Probiotics improve strength and functional capacity in patients with COPD, based on a randomized, placebo-controlled trial.
The improvements stem from decreased gut permeability, which reduces circulating inflammatory cytokines, leading to stabilization of neuromuscular junctions, reported lead author Asima Karim, MBBS, PhD, of the University of Sharjah, United Arab Emirates, and colleagues.
“The manipulation of gut bacteria with probiotics may be an attractive therapeutic strategy to strengthen the intestinal barrier,” the investigators write in Archives of Gerontology and Geriatrics. “Probiotic supplements reduce the pathological translocation of bacterial metabolites and ameliorate the systemic inflammatory state in multiple diseases.”
In COPD, both intestinal permeability and systemic inflammation have been linked with sarcopenia, suggesting a common, yet unexplored thread, according to Karim and colleagues. “To our knowledge, no previous study has investigated the effects of probiotics on sarcopenia in COPD patients,” they write. “However, probiotics are shown to reduce lung inflammation and improve airway remodeling in experimental animal models of COPD.”
Their trial enrolled 104 men with COPD between 63-73 years of age. Patients were randomly assigned in 1:1 ratio to receive either placebo or a probiotic containing 112 billion live bacteria, including one strain of Streptococcus, three strains of Bifidobacterium, and four strains of Lactobacillus.
At baseline and 16 weeks, the investigators measured handgrip strength, short physical performance battery (SPPB), gait speed, and appendicular skeletal mass index. In conjunction, six plasma biomarkers characterized intestinal permeability (zonulin, claudin-3), neuromuscular junction degradation (CAF22), systemic inflammation (CRP, creatine kinase), and oxidative stress (8-isoprostanes).
Clinically, probiotic treatment was associated with significant improvements in handgrip strength, gait speed, and functional capacity (SPPB). Concurrently, patients in the probiotic group had significant improvements in gut permeability (zonulin, claudin-3), neuromuscular junction degradation (CAF22), systemic inflammation (CRP), and oxidative stress (8-isoprostanes). In contrast, patients in the placebo group showed no significant changes in clinical picture or biomarkers, apart from zonulin, which increased over time, suggesting worsened gut permeability. Creatine kinase, a measure of systemic inflammation, showed no change in either group.
“Our primary finding is that probiotics can improve muscle strength and functional capacity in COPD patients,” Karim and colleagues conclude. “These effects are at least partly mediated by reduced gut leakage and associated reduction in systemic oxidative stress and chronic inflammation. Additionally, plasma zonulin, claudin-3, and CAF22 may be useful to evaluate the indexes of sarcopenia and functional dependency.”
In a written comment, principal author Rizwan Qaisar, MBBS, PhD, also from the University of Sharjah, pointed out that “probiotics have a high safety profile and adverse effects are rare,” so “most patients with COPD can take probiotic pills.”
Whether they will see improvements like those in the clinical trial, however, is uncertain. Yvonne Huang, MD, of the University of Michigan, Ann Arbor, said that the benefits of probiotics for patients with COPD and moderate to severe sarcopenia “likely will vary between patients.”
“Currently there is no good way to predict which patients are most likely to have sustained medical benefit from probiotic supplements,” Huang said in a written comment. “Moreover, probiotic products vary in formulation and standardization, such that bacterial strains and their viability across products might vary. Lastly, patient-specific factors also likely play a role in therapeutic response. [These are] aspects that still need to be better understood.”
Qaisar agreed that more work is needed. “It is not known exactly which bacteria colonize the gut of COPD patients following probiotics use,” he said. “How they cross-talk with muscle and other organs is also not well known. Further research should investigate the amount and types of bacteria, and what molecules they release in blood to improve muscles and other organs.”
Huang, whose research focuses on microbiome-host interactions in COPD and asthma, suggested that bacteria outside the gut may also be driving clinical outcomes.
“There is growing interest in understanding the role of the lung microbiome in COPD pathogenesis,” Huang said. “The lungs are more difficult to access, and this makes the lung microbiome somewhat harder to study. However, there has been recent headway and it would be of interest to understand better the relative contributions of lung vs gut microbiome to COPD pathogenesis, and whether the microbiome plays a greater role in shaping certain phenotypes of COPD.”
The investigators and Huang reported no relevant financial relationships.
Arch Gerontol Geriatr. Published online May 10, 2022. Abstract
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