Impacts of a damage microbiome - overview

In many ways, we are more microbes than humans.

Our cells are outnumbered by the microbes (including bacteria, fungi and viruses) by a factor of 1.3 to 1 and their genes even outnumber the genes of the human body by a factor of 150:1! These genes are important tools for our bodies, without which we wouldn't feel so good, or in fact, without which we wouldn't be able to survive.

Until recently we have been treating this huge population of bacteria — which lives with us in a tight symbiosis (mutual beneficial cooperation)— like an enemy, without realizing that we harm our very own bodies by doing so.

Our bodies resemble as diverse ecosystems as planets, with each body site harboring a specific ecological community with specific tools. A perturbation of one of these communities, also called dysbiosis, makes us feel very sick – and we are only just beginning to discover just how devastating that is.

Antibiotics destroy complete ecosystems
Antibiotics destroy complete ecosystems

Antibiotics function like a nuclear bomb

Over the last 70 years antibiotics saved millions of lives. Today, in life threatening situations, like sepsis, or a severe lung infection antibiotics must be employed. But we should be aware that it comes at great expense and that therefore antibiotics should not be regarded as a casual drug.

Antibiotics are the biggest threat to our microbiome. They are not precise weapons, rather they function like a nuclear bomb, which destroys entire eco-systems. In the many decades since they have become widely used, they’ve left a clear path of destruction. An increase in diabetes type I and asthma patients also seems to be correlated to the excessive use of antibiotics.

The dysbiosis impacts our whole body.

By removing our beneficial bacteria, it makes us vulnerable to pathogenic bacteria, which move in on a wiped-out ecosystem where they can then settle and make us sick. However, the microbiome of healthy people eventually recovers within a year, but immune-deficient people struggle to regain their healthy microbiome, which results in a vicious circle of the need for more antibiotics to be taken…

Besides the vulnerably towards pathogens, there are various diseases which correlate with the removement of our beneficial bacteria.

Digestive System

Diseases of the digestive system
Diseases of the digestive system

Diarrhea

A very well-known case of an imbalanced ecosystem in our bodies is the antibiotics-associated diarrhea. First, the gut’s ecosystem is impaired by the unspecific antibiotics and thus the gut loses many important tools it needs for healthy digestion, along with the necessary weapons to fight pathogenic bacteria. The exposed areas which crop up on the intestinal walls are now the perfect place for pathogenic bacteria to colonize. One of the most abundant and dangerous ones is called Clostridium difficile. C. difficile damages the mucosa and induces inflammation of the colon through the release of two potent toxins.

Cover from Fatboy Slim - click for more information
Cover from Fatboy Slim - click for more information

Obesity

The microbial composition of our gut influences our appetite and the ability to deposit fat.

The bacteria residing in our stomach, namely Helicobacter pylori, tell us when we´re hungry or full. Besides regulating the acidity in the stomach, this bug causes a decrease in the hormone ghrelin, which is involved in appetite regulation. The absence of this bacterium in the stomach causes elevated ghrelin secretion, leading to an even bigger appetite. Unfortunately, H. pylori has had a bad reputation throughout the last decades as a causative agent for peptic ulcers in susceptible people; it has therefore almost been eradicated from our stomachs through the use of antibiotics. For example, two or three generations ago in the U.S., 80%  of Americans harbored this bug; now less than 6% of American children are host to it, which may be one explanation for the increase in child obesity in the United States. At the same time, a formerly very rare form of oesophagus cancer increased ten-fold.

The composition of our microbiota in the intestines determine the amount of calories we can use from the food we eat. In former times, when food was a scarce good, people with a microbiome that was able to deposit more fat from the food had a greater chance of survival. Now that food is available at any time, these microbiomes induce obesity. Two people eating the same amount of food can either become obese or stay slim, depending on how their microbiomes utilize the carbohydrate source.

On the other hand, the kind of food we eat also influences the gut microbiome. When looking at people living in countries such as Japan, where more plant-derived carbohydrates are consumed, we find more bacteria capable of breaking down these plant carbohydrates in the gut. Also, the consumption of high-fat products reduces the total volume of the intestinal microbiome volume and induces the growth of bacteria that support a rapid fat deposition.

Heterocyclic amines, present in grilled meat can result in cancer.
Heterocyclic amines, present in grilled meat can result in cancer.

