This article is from WeChat public account: Return to Park ( ID: fanpu2019 ), compile: Xianjie, original title: “Be careful! “Friendly” probiotics may also become enemies “, picture from: Visual China

In 2014, in the intensive care unit of Boston Children’s Hospital, Dr. Greg Priebe was Treat a teenager with lung failure. To make matters worse, the patient was suffering from a high fever due to an infection brewing in the blood-this is caused by a bacterium called “lactobacillus”, which is commonly found in foods such as probiotic capsules and yogurt, This case reminded Priebe of a patient who had also been infected with lactobacillus after a back surgery a few years ago. Both patients were taking probiotics containing large amounts of lactobacilli at the time. This can’t help but make Priebe wonder whether the infection is caused by probiotics that are generally considered “friendly and harmless.”

Lactic acid bacteria Picture source: https://www.wbur.org/commonhealth/2019/11/22/probiotic-icu-infection-lactobacillus < / p>

Intensive care unit (ICU) Many patients, whether children or adults, take probiotics. Usually, patients take it at home to fight antibiotic-induced diarrhea. After entering the ICU, they will maintain this habit and take probiotics autonomously. In Canada, a large clinical trial (this trial involves multiple experimental centers) is testing whether probiotics can prevent Pneumonia caused by using a ventilator.

However, an article published in the journal (Nature Medicine) on November 7, 2019 by Boston Children’s Hospital Research in collaboration with the Israel Institute of Technology warns of the use of probiotics in the ICU. In a small number of cases, researchers found that the active bacteria in the probiotics could cause blood infections.

Investigative research on Investigating probiotic bacteremia

Lactobacillus is a common bacterium in probiotics. The Boston Children’s Hospital’s Infection Prevention and Control Team noted that bacteremia caused by lactobacillus occurred in ICU patients-between 2009 and 2014, 1.1% of patients with bacteremia in ICU had previously consumed probiotics. This incidence was of concern to Thomas Sandora, the medical director of infection prevention and control, and Kelly Flett, a pediatric infectious disease physician, so they decided to do a case-control study.

Sandora and Flett compared 6 ICU patients with bacteremia with 16 other ICU patients who took probiotics but did not develop bacteremia, and compared the two groups of patients according to the type of disease and the time they took probiotics. Make a match. Flett said they wanted to see if there were certain factors in the clinic that “can give suggestions for the use of probiotics in the ICU.”

However, the matching results do not give clear risk factors.

“We know from previous research that those patients with compromised immune systems or intestinal problems have probiotics that easily enter the bloodstream and have a higher risk of getting probiotics,” Sandora said, “but this time These patients do not have these risk factors, their only risk factor is: critical condition .

Genetic forensics forensics

So, the research entered the next stage-genomic research. Dr. Gregory Priebe and postdoc Christina Merakou collaborated with the Walter Reed Army Institute to use whole-genome sequencing technology to prove that bacteria in the blood of patients with ICU bacteremia and bacteria in probiotic capsules almost exactly match-the patient is infected with A strain called “Lactobacillus rhamnosus GG” (Lactobacillus rhamnosus GG, referred to as LGG, a type of Lactobacillus) .

Dr. Priebe explained that because many lactobacilli are normal flora of the gastrointestinal tract, other bacterial fingerprinting methods, such as pulsed-field gel electrophoresis, cannot provide a resolution high enough to ensure the authenticity of both strains Matches, so whole-genome sequencing must be used for high-level identification.

At the same timeThe hospital’s diagnostic laboratory for infectious diseases uses a research database on a MALDI-TOF mass spectrometer to match the results of bacterial identification of the patient’s blood isolate with the microorganisms in the probiotic capsule. The results prove that the laboratory identification results are consistent with the genome sequencing results.

(translation: matrix-assisted laser desorption ionization time-of-flight mass spectrometry, MALDI-TOF-MS, is a new type of soft ionized biological mass spectrometry, which can provide characteristics The fingerprints of microbial protein quality can be quickly identified by searching the database of characteristic mass spectral peaks or comparing with the mass spectral peaks of known microorganisms.)

