay of gut health and diet has a significant role in weight gain and risk of obesity and metabolic disease. If you are struggling to lose weight, you may be dealing with inflammation caused by leaky gut and dysbiosis. And remember, you don’t have to have gut symptoms to have a leaky gut! Weight gain alone could be your only symptom, but it’s an important one to consider.
There are many steps you can take to ensure a healthy gut. Using probiotics and prebiotics can change the quality of the microbiome in the gut, and there are certain dietary strategies that can help improve the strength of the tight junctions between intestinal cells. Other issues such as stress, antibiotic and other medication use, autoimmune disease, and dietary toxins can increase intestinal permeability, so these are gut health factors that must be addressed as well.
Just be sure that you take the necessary steps heal your gut if you’re struggling with weight loss despite making changes in your diet and lifestyle. It may be the last piece in the weight loss puzzle that you’re missing!