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ARS Home » Southeast Area » Little Rock, Arkansas » Microbiome and Metabolism Research Unit » Research » Publications at this Location » Publication #342072
Title: Associations among the cecal microbiome and bacterially-derived cecal xeno-metabolites during diabetes progression in the UC Davis-Type 2 diabetes rat model

Author
item PICCOLO, BRIAN - Arkansas Children'S Nutrition Research Center (ACNC)
item GRAHAM, JAMES - University Of California
item WANKHADE, UMESH - Arkansas Children'S Nutrition Research Center (ACNC)
item NOOKAEW, INTAWAT - University Of Arkansas
item MERCER, KELLY - Arkansas Children'S Nutrition Research Center (ACNC)
item SHANKAR, KARTIK - Arkansas Children'S Nutrition Research Center (ACNC)
item HAVEL, PETER - University Of California
item Ferruzzi, Mario

Submitted to: American Diabetes Association Meeting
Publication Type: Abstract Only
Publication Acceptance Date: 2/27/2017
Publication Date: N/A
Citation: N/A

Interpretive Summary:

Technical Abstract: The gut microbiome is altered in obesity and diabetes, but the molecular signals linking gut microbes and host metabolic regulation have not been established. Our aim was to identify gut microbe-derived xeno-metabolites that associate with alterations in the microbiome during the progression of a type 2 diabetes-like phenotype. Cecal contents were collected from chow-fed and age-matched male UC Davis Type-2-Diabetes Rats before the onset of diabetes (PD, n = 15), 2 wk recently-diabetic (RD, n = 10), 3 mos (D3M n = 11) and 6 mos (D6M n = 7) post-onset of diabetes. Microbial profiles were assessed using amplicon sequencing of 16S rRNA, and xeno-metabolites were assessed by LC-MS. Only p-cresol sulfate, serotonin, adenine, and inosine were significantly altered by diabetes stage (P < 0.05; ANOVA). Actinobacteria abundance decreased from early to late stages of diabetes and was positively associated with indole-3-acetic acid (in PD rats) and hydroxy-hydrocinnamic acid (in D6M rats). Bacteroidetes, Tenericutes, and Cyanobacteria were positively associated with cecal 3-hydroxybenzoic acid and suberic acid in PD rats; however, negative associations were found among Tenericutes and suberic acid following diabetes onset. Bacterial diversity was positively associated with 3-hydroxybenzoic acid, p-cresol sulfate, isobutyric acid, glycylvaline, TMAO, and 2-methylbutyric acid in PD rats, but negatively associated with 3-hydroxybenzoic acid and glycylvaline in D3M and D6M rats. These associations provide evidence that microbial metabolism is altered during host diabetes progression, even when controlling for diet, sex, strain and housing factors known to confound microbiome interpretations in rodent and human obesity and type 2 diabetes studies. The specific signals from the host that regulate xenometabolism and microbe populations remain to be elucidated.