The reproducibility of animal experiment results is poor, and bacteria cannot escape their responsibility

  Laura McCabe, a physiologist at Michigan State University, is studying a drug that affects bone density. In the first experiment, her team found that the drug can reduce bone density. She was very happy. To further confirm the result, they verified it. In order to ensure the reproducibility of the experiment, mice of the same species were purchased from the same company, placed in cages in the same animal room, and fed the same diet. However, the result of the second experiment was completely opposite to that of the first experiment. The bone density of the animals in the treatment group increased without decreasing.

  Maybe McCabe thought it was an accident. So I did the third experiment, but it didn't work this time. Faced with three completely different experimental results, she became very confused. Due to the presence of signals in the intestine that may affect bone formation and absorption, her team found in the intestine the reason for determining the types of microorganisms in the stool samples of three experimental animals. Hope to analyze and get unexpected results. Each experimental animal has a different microbial composition. McCabe does not know why the intestinal flora of these animals has changed. It could be because of the box containing the animal, or because of the technician's clothing. But in any case, these bacteria will affect the effectiveness of the drug for a reason. More and more evidence shows that the differences in the distribution of bacteria, viruses, fungi, protozoa and archaea in the intestines are also important reasons why many experiments cannot be repeated. A few years ago, the factors of intestinal flora were rarely considered, but these factors are now receiving more and more attention. Veterinarian Claire Hankenson (Claire Hankenson) said at a recent laboratory animal health conference: "I don't know how to identify." Mouse gut microbes are often variable, difficult to measure, and almost impossible to standardize. Simply removing bacteria is not only very difficult, it is also not a good idea. This is because intestinal bacteria themselves are an important factor in maintaining animal health and immune function. Some scientists even wonder whether it is possible to control the stability of animal intestinal flora. The results of animal studies and human clinical studies have shown that gut microbes affect the susceptibility of many diseases (such as AIDS and asthma) and are a key factor affecting obesity and drug influence.

  A 10-year Pfizer study found that the relative concentration of certain food metabolites in the urine of rats showed abnormal changes, and this is precisely an important indicator of drug testing. The researchers strictly controlled the animals for several weeks, and finally stabilized the changes in metabolites. No flora analysis was performed, but we suspect that these changes are caused by the intestinal flora. In the process of a mouse model study of multiple sclerosis at the University of Missouri in 2015, adding common antibiotics to animal drinking water can reverse the symptoms of animal diseases. Putting these animals together with other flora-rich animals can cure the symptoms of the disease. This indicates that the manifestation of animal diseases depends on the specific balance of intestinal flora. Craig Franklin and Aaron Ericsson, veterinary pathologists at the University of Missouri, are preparing to analyze the bacterial species of this phenomenon. Five years ago, only a few specialized laboratories were able to perform flora analysis, but now it has become routine to perform bacterial sequencing on various samples.

  In 2015, they defined the normal flora of laboratory mice for the first time. The fecal flora of these animals and many mammals consists of two types of flora. Vegetarian food is closely related to Bacteroides. However, the diversity of the flora varies from supplier to supplier. For example, the supplier mouse lacks the important bacterial segmented filamentous fungus SFB. This can help mice produce antibiotics and immune cells in the intestine. The diversity of bacteria is closely related to the health of animals. Recent studies have shown that poor hygiene may lead to death and death of certain animals, or make them healthy. display. David Massopast, an immunologist at the University of Minnesota, did just that and caught a mouse from the barn of the petting zoo. Masopasto suspects that commercial laboratory mice do not fit the characteristics of human life. Keep these animals under strict purification conditions. Humans do not live in a sterile environment, so using these animals to simulate human diseases or conditions may not be appropriate.

  Mssopaste and colleagues showed in the April 2016 “Nature” paper that wild mice and mice purchased from pet stores are stronger than laboratory animals, have more complex immune systems, and are closer to adult animals. Raising experimental mice with these dirty mice can make the immune system of experimental mice stronger and closer to humans.