Prevention of gut leakiness by a probiotic treatment leads to attenuated HPA response to an acute psychological stress in rats.

BACKGROUND AND AIMS: Intestinal barrier impairment is incriminated in the pathophysiology of intestinal gut disorders associated with psychiatric comorbidity. Increased intestinal permeability associated with upload of lipopolysaccharides (LPS) translocation induces depressive symptoms. Gut microbiota and probiotics alter behavior and brain neurochemistry. Since Lactobacillus farciminis suppresses stress-induced hyperpermeability, we examined whether (i) L. farciminis affects the HPA axis stress response, (ii) stress induces changes in LPS translocation and central cytokine expression which may be reversed by L. farciminis, (iii) the prevention of "leaky" gut and LPS upload are involved in these effects. METHODS: At the end of the following treatments female rats were submitted to a partial restraint stress (PRS) or sham-PRS: (i) oral administration of L. farciminis during 2 weeks, (ii) intraperitoneal administration of ML-7 (a specific myosin light chain kinase inhibitor), (iii) antibiotic administration in drinking water during 12 days. After PRS or sham-PRS session, we evaluated LPS levels in portal blood, plasma corticosterone and adrenocorticotropic hormone (ACTH) levels, hypothalamic corticotropin releasing factor (CRF) and pro-inflammatory cytokine mRNA expression, and colonic paracellular permeability (CPP). RESULTS: PRS increased plasma ACTH and corticosterone; hypothalamic CRF and pro-inflammatory cytokine expression; CPP and portal blood concentration of LPS. L. farciminis and ML-7 suppressed stress-induced hyperpermeability, endotoxemia and prevented HPA axis stress response and neuroinflammation. Antibiotic reduction of luminal LPS concentration prevented HPA axis stress response and increased hypothalamic expression of pro-inflammatory cytokines. CONCLUSION: The attenuation of the HPA axis response to stress by L. farciminis depends upon the prevention of intestinal barrier impairment and decrease of circulating LPS levels.

In vitro screening of probiotics and synbiotics according to anti-inflammatory and anti-proliferative effects.

There is emerging evidence of the efficiency of probiotic, prebiotic and synbiotic treatments in inflammatory bowel diseases (IBDs) and one of their long-term complications, colorectal cancer (CRC). In this study, various strains of probiotic lactic acid bacteria, prebiotic glucooligosaccharides (GOS) or a synbiotic combination of the two were screened for anti-inflammatory and anti-proliferative effects in different in vitro models in the context of such diseases. To mimic IBD response to Gram negative bacteria, HT-29 cells were sensitised to inflammatory response to lipopolysaccharide (LPS) by IFNγ which increased expression of TLR4, the LPS biosensor, and were then treated by probiotics, prebiotics and synbiotics. Secreted IL-8 and activated NF-κB were monitored as inflammation biomarkers. A selection of active strains were then subjected to a second inflammatory cell culture model consisting of inflammatory activated transgenic Caco-2 cells transfected by a reporter gene under the control of NF-κB inducible promoter. Quantification of reporter gene expression allowed us to demonstrate some probiotic inhibitory properties or to confirm such characteristics in two different models. Proliferation of cancerous HT-29 cells was monitored by XTT assay. Only three probiotic strains induced a proliferation decrease, but with a lack of reproducibility. Binary or ternary probiotic associations, complemented or not by prebiotic GOS, significantly decreased proliferation, especially with a synbiotic association of Bifidobacterium breve, Lactococcus lactis and oligoalternan, a GOS. This combination was selected for the following experiments. We showed the involvement of both bacterial and carbohydrate compounds of this synbiotic in the observed effect by dose range tests. We demonstrated that this decrease in proliferation may be due to an induction of a differentiated phenotype, as shown by the up-regulation of intestinal alkaline phosphatase, a biomarker of differentiation, monitored by real-time RT-PCR in HT-29 cells treated by the selected synbiotics. Thus, this study demonstrates the ability of probiotics to exert anti-inflammatory effects and shows some anti-proliferative characteristics for a specific synbiotics. These products should be further evaluated in animal models to confirm the in vitro results.

Efficacy of a synbiotic supplementation in the prevention of common winter diseases in children: a randomized, double-blind, placebo-controlled pilot study.

