Alterations to the microbiota–colon–brain axis in high-fat-diet-induced obese mice compared to diet-resistant mice

Abstract

Obesity is underpinned by both genetic and environmental factors, including a high-saturated-fat diet. Some mice develop diet-induced obesity (DIO), but others remain diet resistant (DR) despite intake of the same high-saturated-fat diet, a phenomenon that mimics characteristics of the human obese phenotype. Microbiota-colon-brain axis regulation is important for energy metabolism and cognition. Using DIO and DR mouse models, this study aimed to examine gut microbiota, colonic inflammation and cognitive function to elucidate the role of microbiota-gut-brain regulation in DIO. C57Bl6/J mice fed a chronic saturated-palmitic-acid diet for 22 weeks showed significant body weight gain differences, with the top one third gaining 48% heavier body weight than the lower one third. There was significant reduction in gut microbiota richness and diversity in DIO mice but not in DR mice. At the phylum level, DIO mice had increased abundance of Firmicutes and Antinobacteria, and decreased abundance of Bacterioides and Proteobacteria in gut microbiota. DIO mice exhibited reduced tight junction proteins, increased plasma endotoxin lipopolysaccharide (LPS) and increased inflammation in the colon and liver. Recognition memory and spatial memory were impaired in DIO mice, associated with decreased Bacteroidetes. Further examination showed that hippocampal brain-derived neurotrophic factor was significantly decreased in DIO mice (vs. DR). Conversely, DR mice showed no changes in the above parameters measured. Therefore, gut microbiota, colon inflammation and circulating LPS may play a major role in the development of the obese phenotype and cognitive decline associated with a chronic high-saturatedpalmitic-acid diet.

Supplement of microbiota-accessible carbohydrates prevents neuroinflammation and cognitive decline by improving the gut microbiota-brain axis in diet-induced obese mice

“…Microbial DNA extraction, PCR amplification, and Miseq sequencing in cecal contents Genomic DNA amplification and sequencing were conducted as our previous study [5]. Briefly, microbial DNA was extracted from the cecal contents of mice using the E.Z.N.A.…”

“…There is increasing evidence that diet can influence the gut microbiome, consequently modulating brain functions and subsequent behavior, through the gut-brain axis. For example, high-fat dietinduced gut microbiota alterations can induce cognitive impairment in mice [5]. In addition, obese-type microbiota transplantation has shown to disrupt the intestinal barrier and induce cognition decline in mice [6].…”

“…Previous studies demonstrate Ruminococcus of Firmicutes phylum degrades mucus [10], while Bacteroides fragilis of Bacteriodetes phylum increases tight junction expression and attenuates intestinal permeability [11]. Increased intestinal permeability allows translocation of bacterial lipopolysaccharide (LPS, endotoxin) into the blood circulation (endotoxemia) [5], which can trigger a neuroinflammatory response [12,13]. In line with this, systemic LPS administration has shown to activate microglia and astrocytes (principal immune cells in the central nervous system) and increase pro-inflammatory cytokine expression in the hippocampus of mice [14].…”

β-glucan from Lentinula Edodes Prevents Cognitive Impairments in High-Fat Diet-Induced Obese Mice: Involvement of Colon-Brain Xxis

“…The temporal order memory test was performed based on methods previously described [16]. Brie y, the experiment comprised two sample trials and one test trial with an inter-trial interval of 60 min between each trial.…”

“…Moreover, evidence from germ-free, antibiotic-treated and pathogen-free rodents has revealed gut microbiota dysbiosis negatively affect hippocampal neurogenesis and brain development via microglia activation [11,12], suggesting a vital role of gut microbiota in cognitive function. Therefore, the gut-brain axis is considered as the potential therapeutic target for HF induced neuroin ammation and cognitive decline [13][14][15][16].…”