Colonic lesions, cytokine profiles, and gut microbiota in plasminogen-deficient mice

Plasminogen-deficient (FVB/NPan-plg(tm1Jld), plg(tm1Jld)) mice, which are widely used as a wound-healing model, are prone to spontaneous rectal prolapses. The aims of this study were 1) to evaluate the fecal microbiome of plg(tm1Jld) mice for features that might contribute to the development of rectal prolapses and colonic inflammation and 2) to assess the relevance of the inflammatory phenotype to the variability in wound healing in this model. The plg(tm1Jld) mice exhibited delayed wound healing, and they could be divided into 3 distinct groups that differed according to the time until wound closure. Colonic lesions in plg(tm1Jld) mice, which were characterized by necrotizing ulcerations and cystically dilated glands, were restricted to the intermediate and distal parts of the colon. The cytokine profile was indicative of chronic tissue damage, but the genetic modification did not change the composition of the gut microbiota, and none of the clinical or biochemical parameters correlated with the gut microbiota composition

A Possible Link between Food and Mood: Dietary Impact on Gut Microbiota and Behavior in BALB/c Mice

<div><p>Major depressive disorder is a debilitating disease in the Western World. A western diet high in saturated fat and refined sugar seems to play an important part in disease development. Therefore, this study is aimed at investigating whether saturated fat or sucrose predisposes mice to develop behavioral symptoms which can be interpreted as depression-like, and the possible influence of the gut microbiota (GM) in this. Fourty-two mice were randomly assigned to one of three experimental diets, a high-fat, a high-sucrose or a control diet for thirteen weeks. Mice on high-fat diet gained more weight (p = 0.00009), displayed significantly less burrowing behavior than the control mice (p = 0.034), and showed decreased memory in the Morris water maze test compared to mice on high-sucrose diet (p = 0.031). Mice on high-sucrose diet burrowed less goal-oriented, showed greater latency to first bout of immobility in the forced swim test when compared to control mice (p = 0.039) and high-fat fed mice (p = 0.013), and displayed less anxiety than mice on high-fat diet in the triple test (p = 0.009). Behavioral changes were accompanied by a significant change in GM composition of mice fed a high-fat diet, while no difference between diet groups was observed for sucrose preferences, LPS, cholesterol, HbA1c, BDNF and the cytokines IL-1α, IL-1β, IL-6, IL-10, IL-12(p70), IL-17 and TNF-α. A series of correlations was found between GM, behavior, BDNF and inflammatory mediators. In conclusion, the study shows that dietary fat and sucrose affect behavior, sometimes in opposite directions, and suggests a possible association between GM and behavior.</p></div

Dietary-induced differences in cecal microbial composition.

<p>The table shows bacterial OTU's which differs with a significant <i>p</i>-value between diet groups. A high-fat diet impacts the GM composition, significantly increasing the abundance of Firmicutes, primarily within the family Ruminococcaceae, and reducing the abundance of the family S24-7 within the Bacteoidetes phylum. <i>P</i>-values and the FDR-corrected <i>p</i>-values are listed.</p

The Burrowing test.

<p>Mice on HF diet removed significantly less bedding material from the tube than mice on C diet (p = 0.035). A tendency of reduced burrow-digging is seen for mice on HS diet (p = 0.064). However, although not quantified, this diet group burrowed less goal-oriented, as observations showed excessive digging in the whole cage. Median with ranges.</p

Multiple linear regression analysis between GM and behavior, cytokines, and BDNF.

<p>Several significant associations are seen between GM and both behavior and systemically circulating inflammatory mediators, indicating a possible influence from the gut on the immune system and the brain. Furthermore a certain GM composition seems to be associated with both improved memory and increased levels of BDNF in mice not subjected to any of the experimental diets. The PCoA analysis denotes whether data was weighted (W) or not (UW) by bacterial abundance and the principal component (PC) listed denotes the significant factor(s) in the multiple linear regression models. Not shown and non-significant are: Risk assessment on OA, Time spent in OF center and PFC BDNF. GM was not correlated to IL-1β, IL-10 and TNF-α, as all samples were at basal concentrations regarding these cytokines. <i>Italic: negative correlation</i>. <b>Bold: Positive correlation</b>.</p