BACKGROUND AND AIMS: The purpose of this study was to investigate the efficacy of a synbiotic supplementation in reducing common winter diseases in children. METHODS: A randomized, double-blind, placebo-controlled, multicentre study was conducted in young school-age children (3-7 years old) during a winter period. Participants were otherwise healthy children who suffered from at least three episodes of ear, nose and throat (ENT), respiratory tract or gastrointestinal illness during the previous winter. They were supplemented daily with either a synbiotic preparation (Lactobacillus helveticus R0052, Bifidobacterium infantis R0033, Bifidobacterium bifidum R0071, and fructooligosaccharide) or a matched placebo for 3 months. Over this period, all emergent health episodes of any type were recorded by parents in a diary. They were checked by investigators at regular monthly visits. The main study outcome was the percentage of children free of any episode during the study course. RESULTS: We randomized 135 children (mean age: 4.1±1.0 years) to the synbiotic group (n = 62) or placebo (n = 73) group. At least one illness episode was reported in 32 children in the synbiotic group and 50 in the placebo group (51.6% versus 68.5%). This corresponded to a significant 25% relative risk reduction (95% CI 0.6-44.3%; p = 0.045). This difference was due to a decrease in the number of children who suffered from at least one ENT, respiratory tract or gastrointestinal disorder (50.0% with synbiotic versus 67.1% with placebo; p = 0.044). At least one sickness school day loss was noted in 25.8% of children with the synbiotic as compared with 42.5% with placebo (p = 0.043). No treatment related side effects were detected in either group. CONCLUSIONS: This study suggests that a 3-month supplementation with this synbiotic preparation can decrease the risk of occurrence of common infectious diseases in children and limits the risk of school day loss.

In vitro screening of probiotic lactic acid bacteria and prebiotic glucooligosaccharides to select effective synbiotics.

Probiotics and prebiotics have been demonstrated to positively modulate the intestinal microflora and could promote host health. Although some studies have been performed on combinations of probiotics and prebiotics, constituting synbiotics, results on the synergistic effects tend to be discordant in the published works. The first aim of our study was to screen some lactic acid bacteria on the basis of probiotic characteristics (resistance to intestinal conditions, inhibition of pathogenic strains). Bifidobacterium was the most resistant genus whereas Lactobacillus farciminis was strongly inhibited. The inhibitory effect on pathogen growth was strain dependent but lactobacilli were the most effective, especially L. farciminis. The second aim of the work was to select glucooligosaccharides for their ability to support the growth of the probiotics tested. We demonstrated the selective fermentability of oligodextran and oligoalternan by probiotic bacteria, especially the bifidobacteria, for shorter degrees of polymerisation and absence of metabolism by pathogenic bacteria. Thus, the observed characteristics confer potential prebiotic properties on these glucooligosaccharides, to be further confirmed in vivo, and suggest some possible applications in synbiotic combinations with the selected probiotics. Furthermore, the distinctive patterns of the different genera suggest a combination of lactobacilli and bifidobacteria with complementary probiotic effects in addition to the prebiotic ones. These associations should be further evaluated for their synbiotic effects through in vitro and in vivo models.

Probiotic food supplement reduces stress-induced gastrointestinal symptoms in volunteers: a double-blind, placebo-controlled, randomized trial.

Stress plays an important role in the development of symptoms contributing to disease. Stress induces various disorders with gastrointestinal, physical, and psychological symptoms. Probiotics can help regulate or modulate gastrointestinal functions. The aim of the present study was to investigate the effects of a probiotic preparation (Probio-Stick) on stress-induced symptoms in volunteers. A double-blind, placebo-controlled, randomized study was conducted on volunteers with symptoms of stress. Subjects received a probiotic (Probio-Stick; Lallemand SAS, Saint-Simon, France) containing Lactobacillus acidophilus Rosell-52 and Bifidobacterium longum Rosell-175 (3 x 10(9) colony-forming units per sachet stick) or a sensorially identical placebo without probiotics during a 3-week period. The consumption of probiotics significantly reduced 2 stress-induced gastrointestinal symptoms (abdominal pain and nausea/vomiting) for intention-to-treat or per-protocol populations. In contrast, the probiotics did not significantly modify the other physical and psychological symptoms and sleep problems induced by stressful life events for intention-to-treat or per-protocol populations. The results indicate that Probio-Stick can provide a beneficial effect on the gastrointestinal symptoms experienced by individuals affected by chronic stress.