More than 2,000 years ago, Hippocrates — the father of modern medicine — suggested that all disease begins in the gut.

While some of his wisdom has stood the test of time, you may wonder whether he was right in this regard.

This article tells you all you need to know about the connection between your gut and disease risk.

Though Hippocrates was incorrect in suggesting that all disease begins in your gut, evidence shows that many chronic metabolic diseases do.

Your gut bacteria and the integrity of your gut lining strongly affect your health. (1).

According to numerous studies, undesirable bacterial products called endotoxins can sometimes leak through your gut lining and enter your bloodstream (2).

Your immune system then recognizes these foreign molecules and attacks them — resulting in chronic inflammation (3).

Some hypothesize that this diet-induced inflammation may trigger insulin and leptin resistance — driving factors for type 2 diabetes and obesity, respectively. It’s also believed to cause fatty liver disease.

At the very least, inflammation has been strongly linked to many of the world’s most serious conditions (4, 5, 6).

Nonetheless, keep in mind that this area of research is rapidly developing, and current theories may be overhauled in the future.


Though not all disease begins in the gut, many chronic metabolic conditions are hypothesized to be caused or influenced by chronic gut inflammation.

Inflammation is your immune system’s response to foreign invaders, toxins, or cell injury.

Its purpose is to help your body attack these unwanted invaders and begin repair of damaged structures.

Acute (short-term) inflammation, such as after a bug bite or injury, is generally considered a good thing. Without it, pathogens like bacteria and viruses could easily take over your body, causing sickness or even death.

However, another type of inflammation — called chronic, low-grade, or systemic inflammation — may be harmful, as it’s long term, may affect your entire body, and inappropriately attacks your body’s cells (7, 8).

For example, your blood vessels — such as your coronary arteries — may be inflamed, as well as structures in your brain (9, 10).

Chronic, systemic inflammation is now believed to be one of the leading drivers of some of the world’s most serious conditions (11).

These include obesity, heart disease, type 2 diabetes, metabolic syndrome, Alzheimer’s disease, depression, and numerous others (12, 13, 14, 15, 16).

Still, the exact causes of chronic inflammation are currently unknown.


Inflammation is your immune system’s response to foreign invaders, toxins, and cell injury. Chronic inflammation — involving your entire body — is believed to drive many serious diseases.

Your gut houses trillions of bacteria — collectively known as your gut flora (17).

While some of these bacteria are beneficial, others are not. As a result, the number and composition of your gut bacteria can greatly affect both your physical and mental health (18).

The cell walls of some of your gut bacteria — called gram-negative bacteria — contain lipopolysaccharides (LPS), large molecules also known as endotoxins (19, 20).

These substances can cause an immune reaction in animals. During an acute bacterial infection, they can lead to fever, depression, muscle pains, and even septic shock (21).

In addition, these substances can sometimes leak from the gut into the bloodstream — either constantly or right after meals (22, 23).

Endotoxins may either be carried into your blood circulation along with dietary fat, or they may leak past the tight junctions that are supposed to prevent unwanted substances from getting across your gut lining (24, 25).

When this happens, they activate immune cells. Though their amounts are too small to cause symptoms of an infection like fever, they’re high enough to stimulate chronic inflammation, causing issues over time (26, 27).

Therefore, increased gut permeability — or leaky gut — may be the key mechanism behind diet-induced chronic inflammation.

When endotoxin levels in your blood increase to levels that are 2–3 times higher than normal, this condition is known as metabolic endotoxemia (28).


Some bacteria in your gut contain cell wall components called lipopolysaccharides (LPS), or endotoxins. These can leak into your body and trigger inflammation.

Many studies on endotoxemia inject endotoxins into the bloodstream of test animals and humans, which has been shown to cause a rapid onset of insulin resistance — a key feature of metabolic syndrome and type 2 diabetes (29).

It also leads to an immediate increase in inflammatory markers, indicating that an inflammatory response has been activated (30).

Additionally, both animal and human research indicate that an unhealthy diet may cause elevated endotoxin levels.

Animal studies suggest that a long-term, high-fat diet may cause endotoxemia, as well as inflammation, insulin resistance, obesity, and metabolic disease as a result (26, 31, 32).

Similarly, in a 1-month human study in 8 healthy people, a typical Western diet lead to a 71% increase in blood endotoxin levels, while levels decreased by 31% in people on a low-fat diet (33).

Numerous other human studies also observed that endotoxin levels increased after an unhealthy meal including pure cream, as well as high-fat and moderate-fat meals (22, 34, 35, 36, 37).

Still, as most of the high-fat diets or meals also contained refined carbs and processed ingredients, these results should not be generalized to a healthy, high-fat, low-carb diet based on real foods and including plenty of fiber.

Some researchers believe that refined carbs increase endotoxin-producing bacteria, as well as gut permeability — amplifying endotoxin exposure (38).

A long-term study in monkeys on a diet high in refined fructose supports this hypothesis (39).

Gluten may also increase gut permeability due to its effects on the signaling molecule zonulin (40, 41).

The exact dietary causes of endotoxemia are currently unknown. In fact, multiple factors are likely at play — involving dietary components, the setup of your gut bacteria, and numerous other factors.


Studies in both animals and humans show that an unhealthy diet can raise endotoxin levels in your blood — possibly driving metabolic disease.

Many chronic metabolic diseases are believed to begin in the gut, and long-term inflammation is thought to be a driving force.

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

Still, chronic inflammation is incredibly complex, and scientists are just beginning to explore how inflammation and diet may be connected.

It’s likely that the general healthfulness of your diet and lifestyle affects your risk of chronic inflammation and conditions linked to it, rather than a single dietary cause.

Thus, to keep yourself and your gut healthy, it’s best to focus on an overall healthy lifestyle with plenty of exercise, good sleep, and a diet based on real foods, plenty of prebiotic fiber, and few processed junk foods.