Improving the health of the gut microbiome by way of fecal transplant (in mice) and dietary modification (in humans), has been shown by researchers to noticeably improve COPD symptoms. The finding could lead to microbiome-targeted treatments that provide relief to people suffering from this currently incurable condition.
Most often caused by long-term cigarette smoking, chronic obstructive pulmonary disease (COPD) is characterized by inflammation and emphysema, leading to progressive impairment of lung function. Globally, in 2020, COPD prevalence was estimated to be 10.6%, or 480 million cases. That number is expected to grow to 600 million cases by 2050.
Drug treatments have little effect in reversing COPD, slowing its progression, or preventing deaths attributed to the condition, and they have significant adverse side effects. However, researchers from Centenary Institute, the University of Technology Sydney, and the Hunter Medical Research Institute may have paved the way for new therapeutic treatments for COPD by finding that the gut microbiome plays a pivotal role in the disease’s development.
“The gut hosts the largest and most diverse microbiome in the body that, depending on its composition, can either trigger or inhibit inflammation, including in the lung,” said Phil Hansbro, corresponding author of the study. “We were able to identify specific gut bacteria associated with the development of COPD in our mouse models, confirming the complex interplay between the gastrointestinal microbiome, inflammation, and lung disease.”
The transfer of whole microbial communities from healthy individuals via fecal microbial transfer (FMT) is an effective treatment for patients with colitis caused by Clostridioides difficile bacteria, but whether it works for other diseases has not been as well-researched. So, the researchers decided to test it out.
Mice first had their microbiome normalized before being exposed to room air or cigarette smoke for 12 weeks to model COPD, with a subset of these mice exposed for only eight weeks to model smoking cessation. Air-exposed mice then received FMT from cigarette-smoke-exposed donors and vice versa.
All experimental groups showed a shift in microbiome composition between weeks zero and 12, with increased microbial diversity. However, particular bacterial species changed significantly between groups, some enriched and others depleted. The researchers could correlate lung and gut pathology with individual species.
Following FMT, mice exposed to cigarette smoke or smoking cessation model mice had significantly lower numbers of immune cells in their lung tissues and significantly less lung inflammation. The combination of smoking cessation and FMT had an additive effect, further reducing immune cells and lung inflammation. Importantly, FMT alleviated both emphysema and impaired lung function after cigarette smoking for 12 weeks.
“We used FMT to transfer beneficial gut microorganisms between healthy and COPD mice, that helped to reduce lung inflammation and improve breathing,” Hansbro said. “This suggests a potential therapeutic effect of these specific gut microbes in mitigating COPD-related issues.”
The researchers next assessed whether dietary supplementation with complex carbohydrates improved COPD outcomes. Mice were exposed to cigarette smoke for eight weeks and fed either a control diet or an equivalent diet with all carbohydrates as resistant starch. Because resistant starch is not digested by the host, it provides food to the ‘good bacteria’ of the microbiome. The starchy diet alleviated cigarette-smoke-induced airway inflammation, consistent with the protective effects of FMT.
To explore whether these findings translated to humans, the researchers conducted a small study of 16 patients with COPD. One group was fed supplements of inulin, a common fermentable fiber, for four weeks, while another was fed a placebo. The inulin group reported fewer episodes of worsening or respiratory symptoms requiring additional pharmaceutical intervention than the placebo group and improved health-related quality of life. Analysis showed that microbiome composition was significantly different after inulin consumption.
“Enhancing the diet of a small select group of human COPD patients through dietary fiber supplementation led to noticeable improvements in disease symptoms,” said Kurtis Budden, the study’s lead author. “Likewise, providing a high-resistant starch diet to mice with COPD yielded beneficial outcomes. These discoveries point towards a promising direction for dietary modification in the management of COPD.”
The findings pave the way for developing microbiome-targeting treatments that could provide relief to people with COPD, a condition for which there is currently no cure.
The study was published in the journal Gut.
Source: Centenary Institute