Gastrointestinal cancers

Your microbiome can also correlate with gastrointestinal cancers. It's not your microbiome which is inducing the cancer, it is the food you eat that induces the wrong bacteria to feel at home in your intestines. The Western-style diet in particular (a great deal of meat and fat coupled with a low intake of vegetables) favors the bacteria that produce specific enzymes and bile acids. These special enzymes can turn harmless compounds into carcinogens, such as heterocyclic amines, which you eat with grilled meat. After having transformed them into an electrophilic derivative, it can damage your DNA and thus result in cancer. So, an apple a day…

Inflammatory bowel disease

One disease which shows how dependent bacterial species are on one another is inflammatory bowel disease (IBD). IBD is a chronic, relapsing inflammation of the gastrointestinal (GI) tract, leading to mucosal damage. Normally in healthy individuals the GI tract is dominated by microbes of the divisions Firmicutes and Bacteroides. In IBD patients these bacteria are not dominant. The lowered number of Firmicutes in turn leads to a reduced abundance of Clostridium (of the IXa and IV groups), which normally lowers the level of pro-inflammatory cytokines by the release of butyrate. Additionally, the bacterium Bacteroides fragilis which is also reduced in IBD patients, boosts regulatory T cells, and thus stops the pro-inflammatory T cells from becoming too aggressive. Taken together, bacteria which are usually there to keep the immune system in check, are missing, thus the immune system is hyperactive and reacts against its own cells.

Skin

Skin Diseases
A damaged microbiome can cause skin diseases

Atopic Dermatitis

Also known as Neurodermatitis, atopic dermatitis (AD) mostly affects children and is a very unpleasant chronic infection of the skin. A dramatic dysbiosis plays a role in this disease. The question is, what came first: the inflammation of the skin or the infection with Staphylococcus aureus? A dramatic overabundance of S. aureus (90%) on affected but also on unaffected skin of AD patients may lead to the conclusion that latter is correct. In healthy individuals, S. aureus is very rarely found on the skin. The dominant S. aureus in AD patients monopolizes the space and nutrients of all the other good commensals which would in fact eventually kill this bug. Interestingly S. epidermidis is also found more often in AD patients than in healthy persons, suggesting that S. epidermidis recruited its army to fight against S. aureus, but this still is only an assumption.

The bacterium which tortures us with acne is Cutibacterium acnes
The bacterium which tortures us with acne is Cutibacterium acnes

Acne

Many of us know this skin disease from puberty – and we were not alone; 85% of teenagers are affected by acne. The bacterium which tortures us during our teens is Cutibacterium acnes, which formerly lived with us in peaceful symbiosis. With the onset of puberty, the chemical composition of the skin, primarily in the face, undergoes changes due to the hormonal shift. These changes cause a battle between the immune system and the Cutibacterium, leading to infected sebaceous glands and thus acne. Scientist must further investigate whether there is a special C. acnes species that is responsible for acne that differs from our commensal friends… we're especially excited for new findings here!

Immune System

A dysbiosis may result in allergies.
A dysbiosis may result in allergies

The microbiome has one very important mission in our body: to train our immune system. Many autoimmune diseases are the result of a disturbance to the adaptive immune system. Since autoimmune diseases like type I diabetes, rheumatoid arthritis or asthma are increasing, some speculate that changes in the body’s environment could be to blame. Environmental factors like unbalanced diets, the widespread use of antibiotics and other social factors like caesarean birth, the omnipresence of disinfectants, or fewer siblings have reduced the diversity of our microbiome. The result is a dysbiosis, an imbalance of the microbial communities on and in our bodies, thus our immune system trainers’ loss of control. Our immune system doesn´t know how to distinguish the good from the bad cells and begins to attack our own body, expressed through autoimmune diseases or allergies.

Nervous System

Your gut influences your feelings
Your gut influences your feelings and your brain controls your gut

Do you go with your gut feeling? Actually, this old proverb harbors more truth than you think. Your gut influences your feelings and your brain controls your gut through the gut-brain axis. A big part of this communication involves your microbiome. The most important link between the gut and the brain is the vagus-nerve. It controls salivation, the heartbeat and digestion. Vice versa, the gut tells the brain “I am full and I feel good”, or a calm heartbeat signals that you are relaxed… The messages this nerve receives come from the metabolites of your gut microflora and from messenger substances in your gut immune- and hormone-cells. The messenger substances from your gut immune- and hormone-cells are in turn dependent on your gut microbiome. Another route to the brain is via the blood, through which hundreds of thousands of bacterial metabolites travel your body.

Experiments with mice have proven the connection between the gut microbes and the brain. A transfer of gut bacteria from docile mice to anxious mice made the anxious mice fearless. The first trials with humans are currently underway. So far, the administration of yoghurt and probiotics have shown a positive influence on one’s mood. If all these indications are taken together, one could imagine that, in the future, psychiatrists will first screen their patients suffering from depression for their gut microbes in order to feed the good microbes which are missing. Until then, eat healthy!

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