Project description:This study was designed to investigate stressful social experience (SSE) in early life by examining how it can induce alterations in the microbiota-gut-brain axis. To test this, different experimental groups of pups experienced the presence of either a stranger (S) with mother (M+P+S) or without their mother (MS+S-M). Animals were assessed for anxiety-like behavior and high-throughput bacterial 16s rRNA sequencing was performed to analyze the structure of the gut microbiota. Our analysis revealed that early life SSE induced anxiety-like behavior and reduced the diversity and richness of gut microbiota. In the second experiment, all groups were supplemented with <i>Lactobacillus paracasei HT6</i>. The findings indicated that <i>Lactobacillus</i> supplementation had a significant beneficial effect on anxiety-like behavior in stressed rats (MS, M+P+S, and MS + S-M) accompanied by normalized levels of adrenocorticotropic hormone (ACTH), corticosterone (CORT), glucocorticoid receptor (GR), serotonin (5-HT), dopamine (DA), and noradrenaline (NA). Concomitantly, the expression of microRNA (miR)-124a was down-regulated and miR-132, caspase-3, glutamate receptors (GluR1, GluR 2; NR2A, and NR2B) were up-regulated in stressed groups but remained unchanged by <i>Lactobacillus</i> supplementation in stressed individuals. This indicates that stress-associated GluR1-GR altered interactions can be significantly prevented by <i>Lactobacillus</i> supplementation. Analysis of the fecal metabolite profile was undertaken to analyze the effect of <i>Lactobacillus</i>, revealing that five predicted neuroactive microbial metabolites were reduced by early life SSE. Our results showed a potential link between Lactobacillus supplementation and beneficial effects on anxiety-like behavior, the mechanism of which could be potentially mediated through stress hormones, neurotransmitters, and expression of miRNAs, glutamate receptors, and the microbiota-gut-brain axis.
Project description:Development of obesity-associated comorbidities is related to chronic inflammation, which has been linked to gut microbiota dysbiosis. Thus, modulating gut microbiota composition could have positive effects for metabolic disorders, supporting the use of probiotics as potential therapeutics in vivo, which may be enhanced by a microencapsulation technique. Here we investigated the effects of non-encapsulated or pectin-encapsulated probiotic supplementation (Lactobacillus paracasei subsp. paracasei L. casei W8®; L. casei W8) on gut microbiota composition and metabolic profile in high-fat (HF) diet-fed rats. Four male Wistar rat groups (n = 8/group) were fed 10% low-fat, 45% HF, or HF with non-encapsulated or encapsulated L. casei W8 (4 × 107 CFU/g diet) diet for seven weeks. Microbiota composition, intestinal integrity, inflammatory profiles, and glucose tolerance were assessed. Non-encapsulated and pectin-encapsulated probiotic supplementation positively modulated gut microbiota composition in HF-fed male rats. These changes were associated with improvements in gut barrier functions and local and systemic inflammation by non-encapsulated probiotics and improvement in glucose tolerance by encapsulated probiotic treatment. Thus, these findings suggest the potential of using oral non-encapsulated or encapsulated probiotic supplementation to ameliorate obesity-associated metabolic abnormalities.
Project description:OBJECTIVE:To evaluate the effectiveness and tolerability of omega-3 polyunsaturated fatty acid (PUFA) supplementation for treatment of trait anxiety among adolescent females with restrictive anorexia nervosa (AN). METHOD:A pilot double-blind, placebo-controlled randomized trial of adolescent females with AN (N?=?24) entering Partial Hospitalization Program (PHP) from January 2015 to February 2016. Participants were randomized to four daily PUFA (2,120?mg eicosapentaenoic acid/600?mg docosohexaenoic acid) or placebo capsules for 12?weeks. A 9-item questionnaire of side effect frequency assessed medication tolerability. The Beck Anxiety Inventory-Trait measured anxiety at baseline, 6, and 12?weeks. Linear mixed models evaluated associations between randomization group and study outcomes. Twenty-two and 18 participants completed 6 and 12?weeks of data collection, respectively. RESULTS:Medication side effect scores were low and were not significantly different between randomization groups at Week 6 (p?=?.20) or 12 (p?=?.41). Mean trait anxiety score significantly (p?<?.01) decreased from baseline to 12?weeks in both groups, and the rate of change over the course of time did not differ between omega-3 PUFA and placebo groups (p?=?.55). CONCLUSION:Omega-3 PUFA supplementation was well tolerated in adolescent females with AN. Although power to detect differences was limited, we found no evidence that omega-3 PUFA benefited anxiety beyond nutritional restoration.
