D94-10 I Gut a Feeling: Microbiome of the Firehouse Randomized Clinical Trial

Rationale

Dietary interventions can alter the gut microbiome influencing pulmonary function, metabolic pathways, and physiological health. We identified associations between dietary-induced microbiome changes and health outcomes in a cohort with high exposure to particulate matter.

Methods

Food Intake Restriction for Health Outcome Support and Education(FIREHOUSE) is a six-month randomized, controlled(RCT), parallel, unblinded, exploratory multi-disciplinary dietary intervention. FDNY firefighters with World Trade Center-Lung Injury(WTC-LI) were enrolled in a nutritional intervention and had gut microbiome sequenced pre/post low-calorie Mediterranean diet(LoCalMed), Clinicaltrials.gov:NCT03581006.

Microbiome: In a pilot subset, stool samples were collected(Omnigene-Gut, DNA-Genotek) at baseline and 6-month follow-up (N = 20 Usual Care (UC), N = 22 LoCalMed). Samples were prepared with Quant-IT PicoGreen dsDNA Assay kit(Invitrogen).

Statistics: Genomic data was imported to One Codex and reads were analyzed against the database(K-mer based classification, and species-level abundance estimation including genome-size adjustment). Comparisons were assessed between: LoCalMed vs UC; BMI loss≥1kg/m2 (primary endpoint) vs non-BMI loss; adherence≥75% to LoCalMed vs UC or adherence<75% by Mann-Whitney U. Volcano (R, GraphPad) and abundance plots (One Codex) were made on N = 7,965 identified species.

Results

Arrival time to WTC, age on 9/11, duration at WTC, race, smoking history, and baseline pulmonary function (FEV1, FVC, and FEV1/FVC) between LoCalMed and UC were not significantly different.

BMI loss ≥1kg/m2 significantly increased FEV1%pred(p = 0.030), and FVC%pred(p = 0.005) compared to their baseline. In addition, there was an increased abundance(red) of Dorea formicigenerans(p = 0.006), Lachnospira eligens(p = 0.017), Eubacterium sp.CAG:38(p = 0.021), Ruthenibacterium lactatiformans(p = 0.027), Amedibacterium Intestinale(p = 0.031), Bacteroides fragilis(p = 0.036), Fig-1A. In contrast, Parabacteroides distasonis(p = 0.008), Alistipes Shahii(p = 0.009), and Paraprevotella clara(p = 0.013), decreased (blue) compared to non-BMI loss subjects. Abundances of the most prominent species based on BMI loss≥1kg/m2 are shown, Fig-1B. In BMI loss≥1kg/m2, both Shannon Index(α-diversity;p=0.023), Fig-1C, and Bray-Curtis dissimilarity(β-diversity;p=0.042) significantly increased, Fig-1D.

Adherent individuals displayed higher abundance of Clostridiaceae bacterium AM27-36B(p = 0.002), Firmicutes bacterium CAG:56(p = 0.007), Eubacterium sp. CAG:38(p = 0.007), Eubacterium sp.CAG:202(0.012), Mediterraneibacter massiliensis(p = 0.023), Lachnospiraceae bacterium AM10-38(p = 0.031), and Bifidobacterium bifidum(0.041), Fig-1E. Adherent individuals exhibited an increased α-diversity(Simpson’s index;p=0.017), Fig-1F.

Conclusion

In a subset of the FIREHOUSE RCT, participants demonstrated an increased α and β diversity, consistent with the literature that a more diverse gut microbiome is associated with beneficial health outcomes. BMI loss and adherence to LoCalMed increased L. eligens and B. bifidum respectively, which have been shown to protect the integrity of the microbiome, whereas B. fragilis provides essential nutrients to maintain gut microbiome. D. formicigenerans represses colorectal tumor growth. Eubacterium sp.CAG 38 has been associated with decreased inflammation in ulcerative colitis.

This abstract is funded by: U01OH011300