David Philippe

Selection of Bifidobacteria Based on Adhesion and Anti-Inflammatory Capacity In Vitro for Amelioration of Murine Colitis

ABSTRACT Adhesion and anti-inflammatory properties of eight strains of bifidobacteria were tested using the intestinal epithelial cell lines Caco-2, T84, and HT29. Two strains were selected for further assessment of their anti-inflammatory capacity in two murine models of colitis. In vivo results confirmed the high anti-inflammatory capacity of a Bifidobacterium bifidum strain.

Treatment with Bifidobacterium bifidum 17 partially protects mice from Th1-driven inflammation in a chemically induced model of colitis

Probiotics have been suggested as an alternative therapeutical approach in the intervention of inflammatory disorders of the gastrointestinal tract (GIT). Application of single strains or probiotic mixtures has shown promising results in animal models and patients of inflammatory bowel disease (IBD). We recently demonstrated potent inhibitory capacity of a Bifidobacterium bifidum S17 on LPS-induced inflammatory events in cell culture models using intestinal epithelial cells and verified these anti-inflammatory effects in two mouse models of colitis. In the present study we analyze the anti-inflammatory effect of this potential probiotic strain in a chemically-induced model of colitis in C57BL/6 mice. This model is characterized by a strong type 1T helper (Th1) response resembling Crohns disease, one of the two most prevalent forms of IBD. We performed macroscopic analysis and determined the effect of B. bifidum S17 on the cytokine balance in biopsies of the colonic mucosa. While treatment with B. bifidum S17 only had a marginal effect on weight loss, no difference was observed in the macroscopic parameters. However, a significant reduction in histology scores and the levels of pro-inflammatory cytokines interleukin 1β (IL-1β), interleukin 6 (IL-6), keratinocyte-derived chemokine (KC) and the inflammatory markers cyclooxigenase 2 (Cox-2) and myeloperoxidase (MPO) was observed. These results indicate that treatment with B. bifidum S17 is able to partially inhibit the strong Th1-driven intestinal inflammation induced in our model of colitis.

Bifidobacterium lactis attenuates onset of inflammation in a murine model of colitis

AIM To assess the anti-inflammatory effect of the probiotic Bifidobacterium lactis (B. lactis) in an adoptive transfer model of colitis. METHODS Donor and recipient mice received either B. lactis or bacterial culture medium as control (deMan Rogosa Sharpe) in drinking water for one week prior to transfer of a mix of naive and regulatory T cells until sacrifice. RESULTS All recipient mice developed signs of colonic inflammation, but a significant reduction of weight loss was observed in B. lactis-fed recipient mice compared to control mice. Moreover, a trend toward a diminution of mucosal thickness and attenuated epithelial damage was revealed. Colonic expression of pro-inflammatory and T cell markers was significantly reduced in B. lactis-fed recipient mice compared to controls. Concomitantly, forkhead box protein 3, a marker of regulatory T cells, was significantly up-regulated by B. lactis. CONCLUSION Daily oral administration of B. lactis was able to reduce inflammatory and T cells mediators and to promote regulatory T cells specific markers in a mouse model of colitis.

Interleukin-18 protein level is upregulated in adipose tissue of obese mice.

In this study, we investigated the regulation of Interleukin‐18 (IL‐18) and caspase‐1 mRNA and protein levels in adipose and liver tissue of obese (ob/ob) mice compared with ob/+ mice. In ob/ob mice, which have a twofold higher IL‐18 plasma level as compared with lean mice, IL‐18 mRNA expression was significantly reduced by 1.6‐fold in adipose tissue, whereas protein level was enhanced fourfold as compared with ob/+ mice. However, caspase‐1 mRNA expression and activity were significantly enhanced in adipose tissue of ob/ob mice. Conversely, both IL‐18 mRNA and protein levels were slightly enhanced, but caspase‐1 activity was reduced in liver of ob/ob mice as compared with lean mice. In conclusion, we show that adipose and hepatic IL‐18 protein expressions are increased in obese mice. However, in contrast to liver, the adipose IL‐18 protein level appears to be upregulated through a post‐transcriptional mechanism probably involving caspase‐1.

Randomised double-blind placebo-controlled study of the effect of Lactobacillus paracasei NCC 2461 on skin reactivity

In recent decades, the prevalence of subjects with reactive skin has considerably increased in industrialised countries. 50% of women and 30% of men report cutaneous discomfort classified under reactive/sensitive skin. Several topical approaches have been proposed, in particular through improvement of galenic forms or protection of epidermal surface. We propose to act differently, deeply from inside the body via an innovative nutritional approach. To this purpose, Lactobacillus paracasei NCC 2461 (ST11) was selected because of its specific beneficial skin properties discovered in in vitro studies, i.e. diminution of neurogenic inflammation and promotion of the recovery of skin barrier function. We designed a randomised double-blind placebo-controlled clinical study with a two-month supplementation in two female treatment groups (n=32 per group). A capsaicin test was performed to monitor the time course of skin sensitivity. Moreover, transepidermal water loss was assessed to analyse the rate of skin barrier function recovery; dryness of the leg and roughness of the cheeks was investigated by a dermatologist as well as by self-assessment. The results of the present clinical trial show that oral supplementation with the probiotic decreases skin sensitivity and increases the rate of barrier function recovery. Thus, the data provide evidence that daily intake of ST11 could improve reactive skin condition.

