Is the Gut the Starting Point of all Diseases?

Is the Gut the Starting Point of all Diseases?

Over 2,000 years ago, Hippocrates announced that all disease begins in the gut. As a result, Hippocrates is believed to be the father of medicine.

Medical experts believe that some of his suggestions and wisdom have stood the test of time. But one wonders if his advice that all disease begins in the gut is right.

This will be critically analyzed in this article. But, first, we will discuss everything you need to know about the link between your gut and your health.

 

Your gut and disease risk

Hippocrates was not entirely correct in suggesting that all disease begins in the gut. However, studies have shown that most chronic metabolic conditions start in the gut.

Your health is strongly affected by your gut bacteria and the integrity of your gut lining (1).

Several studies have shown that unwanted bacterial products known as endotoxins can leak through your gut lining and enter your general circulation (bloodstream) (2).

Your immune system immediately recognizes these molecules, which then launches an attack, resulting in inflammation (3).

Some authorities have hypothesized that this diet-inducing inflammation may cause leptin and insulin resistance, both driving factors for obesity and type 2 diabetes, respectively. It also causes fatty liver disease.

It is also important to note that inflammation is associated with many chronic health conditions (4).

Nevertheless, it is worth knowing that this area of research is advancing rapidly, and current theories may be overhauled before long.

 

How chronic inflammation affects the body

Your body responds to toxins, foreign invaders, and cell injury via inflammation.

Inflammation aims to help your body ward off these unwanted invaders and kickstart the repair of damaged structures.

There are two types of inflammation – acute inflammation and chronic inflammation.

Acute inflammation is considered a good thing – generally. It is a short-term inflammation, usually occurring after an injury or a bug bite. Without acute inflammation, viruses, bacteria, and other pathogens could easily invade your body, triggering sickness, and in some cases, causing death.

On the other hand, chronic inflammation is long-term and may be harmful. It has the potential to affect the whole body and launches inappropriate attacks on your body’s cells. Chronic inflammation is also known as systemic or low-grade inflammation (5, 6).

For instance, blood vessels such as the coronary arteries may get inflamed. The same goes for some structures in your brain (7, 8).

Chronic inflammation is believed to be one of the critical drivers of some of the world’s most serious health conditions, such as heart disease, obesity, type 2 diabetes, Alzheimer’s disease, metabolic syndrome, depression, among others.

However, the precise causes of chronic inflammation remain unknown.

 

The link between endotoxins and leaky gut

Your gut is home to trillions of bacteria. These bacteria are collectively referred to as gut flora.

Some of the bacteria in your gut are beneficial, while others are not. As such, the composition and number of bacteria in your gut can affect both your mental and physical health.

A substance called lipopolysaccharide is present in the cell wall of some gut bacteria – known as gram-negative bacteria. These lipopolysaccharides (LPS) are endotoxins (9).

LPS can trigger an immune reaction in animals. In addition, endotoxins can cause depression, fever, septic shock, and even muscle pains during acute bacterial infection (10).

Also, LPS may sometimes leak from the gut into the blood. The leakage may occur constantly or right after meals.

Endotoxins may leak into your blood along with fats, or they may penetrate the tight junctions in your gut lining. Under normal circumstances, these tight junctions are supposed to prevent the passage of unwanted substances across your gut lining.

When this occurs, the immune cells are activated. Although the amounts are not high enough to cause symptoms of infection like fever, they are high enough to trigger chronic inflammation, which may lead to health issues over time.

Leaky gut may be the primary mechanism behind chronic inflammation induced by diet.

When blood endotoxin levels increase to 2 – 3 times above average, a condition known as metabolic endotoxemia results.

 

The link between unhealthy diet and endotoxemia

Most studies on endotoxemia involve the injection of endotoxins into the bloodstream of test subjects (humans and animals). These studies show that injection of endotoxins causes a rapid onset of insulin resistance – a prominent feature of type 2 diabetes and metabolic syndrome (11).

It also shoots the level of inflammatory markers, indicating the activation of an inflammatory response (12).

It is also important to note that both human and animal studies suggest that an unhealthy diet causes a rise in endotoxin levels.

Animal studies indicate that a long-term, fatty diet may trigger endotoxemia, inflammation, obesity, insulin resistance, and metabolic syndrome (13, 14, 15).

Also, a 30-day study involving eight healthy human subjects found that a typical Western diet increased blood endotoxin levels by 71%. On the other hand, people on a low-fat diet had their blood endotoxin levels reduced by 31% (16).

Other studies have shown that unhealthy meals containing pure cream and moderate – and high-fat meals cause an increase in endotoxin levels.

However, since most fatty meals or diets also contain processed ingredients and refined carbs, these results should not be generalized to healthy, low-carb, or high-fat diets.

It is also believed that refined carbs increase the number of bacteria that produce endotoxins and leaky gut (gut permeability), thus amplifying exposure to endotoxins (17).

 

Summary

A lot of chronic metabolic ailments are believed to begin in the gut. What’s more, chronic inflammation is believed to be a driving force.

Inflammation triggered by bacterial endotoxins may be the primary link between an unhealthy diet, chronic metabolic diseases, and obesity.

On the other hand, chronic inflammation is quite complex, and medical researchers are just beginning to study the link between diet and inflammation.

There’s a big chance that the healthfulness of your lifestyle and diet affects your risk of inflammation and the conditions associated with it.

So, to keep yourself healthy, you must focus on a generally healthy lifestyle with adequate sleep, exercise, a diet comprising whole foods, and lots of prebiotic fiber.

