Take a lot of medicine, but no effect?

As we all know, the intestinal microbiome known as the "second brain" of humans contains hundreds of different kinds of bacterial communities, which are closely related to human health and diseases, such as obesity, cardiovascular disease, type 2 diabetes, and cancer.
, And mental illnesses such as depression and Alzheimer’s
.

Previously, a large number of studies have confirmed that the composition of intestinal flora varies from person to person, and that healthy people have a large degree of similarity; unhealthy people show great differences in bacterial composition
.

When the balance between the pro-inflammatory response that triggers the disease and the anti-inflammatory response that fights the disease in the intestine is broken, people will get sick, and it is natural to take medicine to get sick
.

However, why do some people not take less medicine but can’t wait for the effect of the medicine? In a new study published in Nature on September 9, Beijing time, a research team led by the European Molecular Biology Laboratory (EMBL) and the Medical Research Council (MRC) of the University of Cambridge in the UK partially answered this doubt.
: Due to individual differences in the composition of the intestinal flora, some common drugs accumulate in the bacteria, and indirectly change the function and composition of the bacteria, which may directly affect the effectiveness and side effects of the drugs
.

In other words, the bacteria “privately hide” the drug without chemical modification, thereby reducing the availability of the drug to the body
.

Early studies have shown that bacteria can chemically modify certain drugs.
This process is called biotransformation, which is considered to be the main way bacteria affect the availability of drugs
.

The interaction between drugs and bacteria can reduce the adaptability of bacteria, or change the availability of drugs through biotransformation, and this will have a positive or negative impact on the activity and efficacy of drugs
.

In this new study, in order to expand the understanding of the effects of bacteria on drugs, the researchers systematically analyzed the interaction of 15 common human targeted drugs (12 oral small molecule drugs) with 25 representative strains of human gut bacteria
.

These drugs include anti-inflammatory drugs, antidepressants, and diabetes drugs, which can have different effects on individuals, including side effects such as intestinal problems and weight gain
.

The researchers tested how each drug interacts with selected bacterial strains.
A total of 375 bacteria-drug tests were performed, and 70 bacteria-drug interactions were discovered, 29 of which are completely unknown
.

Among these 29 new interactions, 17 drugs have accumulated inside the bacteria without chemical modification
.

The researchers said that due to the different composition of the intestinal flora, there are great differences between individuals
.

But in this experiment, they even saw the difference between different strains of the same bacteria
.

Researchers have found that the antidepressant duloxetine and the antidiabetic drug rosiglitazone bioaccumulate in bacteria (bioaccumulation, also known as bioaccumulation); the asthma drug montelukast and the chronic obstructive pulmonary drug roflumilast Both drugs are bioaccumulated by some bacteria and chemically modified by others
.

They also found that the bioaccumulation of drugs changed the metabolism of bacteria
.

For example, the antidepressant drug duloxetine binds to several metabolic enzymes in bacteria and changes the metabolites they secrete
.

The researchers then cultivated a small colony with 5 common intestinal bacteria and found that duloxetine not only significantly changed the balance of the flora, but also changed the molecules produced by the bacteria that accumulate drugs, and other bacteria feed on these bacteria
.

As a result, the bacteria that consume the drug grow more, causing an imbalance in the composition of the flora
.

Next, the researchers used Caenorhabditis elegans as a model system to study the effects of the bioaccumulation of duloxetine on the host response
.

The results show that duloxetine also accumulates in some bacteria
.

In contrast to nematodes that grew with bacteria that did not accumulate duloxetine, the behavior of the nematodes changed after exposure to duloxetine
.

This is consistent with the results previously observed
.

In summary, the study found that due to the bioaccumulation of intestinal bacteria, the therapeutic effect of host-targeted drugs can be adjusted in two ways: one is by reducing the main effect of drug availability; the other is by changing metabolites.
The secondary effect of secretion, the latter can lead to changes in the composition of the flora, which is closely related to the ineffectiveness or side effects of some drugs
.

The researchers stated that it is necessary to further study the gut bacteria-drug-host interaction in other model systems or clinical settings
.

Link to the paper: https:// Hot Article Selection in 2020 1.
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