Untargeted Metabolomics Reveals Intestinal Pathogenesis and Self-Repair in Rabbits Fed an Antibiotic-Free Diet

Abstract

The prohibition of the use of growth-promoting drug additives in feeds was implemented in China in 2020. However, rabbits can experience symptoms of intestinal disease, such as diarrhea and flatulence, when switching from standard normal diets with antibiotics to antibiotic-free diets. The molecular mechanisms related to the occurrence of these diseases as well as associated physiological and metabolic changes in the intestine are unclear. Thus, the objectives of this study were to study the pathogenesis of intestinal inflammation using untargeted metabolomics. This was done to identify differential metabolites between a group of antibiotic-free feed Hyplus rabbits (Dia) whose diet was abruptly changed from a standard normal diet with antibiotics to an antibiotic-free diet, and an antibiotic diet group Hyplus rabbits (Con) that was fed a standard normal diet with antibiotics. Morphological damage to the three intestinal tissues was determined through visual microscopic examination of intestinal Dia and Con tissue samples stained with hematoxylin and eosin (HE). A total of 1969 different metabolites were identified in the three intestinal tissues from Dia and Con rabbits. The level of 1280 metabolites was significantly higher and the level of 761 metabolites was significantly lower in the Dia than in the Con group. These differential metabolites were involved in five metabolic pathways associated with intestinal inflammation (tryptophan metabolism, pyrimidine metabolism, phenylalanine, tyrosine and tryptophan biosynthesis, lysine degradation, and bile secretion). Rabbits in the Dia group developed metabolic disorders that affected the intestinal microbiota and changed the permeability of the intestinal tract, thereby triggering intestinal inflammation, affecting feed utilization, reducing production performance, and activating the intestinal tract self-repair mechanism. Thus, the abrupt transition from a diet with antibiotics to an antibiotic-free diet affected the structure and metabolism of the intestinal tract in Hyplus rabbits. Consequently, to avoid these problems, the antibiotic content in a rabbit diet should be changed gradually or alternative antibiotics should be found.

Isosteviol Sodium Ameliorates Dextran Sodium Sulfate-Induced Chronic Colitis through the Regulation of Metabolic Profiling, Macrophage Polarization, and NF-κB Pathway

“…In addition, the phenylalanine, tyrosine, and tryptophan biosynthetic pathways are necessary for the production of aromatic amino acids, including tryptophan and phenylalanine. Inactivity in this pathway disturbs intestinal metabolism and promotes intestinal inflammation [ 46 ].…”

Heat Stress Affects Faecal Microbial and Metabolic Alterations of Rabbits

“…In short, the harm caused by HS to the human body is a dynamic process that can fluctuate with time and intensity; the outcomes may change depending on the research settings. Furthermore, HS may operate as the initial messenger to regulate inositol molecule, insulin signal, amino acid metabolism, and glucose metabolism network and respond to and heal body damage ( Tang et al, 2021 ; Wen et al, 2021 ).…”

“…Metabonomics is a technique for identifying and quantifying all metabolites present in biological samples. At present, Tang et al (2021) used non-targeted metabonomics to reveal the intestinal pathogenesis and self-healing of rabbits without antibiotic diet, He et al (2019a) used fecal metabonomics technology to explore the metabolic changes of heat stress in late pregnancy of primiparous sows, and Wen et al (2021) used metabonomics technology to explore the metabolic changes of heat stress on cecal contents of mice. However, the research on the relationship between heat stress and rabbit intestinal microbial ecosystem and its metabolites is still limited.…”

Microbiomics Revealed the Disturbance of Intestinal Balance in Rabbits with Diarrhea Caused by Stopping the Use of an Antibiotic Diet

“…At the end of the experiment, 6 rabbits from the normal condition were selected as the control group (Con, n = 6) and 6 rabbits from the disease condition (diarrhea) were selected as the experiment (diarrhea) group (Dia, n = 6) according to their weight, physiological condition and health status [ 26 ]. Each rabbit was fed 150–200 g diet per day and lived separately in a clean cage (600 × 600 × 500 mm, 21–23 °C, 60–75 % humidity, 14 h light (60 lx)) [ 20 ]. These animals had free access to fresh water.…”

“…Previous studies in mice have shown that gut microbes do not immediately return to normal when antibiotics are stopped, and were limited to the large intestine or small intestine [ 19 ]. The content of amino acids (Anthranilic acid, L-Tryptophan, and L-Phenylalanine) in a diarrhea group of rabbits fed without antibiotics was higher than that in a normal group [ 20 ]. Previous studies have shown that the use of antibiotics changes the link between intestinal microbes and amino acid metabolism [ 21 ].…”