Immunological effects of reduced mucosal integrity in the early life of BALB/c mice

Abstract

Certain stimuli at the gut barrier may be necessary in early life to establish a proper balance of immune tolerance. We evaluated a compromised barrier in juvenile mice in relation to microbiota and local and systemic immunity. BALB/c mice were treated with a low dose of dextran sulfate sodium (DSS) with or without ampicillin and lipopolysaccharide (LPS) to clarify the importance of microbial antigens and interaction between microbial-associated patterns and toll-like receptors. The barrier breach resulted in increased plasma LPS, which was highest in mice treated simultaneously with ampicillin. Adding LPS in the food reduced its levels in plasma. Regulatory T cells were acutely increased in mesenteric lymph nodes (MLN) and spleen during DSS treatment regardless of simultaneous ampicillin treatment. In contrast, NK T and NK cells decreased in MLN and in spleen. This acute DSS effect was reflected in fold changes of haptoglobin and Il1a in colon, and this was also more pronounced in mice simultaneously treated with ampicillin. On day 1 post-treatment, major upregulations of Ifng, Foxp3, Il1b, Il2, and Il6 genes in colon were only observed in the mice simultaneously treated with ampicillin. A two-fold upregulation of colonic Foxp3 and Il1a was evident 25 days post-treatment. DSS skewed the microbiota in favor of Gram negative phyla. Therefore, increased permeability induced tolerogenic immunity independent of microbiota, and this was enhanced by LPS stimulation.

Faecal virome transplantation decreases symptoms of type 2 diabetes and obesity in a murine model

“…For the liver, genes involved in metabolic pathways (triglyceride, carbohydrate, bile and cholesterol metabolism) and inflammation were selected. For the ileum, genes involved in inflammation, GM signalling and gut barrier function were selected 30 31. Primer sequences are listed in online supplementary tables S2 and S3.…”

Reduced early life mucosal integrity decreases thymic cell counts and increases local, but not thymic regulatory, T cell recruitment: Gut mucosal integrity breach and thymic T cells

“…In each experiment, animals were randomized into three treatment groups. Based on earlier treatment protocols 23,25,26,39,40,46 at 5 weeks of age, control group mice received regular tap water ad libitum throughout the experiment period, the low-dose group received 1.5% DSS (molecular weight of Effects of low-and high-dose dextran sulfate sodium (DSS) on gut permeability and cytokine expression in BALB/c mice (control, low dose (1.5%), and high dose (4%)). (a) Study timeline for Experiments 1 and 2.…”

“…15 The mucin-feeding bacterium Akkermansia muciniphila with an abundance of up to 3% of the gut bacteria 17 is protective against, for example, type 1 diabetes (T1D), 18,19 inflammatory bowel disease (IBD), 20 autism, 21 and diet-induced obesity. 22 Previously, we developed a mouse model, in which a low dose of drinking water dextran sulfate sodium (DSS) is used as an artificial mucin degrader, 23 which increased the abundance of A. muciniphila and decreased the abundance of segmented filamentous bacteria (SFBs). 23 We also observed increased Tregs in the mesenteric lymph nodes (MLNs) and the spleen, and decreased natural killer (NK) and NKT cells, while colonic expression of Foxp3 and Il1a was twofold upregulated 25 days after treatment.…”

“…22 Previously, we developed a mouse model, in which a low dose of drinking water dextran sulfate sodium (DSS) is used as an artificial mucin degrader, 23 which increased the abundance of A. muciniphila and decreased the abundance of segmented filamentous bacteria (SFBs). 23 We also observed increased Tregs in the mesenteric lymph nodes (MLNs) and the spleen, and decreased natural killer (NK) and NKT cells, while colonic expression of Foxp3 and Il1a was twofold upregulated 25 days after treatment. 23 Vancomycin lowers the incidence of T1D in newborn T1D-prone non-obese diabetic (NOD) mice, and it propagates both A. muciniphila and proteobacteria-carrying lipopolysaccharide (LPS), which is a microbial-associated molecular pattern (MAMP).…”

“….000-50.000; MP Biomedicals, Santa Ana, CA, USA), while the high-dose group received 4% DSS in regular tap water ad libitum for 7 days (Experiment 1: n = 6-8/group per time point; Experiment 2: n = 7-8/group or n = 5-6/group on day 3 of treatment and day 2 after treatment, respectively, based on power calculation on previous data 23,25,26 ). Body weight (BW), food, and water intake were registered weekly.…”