title: The Colonic Microbiome and Epithelial Transcriptome Are Altered in Rats Fed a High-Protein Diet Compared with a Normal-Protein Diet.
abstract: BACKGROUND
  A high-protein diet (HPD) can produce hazardous compounds and reduce butyrate-producing bacteria in feces, which may be detrimental to gut health. However, information on whether HPD affects intestinal function is limited.
  
  
  OBJECTIVE
  The aim of this study was to determine the impact of an HPD on the microbiota, microbial metabolites, and epithelial transcriptome in the colons of rats.
  
  
  METHODS
  Adult male Wistar rats were fed either a normal-protein diet (20% protein, 56% carbohydrate) or an HPD (45% protein, 30% carbohydrate) for 6 wk (n = 10 rats per group, individually fed). After 6 wk, the colonic microbiome, microbial metabolites, and epithelial transcriptome were determined.
  
  
  RESULTS
  Compared with the normal-protein diet, the HPD adversely altered the colonic microbiota by increasing (P < 0.05) Escherichia/Shigella, Enterococcus, Streptococcus, and sulfate-reducing bacteria by 54.9-fold, 31.3-fold, 5.36-fold, and 2.59-fold, respectively. However, the HPD reduced Ruminococcus (8.04-fold), Akkermansia (not detected in HPD group), and Faecalibacterium prausnitzii (3.5-fold) (P < 0.05), which are generally regarded as beneficial bacteria in the colon. Concomitant increases in cadaverine (4.88-fold), spermine (31.2-fold), and sulfide (4.8-fold) (P < 0.05) and a decrease in butyrate (2.16-fold) (P < 0.05) in the HPD rats indicated an evident shift toward the production of unhealthy microbial metabolites. In the colon epithelium of the HPD rats, transcriptome analysis identified an upregulation of genes (P < 0.05) involved in disease pathogenesis; these genes are involved in chemotaxis, the tumor necrosis factor signal process, and apoptosis. The HPD was also associated with a downregulation of many genes (P < 0.05) involved in immunoprotection, such as genes involved in innate immunity, O-linked glycosylation of mucin, and oxidative phosphorylation, suggesting there may be an increased disease risk in these rats. The abundance of Escherichia/Shigella, Enterococcus, and Streptococcus was positively correlated (Spearman's ρ > 0.7, P < 0.05) with genes and metabolites generally regarded as being involved in disease pathogenesis, suggesting these bacteria may mediate the detrimental effects of HPDs on colonic health.
  
  
  CONCLUSIONS
  Our findings suggest that the HPD altered the colonic microbial community, shifted the metabolic profile, and affected the host response in the colons of rats toward an increased risk of colonic disease.
authors: Jiangsu Key Laboratory of Gastrointestinal Nutrition and Animal Health, Laboratory of Gastrointestinal Microbiology, College of Animal Science and Technology, Nanjing Agricultural University, Nanjing, China; and.
authors: Chunlong
authors: C
authors: Mu
authors: Jiangsu Key Laboratory of Gastrointestinal Nutrition and Animal Health, Laboratory of Gastrointestinal Microbiology, College of Animal Science and Technology, Nanjing Agricultural University, Nanjing, China; and.
authors: Yuxiang
authors: Y
authors: Yang
authors: Jiangsu Key Laboratory of Gastrointestinal Nutrition and Animal Health, Laboratory of Gastrointestinal Microbiology, College of Animal Science and Technology, Nanjing Agricultural University, Nanjing, China; and.
authors: Zhen
authors: Z
authors: Luo
authors: Department of Agricultural, Food and Nutritional Science, University of Alberta, Edmonton, Alberta, Canada.
authors: Leluo
authors: L
authors: Guan
authors: Jiangsu Key Laboratory of Gastrointestinal Nutrition and Animal Health, Laboratory of Gastrointestinal Microbiology, College of Animal Science and Technology, Nanjing Agricultural University, Nanjing, China; and zhuweiyun@njau.edu.cn.
authors: Weiyun
authors: W
authors: Zhu
mesh_terms: D000818:Animals; D004269:DNA, Bacterial / Q000302:isolation & purification; D004032:Diet; D004044:Dietary Proteins / Q000008:administration & dosage*; D015536:Down-Regulation; D016983:Enterococcus / Q000302:isolation & purification; D004925:Escherichia / Q000302:isolation & purification; D005243:Feces / Q000382:microbiology; D000069196:Gastrointestinal Microbiome; D020869:Gene Expression Profiling; D008297:Male; D009077:Mucins / Q000378:metabolism; D012336:RNA, Ribosomal, 16S / Q000302:isolation & purification; D051381:Rats; D017208:Rats, Wistar; D045857:Ruminococcus / Q000302:isolation & purification; D012760:Shigella / Q000302:isolation & purification; D013291:Streptococcus / Q000302:isolation & purification; D059467:Transcriptome
chemical_list: D004269:DNA, Bacterial; D004044:Dietary Proteins; D009077:Mucins; D012336:RNA, Ribosomal, 16S
keywords: bacterial metabolites; colonic disease risk; colonic microbiome; epithelial response; epithelial transcriptome; high-protein diet; microbial community