Hypothesis: We previously presented highly significant differences in the bacterial community structures of human renal allograft recipients over time. Likewise, murine normal, colitic, and pregnant fecal samples influenced cardiac allograft survival and were markedly distinct in bacterial community structure, notably, in abundance of Bifidobacterium. We hypothesized that these differences persist after fecal microbiota transplant (FMT) into mice with cardiac allografts and correlate with allograft outcome.

Methods: Mice were fed antibiotics (kanamycin, gentamicin, colistin, metronidazole, vancomycin) ad libitum in drinking water on days -6 to -1 before transplant. On d0 C57BL/6 mice received BALB/c hearts. Fecal samples from healthy C57BL/6, female mice on d11 of pregnancy, colitic T cell receptor transgenic mice that spontaneously develop colitis, or cultured Bifidobacterium pseudolongum (ATCC25526) were transferred on d0 by gavage. Mice received daily immunosuppression tacrolimus (2 mg/kg/d sc d0-40 or 3 mg/kg/d sc d0-60) starting on day 0. Fecal pellets and intestinal tissue were collected from transplanted mice, and analyzed via 16S rRNA gene sequencing and RNA-Seq. Cardiac allografts were assessed for survival, harvested at d40, 60, or rejection, and stained with H&E and Masson's Trichrome.

Results: 16S rRNA gene analysis of transplant recipient samples revealed highly significant differences in the bacterial community structures of recipients of normal, colitic, and pregnant FMT, and cultured B. pseudolongum, as determined by bacterial composition and relative abundance, principle component analysis and hierarchical clustering. Bacteria from the genus Bifidobacterium were absent in colitic, yet present in normal and pregnant source samples and remained fairly abundant in pregnant transplanted samples for at least 40 days. In general the microbiota of recipients of normal, colitic, and pregnant fecal samples converged over time, but remained distinct for at least 40 days. Mice receiving pregnant FMT or B. pseudolongum had the highest graft survival rates, indicating a possible anti-inflammatory effect of Bifidobacterium bacteria.

Conclusion: FMT of pro- and anti-inflammatory fecal microbiota and specific components of the microbiota results in durable changes to host microbiota. These changes correlate with alterations in systemic immunity with consequences for graft survival, rejection, and inflammation.

CITATION INFORMATION: Brinkman C, Hittle L, Fricke W, Mongodin E, Bromberg J. Fecal Microbiota Transplant Results in Durable Changes to Host Microbiota That Correlate with Allograft Outcome. Am J Transplant. 2016;16 (suppl 3).

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