Antibiotics administration altered microbiota composition after knockdown, donor transplant and chow diet in Lean Zucker Diabetic Fatty (LZDF) rats
Authors: Page Ryan , Guice Justin , Carvajal‐Aldaz Diana , Raggio Anne , Welsh David , Taylor Chris , Luo Meng , Blanchard Eugene , Husseneder Claudia , Tuuri Georgianna , Marx Brian , Stout Rhett , Martin Roy , Bruce‐Keller Annadora , Coulon Diana , Keenan Michael 
Published: November 2023

The composition and characteristics of various bacterial communities inhabiting the gut have been associated with regulating energy balance, immune response, and neurological functions. It is hypothesized that many of these health benefits can be attributed to the byproducts of bacteria that feed on fermentable fibers. Previous research has shown that an obese or lean host microbiota can transfer their phenotype to germ‐free recipients without an alteration in the diet. However, this transfer can be attenuated by established microbial communities in conventionally‐raised rodents or other species. In this case, a knockdown of these communities is required before a transplant to allow the microbiota of a donor to populate the gut of a recipient. The aim of this study was to examine whether obese Zucker Diabetic Fatty (ZDF) rats fed either a high fat (HF) (40% Fat, energy) or a low fat resistant starch (LFRS) (RS, 25.4% wt. diet) (Fat 11%) diet could transfer their microbiota and phenotypic properties to LZDF recipients after a knockdown of host microbiota with antibiotics (AB, vancomycin and merepenem, 50mg/kg for bw/day in drinking water). Obese ZDF donor groups (n=3) fed either a HF or a LFRS diet were euthanized after six weeks. Cecal contents collected were transplanted into two (n=6) groups of LZDF rats from either the LFRS fed obese ZDF group or the HF fed group subsequent to a microbiota knockdown using AB. Both LZDF groups were fed a chow diet and were euthanized after eight weeks. Emboweled weight (no gut contents), cecum weight, cecal pH and short‐chain fatty acids were analyzed. Statistical analyses showed no significant phenotypic differences between the LZDF recipient groups. Homeostatic model of assessment ‐ insulin resistance (HOMA‐IR) measured insulin sensitivity. LZDF RS recipients had numerically higher insulin sensitivity (p=.12). Sequencing and bioinformatics were used to determine bacterial composition. Bacterial analysis was exploratory with no a priori plan and examined each taxonomic level (Phylum, Class, Order, Family, Genus and Species) based on their relative abundance. Differences were considered significant at (p<0.05). Bacteroidetes decreased and Firmicutes increased significantly at the phylum level after AB. AB also significantly increased Clostridiales (family) and decreased Lactobacillus (genus), and Blautia (genus). LZDF HF recipients had significantly higher Actinobacteria (phylum) and Clostridiales and lower Bacteroides (genus) and Prevotella (genus) after AB, transplant and chow diet. Both LZDF groups continued to show the effect of AB on bacteria to study end. AB may not be appropriate for knockdown of microbiota. Protection methods, such as encapsulation may be required for the cecal transplant to survive gastric and bile acids.

Support or Funding Information

LSU AgCenter and Ingredion Incorporated.