High Fat Diet Alters Gut Microbiota and the Expression of Paneth Cell-Antimicrobial Peptides Preceding Changes of Circulating Inflammatory Cytokines

Abstract

Obesity is an established risk factor for many diseases including intestinal cancer. One of the responsible mechanisms is the chronic inflammation driven by obesity. However, it remains to be defined whether diet-induced obesity exacerbates the intestinal inflammatory status by cytokines produced in adipose tissue or the high fat diet first alters the gut microbiota and then drives intestinal inflammation. To address this question, we fed C57BL/6 mice with a high fat diet (HF, 60%) and sacrificed them sequentially after 8, 12, and 16 weeks, and then compositions of gut microbiota and expressions of antimicrobial peptides were determined. The compositions of gut microbiota were altered at 8 wk HF feeding, followed with reduced Paneth antimicrobial peptides lysozyme and Reg IIIγ after 12 and 16 wk HF feeding (p < 0.05), whereas elevations of circulating inflammatory cytokines IFNγ and TNF-α were observed until feeding a HF diet for 16 weeks (p < 0.05). These results indicated that high fat diet may stimulate intestinal inflammation via altering gut microbiota, and it occurs prior to the potential influence by circulating inflammatory cytokines. These findings emphasized the importance of microbiota, in addition to adipose tissue per se, in driving intestinal inflammation, which may thereafter promote intestinal tumorigenesis.

Impact of maternal malnutrition on gut barrier defence: implications for pregnancy health and fetal development.

“…Additionally, fetuses from HF mothers showed an increase in gut mRNA expression levels of AMP genes Lyz1 (but not Lyz2), Defa1, and Reg3g. This is in contrast to studies in adult mice (35,40,60,70) that have demonstrated that HF diets decrease gut levels of AMPs, though one study (37) found differing results between the mRNA and protein levels. Nevertheless, our study is the first to our knowledge to uncover how maternal malnutrition alters expression levels of AMPs in near-term fetuses and is the first to assess Reg3g mRNA expression in fetal tissues.…”

“…Extensive research has demonstrated that high-fat diets markedly alter the diversity and composition of gut microbes (40,(60)(61)(62)(63)(64), resulting in long-term aberrations in gut barrier integrity (40,(60)(61)(62)65) and function (40,60,66) and chronic inflammation (40,61,62). As a result, we hypothesised that mothers fed a HF diet would show pronounced changes in gut function.…”

“…In response to both over- (35) and undernutrition (36), collectively known as malnutrition, gut barrier function and integrity can become dysregulated, leading to gut microbial dysbiosis, altered gut function, and a leaky gut barrier. Yet, few studies have elucidated the effects of malnutrition on Paneth cell (37)(38)(39)(40)(41) and EGC (42,43) development and function (indeed, none have examined EGCs during undernutrition to our knowledge), or how either of these cells are affected by and/or perpetuate gut dysfunction. Since the rates of both undernutrition and underweight (44), as well as over-nutrition and obesity (44), are increasing worldwide, and a compromised gut barrier is both caused by, and leads to, a variety of immune-related, and chronic diseases, the effects of malnutrition on the gut-host relationship are important to understand.…”

Exercise improves high fat diet-impaired vascular function

“…As anticipated, HFD increased the level of aortic ROS, serum leptin and resistin, which further prompted aortic tissue maladaptive immune response and release of proinflammatory cytokines, including MCP1, IL6 and IL8. It has been demonstrated that HFD and high-fructose beverages increased body weight, leptin, inflammation and insulin resistance that are associated with steatosis, and oxidative stress in plasma and tissues, indicating that oxidative stress and inflammation are important contributors to the pathogenesis of CVD (20,21).…”

Relationship Between Oligosaccharides and Glycoconjugates Content in Human Milk and the Development of the Gut Barrier

“…This is known as the entero-mammary pathway. At least 200 bacterial species have been isolated from human milk but the great diversity is linked to the variations in the culture methods or geographical differences (Li et al, 2017). Bacteria from the phylum Proteobacteria, Firmicutes (Pannaraj et al, 2017), and Bifidobacteria have been found in human milk (Cabrera-Rubio, Mira-Pascual, Mira, & Collado, 2016).…”