 

Article resources

  1. Vajro, P., Paolella, G., & Fasano, A. (2013). Microbiota and gut-liver axis: their influences on obesity and obesity-related liver disease. Journal of pediatric gastroenterology and nutrition56(5), 461–468. https://doi.org/10.1097/MPG.0b013e318284abb5
  2. Jialal, I., & Rajamani, U. (2014). Endotoxemia of metabolic syndrome: a pivotal mediator of meta-inflammation. Metabolic syndrome and related disorders12(9), 454–456. https://doi.org/10.1089/met.2014.1504
  3. Escobedo, G., López-Ortiz, E., & Torres-Castro, I. (2014). Gut microbiota as a key player in triggering obesity, systemic inflammation and insulin resistance. Revista de investigacion clinica; organo del Hospital de Enfermedades de la Nutricion66(5), 450–459.
  4. Cani, P. D., Osto, M., Geurts, L., & Everard, A. (2012). Involvement of gut microbiota in the development of low-grade inflammation and type 2 diabetes associated with obesity. Gut microbes3(4), 279–288. https://doi.org/10.4161/gmic.19625
  5. Ferrero-Miliani, L., Nielsen, O. H., Andersen, P. S., & Girardin, S. E. (2007). Chronic inflammation: importance of NOD2 and NALP3 in interleukin-1beta generation. Clinical and experimental immunology147(2), 227–235. https://doi.org/10.1111/j.1365-2249.2006.03261.x
  6. Romeo, G. R., Lee, J., & Shoelson, S. E. (2012). Metabolic syndrome, insulin resistance, and roles of inflammation–mechanisms and therapeutic targets. Arteriosclerosis, thrombosis, and vascular biology32(8), 1771–1776. https://doi.org/10.1161/ATVBAHA.111.241869
  7. Alie, N., Eldib, M., Fayad, Z. A., & Mani, V. (2015). Inflammation, Atherosclerosis, and Coronary Artery Disease: PET/CT for the Evaluation of Atherosclerosis and Inflammation. Clinical Medicine Insights. Cardiology8(Suppl 3), 13–21. https://doi.org/10.4137/CMC.S17063
  8. Sankowski, R., Mader, S., & Valdés-Ferrer, S. I. (2015). Systemic inflammation and the brain: novel roles of genetic, molecular, and environmental cues as drivers of neurodegeneration. Frontiers in cellular neuroscience9, 28. https://doi.org/10.3389/fncel.2015.00028
  9. Raetz, C. R., & Whitfield, C. (2002). Lipopolysaccharide endotoxins. Annual review of biochemistry71, 635–700. https://doi.org/10.1146/annurev.biochem.71.110601.135414
  10. Opal S. M. (2010). Endotoxins and other sepsis triggers. Contributions to nephrology167, 14–24. https://doi.org/10.1159/000315915
  11. Mehta, N. N., McGillicuddy, F. C., Anderson, P. D., Hinkle, C. C., Shah, R., Pruscino, L., Tabita-Martinez, J., Sellers, K. F., Rickels, M. R., & Reilly, M. P. (2010). Experimental endotoxemia induces adipose inflammation and insulin resistance in humans. Diabetes59(1), 172–181. https://doi.org/10.2337/db09-0367
  12. Michie, H. R., Manogue, K. R., Spriggs, D. R., Revhaug, A., O’Dwyer, S., Dinarello, C. A., Cerami, A., Wolff, S. M., & Wilmore, D. W. (1988). Detection of circulating tumor necrosis factor after endotoxin administration. The New England journal of medicine318(23), 1481–1486. https://doi.org/10.1056/NEJM198806093182301
  13. Cani, P. D., Amar, J., Iglesias, M. A., Poggi, M., Knauf, C., Bastelica, D., Neyrinck, A. M., Fava, F., Tuohy, K. M., Chabo, C., Waget, A., Delmée, E., Cousin, B., Sulpice, T., Chamontin, B., Ferrières, J., Tanti, J. F., Gibson, G. R., Casteilla, L., Delzenne, N. M., … Burcelin, R. (2007). Metabolic endotoxemia initiates obesity and insulin resistance. Diabetes56(7), 1761–1772. https://doi.org/10.2337/db06-1491
  14. Kim, K. A., Gu, W., Lee, I. A., Joh, E. H., & Kim, D. H. (2012). High fat diet-induced gut microbiota exacerbates inflammation and obesity in mice via the TLR4 signaling pathway. PloS one7(10), e47713. https://doi.org/10.1371/journal.pone.0047713
  15. de La Serre, C. B., Ellis, C. L., Lee, J., Hartman, A. L., Rutledge, J. C., & Raybould, H. E. (2010). Propensity to high-fat diet-induced obesity in rats is associated with changes in the gut microbiota and gut inflammation. American journal of physiology. Gastrointestinal and liver physiology299(2), G440–G448. https://doi.org/10.1152/ajpgi.00098.2010
  16. Pendyala, S., Walker, J. M., & Holt, P. R. (2012). A high-fat diet is associated with endotoxemia that originates from the gut. Gastroenterology142(5), 1100–1101.e2. https://doi.org/10.1053/j.gastro.2012.01.034
  17. Spreadbury I. (2012). Comparison with ancestral diets suggests dense acellular carbohydrates promote an inflammatory microbiota, and may be the primary dietary cause of leptin resistance and obesity. Diabetes, metabolic syndrome and obesity : targets and therapy5, 175–189. https://doi.org/10.2147/DMSO.S33473

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