The microbiome is the collection of microscopic organisms, also known as microorganisms, like bacteria, viruses, and fungi, that live in and on a particular organism. The human microbiome is composed of multiple sub-microbiomes, like the skin microbiome, the gut microbiome, and the vaginal microbiome. These microbiomes differ in environmental conditions, just like different areas on the globe differ in climate. Of particular interest to scientists is the gut microbiome because research has shown that the gut microbiome plays an important role in the overall health of a person. The gut microbiome not only affects intestinal health and metabolic function, but also affects the brain, heart, liver, and lungs [1]. Studies on the gut microbiome, and more generally the human microbiome, are still relatively new so much is still unknown. 

Scientists Taylor Young, Andrew Bray, and their colleagues set out to study the gut microbiome by looking at Klebsiella pneumoniae (abbreviated K. pneumoniae) infections in mice.  K. pneumoniae is a bacteria often transmitted in hospital settings and has become drug-resistant, making it a critical pathogen according to the World Health Organisation (WHO) [2]. Specifically the scientists were studying how the gut microbiome can protect its host against invading microorganisms, like K. pneumoniae, and how antibiotic treatment altered this protection.

This bacteria can cause pneumonia, bacterial infections in the blood, damage to the liver, and urinary tract infections. It often enters the body through the mouth and can take up residence in the gastrointestinal (GI) tract without causing symptoms. People with a healthy immune system may be unaware they carry the bacteria. In hospitals, however, many patients are immunocompromised, meaning they don’t have a fully functioning immune system. These patients are at high risk of experiencing severe disease from K. pneumoniae. In hospitals, outbreaks quickly spiral out of control. FRONTLINE reported on an outbreak of an antibiotic resistant strain of K. pneumoniae at the National Institutes of Health in Bethesda, Maryland. Explore their interactive timeline of the outbreak here [3]. By studying K. pneumoniae infections in mice, scientists can approximate what occurs during these outbreaks in a controlled manner. These studies may help prevent or stop future outbreaks with the potential to save many lives. 

The researchers began their project by determining that K. pneumoniae is able to colonize the GI tract of an individual mouse with a healthy microbiome. The researchers measured the amount of K. pneumoniae in the feces of the mice which tells them about the infection in the mouse and its ability to spread. The feces from the mice with healthy microbiomes were positive for K. pneumoniae for the entire duration of the experiment. The continuous presence of K. pneumoniae in the feces showed that the bacteria was able to live in the gut of these mice for an extended period of time. 

Another important aspect of the infection in the mice was that they were able to pass the K. pneumoniae to other mice in the same cage. This reflects the observation that humans are able to transmit the infection to one another in close proximity. The method of transmission used by K. pneumoniae is called fecal-oral transmission. In mice this occurs because they eat the feces of other mice. In humans it is hypothesized that fecal-oral transmission of pathogens occurs due to insufficient hand-washing and dirty surfaces transferring live pathogens. Many human pathogens and diseases like E. coli, giardia, and hepatitis A, spread through fecal-oral transmission. To learn more about fecal-oral transmission and how to prevent it, click here [4]. The researchers also confirmed that, like in many other pathogens, different strains of K. pneumoniae vary in their ability to colonize and cause disease in mice. Knowing the strain a mouse, or human, is exposed to is important for predicting the severity of infection. 

The key finding of this study came from investigating the effects of antibiotics on the gut microbiome. Scientists determined how much K. pneumoniae an ordinary mice released in their feces. Infected mice were then treated with the common antibiotic Streptomycin. This antibiotic does not kill K. pneumoniae but instead serves as a mechanism of disturbing the gut microbiome by killing microbes that normally live in a healthy gut. Antibiotic treatment triggered the mice to act as superspreaders, meaning they released pathogens, in this case in their feces, at a much higher dose than other infected individuals. Whether given a single dose or placed on continuous antibiotics, the mice remained superspreaders until three days after the antibiotic treatment finished. Repeated antibiotic treatments caused a spike in K. pneumoniae released for three days after each dose. 

The creation of superspreaders is critical to understand because they can pass the infection to many more new individuals than a non-superspreader. The researchers found support for this when they co-housed infected and uninfected mice. An uninfected mouse living with an infected mouse never treated with antibiotics had a 10-25% chance of developing an infection. An uninfected mouse living with an antibiotic treated mouse, a superspreader, had more than a 90% chance of becoming infected. 

These findings have significant implications in many different fields including epidemiology (the study of the spread of disease) and human medicine. There are still many things to learn and more experimentation is necessary to determine how scientists and doctors can collaborate to integrate these findings into improved patient treatments. One thing that can be predicted is that patients on antibiotics are more likely to be superspreaders and therefore extra precautions should be established to prevent them from interacting with immunocompromised individuals. 

References 

1. Gut Instinct: How the Gut Microbiome Influences the Body. In: Endocrine News [Internet]. 1 May 2015 [cited 17 Feb 2021].

Available: https://endocrinenews.endocrine.org/may-2015-gut-instinct/

2. WHO “priority pathogens” list: The most dangerous bacteria in the world. In: hygiene in practice [Internet]. [cited 1 Mar 2021].

Available: https://www.hygiene-in-practice.com/publication/who-priority-pathogens-list-the-most-dangerous-bacteria-in-the-world/

3. Rockwood B, Childress S. A Superbug Outbreak at NIH – Hunting the Nightmare Bacteria. In: FRONTLINE [Internet]. [cited 1 Mar 2021].

Available: http://www.pbs.org/wgbh/pages/frontline/health-science-technology/hunting-the-nightmare-bacteria/a-superbug-outbreak-at-nih/

4. Diarrheal Illness_Fecal-Oral Transmission and Prevention.2014.pdf.

Available: https://www.ok.gov/health2/documents/Diarrheal%20Illness_Fecal-Oral%20Transmission%20and%20Prevention.2014.pdf

Abby Wukitch (‘22) is a rising Senior at Bucknell University working towards a B.S. in Biology.

Abby is a Presidential Fellow working in Professor Moria Chambers’ lab since fall 2018. She studies the protective effect of chronic infection in Drosophila melanogaster on subsequent lethal infections. This summer she is continuing research through the Russo Fund for Undergraduate research in Biology and Chemical Sciences.

Abby is also the president of the Biology Club, participates in mentoring incoming Presidential Fellows, and leads outdoor activities such as hiking and camping through Bucknell Outdoor Education and Leadership (OEL). She also works as a lifeguard, a Teaching Assistant for multiple biology courses, and a facilitator for a ropes course at the Bucknell Challenge Course.

After Bucknell, Abby hopes to continue research in immunology and infectious disease. She plans to pursue a MD-PhD in order to continue research in a clinical setting.