In a recent study published in Scientific Reports, researchers examined the role of specific gut microbes in the secretion of cytokines by peripheral blood mononuclear cells (PBMCs), monocyte-derived macrophages (MDM), and human colorectal adenocarcinoma cell line HT-29 cells and its contribution to the pathogenesis of asthma.
Study: The potential immunomodulatory role of the gut microbiota in the pathogenesis of asthma: an in vitro study. Image Credit: Rybalchenko Nadezhda/Shutterstock.com
Asthma is a highly prevalent lung disease that results in airway obstruction and chronic inflammation, generally manifesting as coughing, wheezing, tightness in the chest, and difficulty breathing. It affects over 200 million people worldwide and contributes substantially to the economic health burden.
The multifactorial process of asthma is associated with chronic inflammation of the airways that causes hyper-reactivity in the bronchioles. A genetic predisposition, environmental factors, diet, and viral infections during childhood are some major risk factors for asthma.
Increasing evidence shows that the gut microbiome plays a vital role in health and disease and is involved in fundamental processes of immune responses, defense against pathogens, nutrient absorption, and vitamin production.
Microbiological stimulation in the neonatal period is believed to play an important role in the maturation of gastrointestinal lymph tissue, the diversification of antibodies in the gastrointestinal tract, and immunoglobulin A production.
Given that gut microbiome dysbiosis in early childhood can have an impact on the maturation of the immune system, it is important to understand the role of specific gut microbes in the pathogenesis of asthma.
About the study
In the present study, the researchers examined the influence of lysates from Ruminococcus albus, Parabacteroides distasonis, Clostridium perfringens, and Bacteroides vulgatus on the secretion of selected cytokines by PBMCs, HT-29 cells, and MDMs.
Enzyme-linked immunosorbent assays (ELISA) were conducted to analyze the cytokine secretion after HT-29 cells, MDMs, and PBMCs were stimulated and incubated with lysates from R. albus, P. distasonis, C. perfringens, and B. vulgatus.
Previous studies have reported that fecal samples from neonates at high risk of developing asthma showed fewer strains of Faecalibacterium, Lachnospira, Rothia, and Veillonella.
Furthermore, newborns with an increased abundance of Bacteroides and Streptococcus species and a lower abundance of Ruminococcus gnavus and Bifidobacterium species in the fecal samples were at a higher risk of asthma and atopy.
Studies have also found that the gut's decreased abundance of Akkermansia, Bifidobacteria, and Faecalibacterium species predisposes children to a higher risk of asthma.
Given the evidence linking changes in gut microbial abundance to the risk of asthma, the researchers attempted to analyze whether lysates from R. albus, P. distasonis, C. perfringens, and B. vulgatus had an impact on the secretion of interleukins (IL) 1β, IL-10, IL-6, and tumor necrosis factor-alpha (TNF-α).
The bronchial hyperresponsiveness that occurs during asthma often has a changing pathogenetic basis. Chronic inflammation contributes significantly to bronchial hyperresponsiveness during the initial stages of asthma, while tissue remodeling in the airways is largely responsible in the later stages.
The bronchial structural cells release inflammatory mediators such as cytokines and chemokines required for inflammation amplification, and the epithelium in the bronchioles is actively involved in asthma pathogenesis.
Interactions with the infectious agent in asthma patients result in a decrease in interferon production by the bronchial epithelial cells, lowering the defense responses against these agents.
The findings from the present study showed that lysates from specific gut bacteria could modify the secretion of inflammatory mediators such as IL-10, IL-6, IL-1β, and TNF-α.
The results indicated that lysates from C. perfringens, and B. vulgatus significantly decreased the secretion of IL-1β by MDMs at doses of 400 micrograms. Additionally, the secretion of IL-6 by MDMs and PBMCs was significantly higher after the administration of lysates from P. distasonis and C. perfringens.
Lysates from P. distasonis, C. perfringens, and B. vulgatus at 100 micrograms were found to increase the secretion of IL-10 by PBMCs. In contrast, those from P. distasonis, C. perfringens, B. vulgatus, and R. albus brought about a similar increase in IL-10 secretion by MDMs.
Furthermore, lysates from B. vulgatus and P. distasonis were found to increase the secretion of TNF-α by MDMs and HT-29 cells.
Overall, the findings reported that lysates from R. albus, P. distasonis, C. perfringens, and B. vulgatus could increase the secretion of cytokines such as IL-10, IL-6, and TNF-α by PBMCs, HT-29 cells, and MDMs.
The modified secretion of pro-inflammatory cytokines through the action of these bacterial lysates could contribute to the pathogenesis of asthma.