(P20-045-23) Effect of Antibiotics and Fecal Microbiota Transplantation on Diet-Modulated Microbiota

Objectives: Antibiotics (ABXs), commonly prescribed to treat infections, can directly alter gut microbiota. Recovery and repopulation of the gut microbiota post-antibiotic are primarily through diet, while alternatives such as probiotics or fecal microbiota transplantations are also being explored. The objective of this analysis was to determine the efficacy of Mediterranean diet (MeDi) or Western diet (WD) FMTs to mitigate the impact of ABX on diet-modulated gut microbiota.

Methods: Male Fischer-344 rats (4 months) were randomly assigned to 1 of 5 groups: MeDi, WD, WD-MeDi FMT, MeDi-WD FMT, or MeDi-MeDi FMT (n=9/ group). After 3 months, groups received ABXs (ertapenem sodium (1 g/L) + neomycin sulfate (1 g/L) + vancomycin hydrochloride (1 g/L)) in drinking water for 3-days prior to beginning once-weekly FMTs or PBS for 2 months. Fresh fecal samples were provided by donor animals (n= 9-18/ diet). Fecal samples were collected before ABXs and 2 months post-ABXs for 16s rRNA sequencing. Microbiota was assessed using α-diversity including Shannon and Simpson indices and β-diversity including weighted UniFrac (relative abundance) and unweighted UniFrac (presence/ absence).

Results: We found that α-diversity indices did not differ by group before (Shannon, p=0.95; Simpson, p=0.62) or after ABXs (p=0.70; Simpson, p=0.87). Prior to ABXs, β-diversity was significantly different between groups with different diets (p < 0.001). After ABXs and FMTs, weighted UniFrac was different between diet control groups (p=0.02) and compared to FMT groups (p=0.002 to 0.01), but FMT groups did not differ by FMT type. For unweighted UniFrac, all groups differed (p= 0.001 to 0.04) except MeDi-MeDi FMT and MeDi-WD FMT (p=0.22). When comparing groups before and after ABXs, α-diversity (Shannon, p=0.48; Simpson, p=0.87) did not differ, however, β-diversity remained significantly different before and after ABXs for the MeDi (p≤0.001) and WD (p≤0.001) but FMT groups  were not different (p=0.14 to 0.46).

Conclusions: WD and MeDi microbiota remain distinct following ABXs indicating a diet-dependent response. Repopulation of the gut microbiota by diet-modulated FMT better restores the gut microbiota to pre-antibiotic composition while the microbiota of diet-alone groups remains distinct from pre-ABXs composition.

Funding Sources: Pennington/Louisiana Nutrition Obesity Research Center