The gut may be the ticket to reducing chemo's side effects

November 11, 2019

COLUMBUS, Ohio - In a new study, scientists observed several simultaneous reactions in mice given a common chemotherapy drug: Their gut bacteria and tissue changed, their blood and brains showed signs of inflammation, and their behaviors suggested they were fatigued and cognitively impaired.

The research is the first to show these combined events in the context of chemotherapy, and opens the door to the possibility that regulating gut bacteria could not only calm chemo side effects like nausea and diarrhea, but also potentially lessen the memory and concentration problems many cancer survivors report.

More research is needed to further understand how the chemo-modified gut influences the brain in a way that can have an impact on behavior. The same lab at The Ohio State University is continuing mouse studies to test the relationship and running a parallel clinical trial in breast cancer patients.

"This is the first time anyone has even looked to see if there's a link between the gut symptoms and the brain symptoms associated with chemotherapy," said lead author Leah Pyter, assistant professor of psychiatry and behavioral health and an investigator in the Institute for Behavioral Medicine Research at Ohio State. "There have been studies in humans that indicate that chemo alters microbes in the gut, and our study in mice had similar results.

"We were able to see that there are brain changes at the same time as the gut changes. We also looked at inflammation, and yes, there are all these changes happening at the same time. So there are correlations, and now we're looking into causality."

The study is published today (Nov. 11) in the journal Scientific Reports.

For this study, female mice received six injections of the chemotherapy drug paclitaxel and a control group of mice received placebo injections. Compared to the controls, the treated mice lost weight and showed signs of fatigue, and their performance on tests suggested they had memory loss.

The treated animals' guts, blood and brains were also affected in ways not seen in the control mice. The mix of bacteria in the gut microbiome changed, and the tissue lining the colon became abnormally extended. Specific proteins were present in circulating blood and the brain - along with activated immune cells in the brain - all indicating the immune system was busy producing a total-body inflammatory response.

The sequence of events suggested all these physiological changes were related: The gut was showing signs of permeability, meaning bits of bacteria could slip out of tight junctions in the intestine, an event that triggers an immune system attack. When the brain detects through the blood and neural signals that the body's immune system is activated, the brain responds in kind with its own inflammation. And brain inflammation is the culprit behind the "mental fog" symptoms known as chemo brain.

Pyter's team tested all the data for associations and found the strongest correlations between changes in the gut microbes and in the colon lining and the activation of immune cells called microglia in the brain.

"Every time chemo reduced bacteria in the gut, that reduction was correlated with these cells in the brain," said Pyter, also a member of the Cancer Control Research Program at Ohio State's Comprehensive Cancer Center.

"This suggests chemotherapy is affecting the microbes in the gut and affecting the lining of the gut, and both of those changes cause inflammation in the periphery, which creates signals that promote inflammation in the brain," she said. "That's how we get the brain involvement - through the immune system. And inflammation in the brain leads to sickness behaviors like fatigue and weight loss, as well as cognitive impairment."

Confirmation of these connections could lead to interventions for cancer patients - either dietary strategies such as probiotics or prebiotics or possibly fecal transplantation - to promote bacteria and conditions in the gut that protect the brain from inflammation, which should reduce chemo brain symptoms.

"This is just the first step of trying to broach the concept to see if these harsh gut effects of chemo have anything to do with chemo brain. It looks like it has potential," Pyter said.
-end-
This work was supported by The Ohio State University Wexner Medical Center and grants from the National Institutes of Health.

Kelley Jordan and Browning Haynes of Ohio State and Brett Loman and Michael Bailey of Nationwide Children's Hospital were study co-authors.

Contact: Leah Pyter, 614-293-3496; leah.pyter@osumc.edu

Written by Emily Caldwell, 614-292-8152; Caldwell.151@osu.edu

Ohio State University

Related Immune System Articles from Brightsurf:

How the immune system remembers viruses
For a person to acquire immunity to a disease, T cells must develop into memory cells after contact with the pathogen.

How does the immune system develop in the first days of life?
Researchers highlight the anti-inflammatory response taking place after birth and designed to shield the newborn from infection.

Memory training for the immune system
The immune system will memorize the pathogen after an infection and can therefore react promptly after reinfection with the same pathogen.

Immune system may have another job -- combatting depression
An inflammatory autoimmune response within the central nervous system similar to one linked to neurodegenerative diseases such as multiple sclerosis (MS) has also been found in the spinal fluid of healthy people, according to a new Yale-led study comparing immune system cells in the spinal fluid of MS patients and healthy subjects.

COVID-19: Immune system derails
Contrary to what has been generally assumed so far, a severe course of COVID-19 does not solely result in a strong immune reaction - rather, the immune response is caught in a continuous loop of activation and inhibition.

Immune cell steroids help tumours suppress the immune system, offering new drug targets
Tumours found to evade the immune system by telling immune cells to produce immunosuppressive steroids.

Immune system -- Knocked off balance
Instead of protecting us, the immune system can sometimes go awry, as in the case of autoimmune diseases and allergies.

Too much salt weakens the immune system
A high-salt diet is not only bad for one's blood pressure, but also for the immune system.

Parkinson's and the immune system
Mutations in the Parkin gene are a common cause of hereditary forms of Parkinson's disease.

How an immune system regulator shifts the balance of immune cells
Researchers have provided new insight on the role of cyclic AMP (cAMP) in regulating the immune response.

Read More: Immune System News and Immune System Current Events
Brightsurf.com is a participant in the Amazon Services LLC Associates Program, an affiliate advertising program designed to provide a means for sites to earn advertising fees by advertising and linking to Amazon.com.