clinical_frontiers revision_clean 050923

Lactobacillus administration and immune regulation of Th1/Th2 response, reducing allergic 283 inflammation characteristic of asthma (14, 34). The effect of the herbal extracts can also not be 284 discounted, as turmeric, holy basil, and vasaka have antioxidant and anti-inflammatory properties 285 (22, 35). Although FVC values were not statistically significant, a longer study with more subjects 286 may reveal a larger impact over time. 287 As anticipated, the probiotic induced no significant alterations in the global gut microbiome 288 community composition of the human participants (36). This agrees with prior literature that 289 demonstrates a limited long-term alteration in the gut microbiota from probiotics in healthy adults, 290 that stems from colonization resistance from the microbiota and host factors that perform ecology 291 maintenance (36-40). Alternatively, prior studies of probiotic administration have suggested that the 292 administration of a Lactobacillus probiotic can alter the prevalence of other Lactobacillus strains 293 without altering overall community structure (36). We verified by strain-specific PCR that the three 294 Lactobacillus strains contained in the probiotic blend increased from baseline to Week 4, of note 295 significantly in the asthmatic population. 296 We identified robust differences in the microbiota of asthmatic patients in our cohort, confirming 297 prior observations that community composition was associated with altered microbiota (41, 42). 298 Specifically, an increase in proteobacteria E. coli was particularly notable, since proteobacteria have 299 been linked with increased risk of respiratory disease (43). These differences are interesting and 300 deserving of further validation in a larger cohort of asthmatic individuals. 301 There are several limitations to this study, as its primary focus was safety. The study was unblinded 302 and did not have a placebo group. It is difficult to credit the observed improvements to specific 303 components of the blend. We also did not collect efficacy data at Week 2 (Visit 3), although it is 304 unlikely that an effect would have been observed after two weeks. The magnitude of change in 305 SCFAs required to affect biomarkers is unknown, as we did not assess asthma-specific markers of 306 inflammation in serum such as eosinophils, leukotrienes, or IL-5. Future trials will include a placebo 307 arm and a longer administration period in order to be able to draw stronger conclusions about clinical 308 efficacy endpoints. 309 Information on the type or severity of asthma was not collected. If a participant had intermittent or 310 non-seasonal asthma, their resolution of symptoms or improvement in lung function could have been 311 reflective of the regular course of the disease. In regard to allergic asthma, three of the asthmatic 312 participants reported having allergic rhinitis; however, none reported allergic symptoms during the 313 trial. If a participant did have an allergic asthma attack, it could have skewed the SGRQ or lung 314 function results, providing either a false improvement or false worsening result. However, due to the 315 season in which the trial was conducted, a seasonal attack was less likely. The study was conducted 316 in its entirety between November 23, 2021, and January 20, 2022, a time of the year during which 317 seasonal allergies are rare and do not begin until mid-late January in Ireland. 318 In summary, the Lactobacillus probiotic and herbal blend was found to be safe in healthy and 319 asthmatic subjects, and improvements in lung function were accompanied by potentially beneficial 320 increases in SCFA in asthmatic subjects. Based on the results of this preliminary clinical study, we 321 propose that this blend may improve lung function and inflammation by supplementing microbes in 322 the gut to increase SCFA production in systemic circulation. Clinical relevance of these findings 323 affects both patients with and without existing respiratory conditions who are seeking a means to 324 support their lung health. 325

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This is a provisional file, not the final typeset article

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