Immune modulation property of Lactobacillus paracasei NCC2461 (ST11) strain and impact on skin defences.

The gut intestinal tract harbours a complex microbiota. Disturbances in the microbiota composition have been associated with several immune dysfunctions such as inflammatory diseases. Specific strains of probiotics have shown to beneficially influence the composition and/or metabolic activity of the endogenous microbiota. Taking advantage of the plasticity of the immune system, the probiotic strain NCC2461 (i.e. ST11 or CNCM I-2116) supports and/or restores homeostasis in reaction to different physiopathological conditions. The potential of NCC2461 to modulate both mucosal and systemic immune functions led us to test its impact on skin physiology. Even though clear mechanisms explaining gut-skin interaction are still lacking, a set of experimental and clinical data reviewed herein have shown that NCC2461 exerts its effects beyond the gut and confers benefits at the skin level. It contributes to the reinforcement of skin barrier function, decreases skin sensitivity and modulates the skin immune system leading to the preservation of skin homeostasis.

Oral Lactobacillus paracasei improves skin barrier function recovery and reduces local skin inflammation.

ejd.2010.1242 Auteur(s) : David PHILIPPE david.philippe@rdls.nestle.com, Stephanie BLUM, Jalil BENYACOUB Nestle Research Center, Lausanne, Vers chez les blanc, P.O. Box 44, CH-1000, Switzerland Recently, the incidence of subjects presenting dry skin and eczema has considerably increased in industrialized countries [1]. Dry skin is characterized by marked sensitivity of skin to physical (heat, cold…) or chemical (topical product application) stimuli and is often associated with an impairment of [...]

Anti-inflammatory effects of Lacto-Wolfberry in a mouse model of experimental colitis

AIM To investigate the anti-inflammatory properties of Lacto-Wolfberry (LWB), both in vitro and using a mouse model of experimental colitis. METHODS The effects of LWB on lipopolysaccharide (LPS)-induced reactive oxygen species (ROS) and interleukin (IL)-6 secretion were assessed in a murine macrophage cell line. in vitro assessment also included characterizing the effects of LWB on the activation of NF-E2 related 2 pathway and inhibition of tumor necrosis factor-α (TNF-α)-induced nuclear factor-κB (NF-κB) activation, utilizing reporter cell lines. Following the in vitro assessment, the anti-inflammatory efficacy of an oral intervention with LWB was tested in vivo using a preclinical model of intestinal inflammation. Multiple outcomes including body weight, intestinal histology, colonic cytokine levels and anti-oxidative measures were investigated. RESULTS LWB reduced the LPS-mediated induction of ROS production [+LPS vs 1% LWB + LPS, 1590 ± 188.5 relative luminescence units (RLU) vs 389 ± 5.9 RLU, P < 0.001]. LWB was more effective than wolfberry alone in reducing LPS-induced IL-6 secretion in vitro (wolfberry vs 0.5% LWB, 15% ± 7.8% vs 64% ± 5%, P < 0.001). In addition, LWB increased reporter gene expression via the anti-oxidant response element activation (wolfberry vs LWB, 73% ± 6.9% vs 148% ± 28.3%, P < 0.001) and inhibited the TNF-α-induced activation of the NF-κB pathway (milk vs LWB, 10% ± 6.7% vs 35% ± 3.3%, P < 0.05). Furthermore, oral supplementation with LWB resulted in a reduction of macroscopic (-LWB vs +LWB, 5.39 ± 0.61 vs 3.66 ± 0.59, P = 0.0445) and histological scores (-LWB vs +LWB, 5.44 ± 0.32 vs 3.66 ± 0.59, P = 0.0087) in colitic mice. These effects were associated with a significant decrease in levels of inflammatory cytokines such as IL-1β (-LWB vs +LWB, 570 ± 245 μg/L vs 89 ± 38 μg/L, P = 0.0106), keratinocyte-derived chemokine/growth regulated protein-α (-LWB vs +LWB, 184 ± 49 μg/L vs 75 ± 20 μg/L, P = 0.0244), IL-6 (-LWB vs +LWB, 318 ± 99 μg/L vs 117 ± 18 μg/L, P = 0.0315) and other pro-inflammatory proteins such as cyclooxygenase-2 (-LWB vs +LWB, 0.95 ± 0.12 AU vs 0.36 ± 0.11 AU, P = 0.0036) and phosphorylated signal transducer and activator of transcription-3 (-LWB vs +LWB, 0.51 ± 0.15 AU vs 0.1 ± 0.04 AU, P = 0.057). Moreover, antioxidant biomarkers, including expression of gene encoding for the glutathione peroxidase, in the colon and the plasma anti-oxidant capacity were significantly increased by supplementation with LWB (-LWB vs +LWB, 1.2 ± 0.21 mmol/L vs 2.1 ± 0.19 mmol/L, P = 0.0095). CONCLUSION These results demonstrate the anti-inflammatory properties of LWB and suggest that the underlying mechanism is at least in part due to NF-κB inhibition and improved anti-oxidative capacity.