Clinical trial of a probiotic and herbal supplement for lung health.

Introduction: Dysbiosis of the gut microbiome may augment lung disease via the gut-lung axis. Proteobacteria may contribute to tissue proteolysis followed by neutrophil recruitment, lung tissue injury, and perpetuation of chronic inflammation. To study the effects of probiotics across the gut-lung axis, we sought to determine if a Lactobacillus probiotic and herbal blend was safe and well-tolerated in healthy volunteers and asthmatic patients. Methods: We conducted a 1-month randomized, open-label clinical trial in Cork, Ireland with healthy and asthmatic patients who took the blend twice a day. The primary endpoint was safety with exploratory endpoints including quality of life, lung function, gut microbiome ecology, and inflammatory biomarkers. Results: All subjects tolerated the blend without adverse events. Asthmatic subjects who took the blend showed significant improvements in lung function as measured by forced expiratory volume and serum short chain fatty acid levels from baseline to Week 4. The gut microbiome of asthmatic subjects differed significantly from controls, with the most prominent difference in the relative abundance of the proteobacteria Escherichia coli. Administration of the probiotic maintained overall microbial community architecture with the only significant difference being an increase in absolute abundance of the probiotic strains measured by strain-specific PCR. Conclusion: This study supports the safety and efficacy potential of a Lactobacillus probiotic plus herbal blend to act on the gut-lung axis. However, due to the lack of a control group, a longer blinded, placebo-controlled study will be warranted to confirm the efficacy improvements observed in this trial. Clinical trial registration: https://clinicaltrials.gov/, identifier NCT05173168.

Microbial-induced Redox Imbalance in the Neonatal Lung Is Ameliorated by Live Biotherapeutics.

Bronchopulmonary dysplasia (BPD) is a common lung disease of premature infants. Hyperoxia exposure and microbial dysbiosis are contributors to BPD development. However, the mechanisms linking pulmonary microbial dysbiosis to worsening lung injury are unknown. Nrf2 (nuclear factor erythroid 2-related factor 2) is a transcription factor that regulates oxidative stress responses and modulates hyperoxia-induced lung injury. We hypothesized that airway dysbiosis would attenuate Nrf2-dependent antioxidant function, resulting in a more severe phenotype of BPD. Here, we show that preterm infants with a Gammaproteobacteria-predominant dysbiosis have increased endotoxin in tracheal aspirates, and mice monocolonized with the representative Gammaproteobacteria Escherichia coli show increased tissue damage compared with germ-free (GF) control mice. Furthermore, we show Nrf2-deficient mice have worse lung structure and function after exposure to hyperoxia when the airway microbiome is augmented with E. coli. To confirm the disease-initiating potential of airway dysbiosis, we developed a novel humanized mouse model by colonizing GF mice with tracheal aspirates from human infants with or without severe BPD, producing gnotobiotic mice with BPD-associated and non-BPD-associated lung microbiomes. After hyperoxia exposure, BPD-associated mice demonstrated a more severe BPD phenotype and increased expression of Nrf2-regulated genes, compared with GF and non-BPD-associated mice. Furthermore, augmenting Nrf2-mediated antioxidant activity by supporting colonization with Lactobacillus species improved dysbiotic-augmented lung injury. Our results demonstrate that a lack of protective pulmonary microbiome signature attenuates an Nrf2-mediated antioxidant response, which is augmented by a respiratory probiotic blend. We anticipate antioxidant pathways will be major targets of future microbiome-based therapeutics for respiratory disease.

Efficacy of a Probiotic and Herbal Supplement in Models of Lung Inflammation.

BACKGROUND: Gut microbiome dysbiosis is associated with lung disease through the gut-lung axis. Abundant proteobacteria increase MMP-9 and contribute to tissue proteolysis followed by neutrophil recruitment, lung tissue injury, and perpetuation of chronic lung disease. We sought to determine if a scientifically formulated probiotic and herbal supplement could attenuate neutrophilic inflammation and improve lung structure and function in models of lung inflammation. METHODS: For in vitro experiments, epithelial cells exposed to proteobacteria were treated with resB-a blend of three probiotic Lactobacillus strains and turmeric, holy basil, and vasaka herbal extracts. For in vivo experimentation, mice exposed to pulmonary proteobacteria-derived lipopolysaccharide were treated by gavage with resB. RESULTS: In vitro, the bacterial and herbal components of resB decreased activity of the MMP-9 pathway. Mice exposed to LPS and pre- and post-treated with resB had decreased neutrophil recruitment and inflammatory biomarkers in bronchoalveolar lavage fluid, serum, and lung tissue compared to untreated mice. CONCLUSIONS: This study describes the mechanisms and efficacy of probiotic and herbal blend in pre-clinical models of lung injury and inflammation.

Portal vein thrombosis as a thrombotic complication of COVID-19 mRNA vaccine: A case report and literature review.

Thrombosis following COVID-19 vaccination commonly occurs with vector-based vaccines. The proposed mechanism is vaccine-induced thrombotic thrombocytopenia (VITT), with thrombocytopenia as principal manifestation. We present a 51-year-old male who came with isolated portal vein thrombosis (PVT) one day after Moderna vaccination, without associated thrombocytopenia, challenging VITT as being the only patho-mechanism. Further exploration of these possible alternative mechanisms is needed for COVID-19 vaccine-related thrombotic complications.