Single-base resolution

The Boston Children’s Research team then collaborated with the Israel Institute of Technology to advance research to the next stage. They analyzed the bases in the bacterial DNA one by one to compare the single nucleotide polymorphisms of multiple LGG strains isolated from infected blood and probiotic capsules. (SNP) .

The hospital’s postdoc Merakou has been working on this project for three years. “No one has ever tested on a single base level,” she said. “We wanted to see if these bacteria had any new genetic mutations that made them more potent or better able to survive in the blood. “

With this technology, researchers can determine the source of these bacteria and infer the path they took from the capsule to the bloodstream, while also identifying their evolutionary direction in the host.

Evolving bacteria

In the end, researchers found changes in 11 genetic loci in the genome of bacteria isolated from blood. They also found that some LGG bacteria in probiotics once settled in the patient’s gastrointestinal tract A new mutation is created that makes it resistant to antibiotics.

“We have found a mutation that affects rifampicin. (an antibiotic) <"The exact site where bacteria bind," Merakou said. "Bacteria with this mutation develop resistance. "The experimental results also show that these bacteria are resistant to rifampicin, but not to other antibiotics.

The study also found that in different batches of probiotics, some mutations were apparently from LGG strains, but others were only present in bacteria isolated from the patient’s blood, suggesting that these mutations may allow bacteria to enter Blood or promote its survival in the blood .

The history of these bacteria is recorded in the genome-how they entered the bloodstream, what evolutionary selection pressures they came from, where they came from, and where they went. This is like an investigation process, most of the evidence comes from the cross-ratio of genomic data and clinical data of patients (such as the antibiotics they are receiving) Correct.

Benefits of Study takeaways

The above research results show that friendly bacteria not only become enemies, but also become a kind of super bacteria. Nonetheless, researchers emphasize that the risk of infection they find does not mean that probiotics are dangerous for everyone . Merakou said that the study only focused on critically ill patients in the children’s hospital, and that herself, as a Greek who “grew up yogurt from childhood,” “will not stop drinking yogurt because of our research, but we do need to Such things are more careful, if possible, even give parents some guidance. “

Based on research evidence, the research team suspects that these bacteria entered the blood from the gastrointestinal tract, but it is also possible that the

Gregory Priebe (left), Christina Merakou (center), and Thomas Sandora (right) in the Boston Children’s Hospital Intensive Care Unit

In general, in this study in the journal Nature Medicine, patients with ICU who used probiotics were 120 times more likely to be infected with lactobacillus than patients who did not take probiotics, but none of them died of the infection.

Other studies have shown the benefits of probiotics, especially for treating diarrhea caused by antibiotics.

Thus, a major international research project on the risks and benefits of taking probiotics in the ICU is currently underway, a randomized double-blind, placebo-controlled, high-standard clinical trial, “it will tell Can our risk of blood infection with probiotics be offset by other potential benefits of probiotics (such as preventing other types of infections) . “Priebe said .

At the same time, Patricia Hibberd, director of the Department of Global Health at the Boston University School of Public Health, said the study at the Children’s Hospital was not the first study to show the risk of probiotic infections, but it did provide a thorough understanding of the risks Researched. I see too much positive publicity about probiotics, so we need to convey the message to the public if they have the following conditions, such as weakened immune system function, intestinal problems and being in the intensive care unit , They should not take probiotics. She encourages patients with this type of problem to take the initiative to discuss it with their doctor, noting that doctors must better understand these risks. Moreover, she proposed that our understanding of probiotics-in favour or against-is still in its infancy, and further research is essential.

compilation source:


https://www.eurekalert.org/pub_releases/2019-11/bch-bpi111219.php < / span>

https://www.wbur.org/commonhealth/2019/11/22/probiotic-icu-infection-lactobacillus span>

https://www.nature.com/articles/s41591-019-0626- 9

This article is from the WeChat public account: Back to Park (ID: fanpu2019) , compile: Xianjie