Project description:There is increasing concern about potential long-term effects of antibiotics on children's health. Epidemiological studies have revealed that early-life antibiotic exposure can increase the risk of developing immune and metabolic diseases, and rodent studies have shown that administration of high doses of antibiotics has long-term effects on brain neurochemistry and behaviour. Here we investigate whether low-dose penicillin in late pregnancy and early postnatal life induces long-term effects in the offspring of mice. We find that penicillin has lasting effects in both sexes on gut microbiota, increases cytokine expression in frontal cortex, modifies blood-brain barrier integrity and alters behaviour. The antibiotic-treated mice exhibit impaired anxiety-like and social behaviours, and display aggression. Concurrent supplementation with Lactobacillus rhamnosus JB-1 prevents some of these alterations. These results warrant further studies on the potential role of early-life antibiotic use in the development of neuropsychiatric disorders, and the possible attenuation of these by beneficial bacteria.
Project description:BACKGROUND:Recently factors in the relationship between gut microbiota, obesity, diabetes and the metabolic syndrome have been suggested in the development and progression of nonalcoholic steatohepatitis (NASH). In this sense, this work aims to evaluate the effects of probiotic supplementation on intestinal microbiota modulation, degree of hepatic steatosis and fibrosis, inflammation, gut permeability, and body composition. METHODS:This double-blind, randomized clinical trial will include adult outpatients with a diagnosis of NASH confirmed by biopsy with or without transient elastography. All patients will undergo a complete anamnesis to investigate their alcohol consumption, previous history, medications, nutritional assessment (dietary intake and body composition), sarcopenia, physical activity level and physical and functional capacity, cardiovascular risk, biochemical parameters for assessment of inflammatory status, lipid profile, hepatic function, gut permeability, and assessment of microbiota. These procedures will be performed at baseline and repeated after 24?weeks (at the end of the study). Through the process of randomization, patients will be allocated to receive treatment A or treatment B. Both patients and researchers involved will be blinded (double-blind study). The intervention consists of treatment with a probiotic mix (Lactobacillus acidophillus?+?Bifidobacterium lactis?+?Lactobacillus rhamnosus?+?Lactobacillus paracasei, 1 x 109 CFU for each) and the placebo which is identical in all its characteristics and packaging. Patients will be instructed to consume two sachets/day during 24?weeks and to report any symptoms or side effects related to the use of the sachets. Adherence control will be carried out through the patient's notes on a form provided, and also by checking the number of sachets used. DISCUSSION:The final results of study will be analyzed and disseminated in 2020. TRIAL REGISTRATION:ClinicalTrials.gov, ID: NCT03467282 . Registered on 15 March 2018.
Project description:It has been shown that gut dysbiosis can be associated with the development of type 2 diabetes mellitus (T2DM). Consequently, intervention with probiotics may be a useful approach to improve metabolic variables in diabetes. The present study aimed to evaluate the efficacy of <i>L. paracasei</i> HII01 on glycemia in T2DM patients. In a randomized, double-blind, placebo-controlled study, 50 participants were allocated to receive <i>L. paracasei</i> HII01 (50 × 10<sup>9</sup> CFU/day) or a placebo (corn starch 10 mg/day). Blood and fecal samples were assessed at baseline and at the end of the trial. After 12 weeks of intervention, fasting blood glucose level had significantly decreased in the probiotic group compared with the placebo group. Importantly, probiotic supplementation significantly decreased the plasma levels of LPS, TNF-α, IL-6 and hsCRP compared the placebo group. Additionally, an increase in beneficial bacteria and a decrease in pathogenic bacteria, which related to the improvement of SCFAs, was found following <i>L. paracasei</i> HII01 supplementation. These findings demonstrated that <i>L. paracasei</i> HII01 improved hyperglycemia and inflammatory markers by favorably modifying gut microbiota and subsequently ameliorating the leaky gut and endotoxemia, thereby suggesting a potential role as an adjuvant treatment in type 2 diabetes.
Project description:Adolescents frequently engage in risky behaviours such as binge drinking. Binge drinking, in turn, perturbs neurodevelopment reinforcing reward seeking behaviour in adulthood. Current animal models are limited in their portrayal of this behaviour and the assessment of neuroimmune involvement (specifically the role of Toll-like receptor 4 (TLR4)). Therefore, the aims of this project were to develop a more relevant animal model of adolescent alcohol exposure and to characterise its effects on TLR4 signalling and alcohol-related behaviours later life. Balb/c mice received a short (P22-P25), low dose alcohol binge during in early adolescence, and underwent tests to investigate anxiety (elevated plus maze), alcohol seeking (conditioned place preference) and binge drinking behaviour (drinking in the dark) in adulthood. Four doses of alcohol during adolescence increased alcohol-induced conditioned place preference and alcohol intake in adulthood. However, this model did not affect basal elevated plus maze performance. Subsequent analysis of nucleus accumbal mRNA, revealed increased expression of TLR4-related mRNAs in mice who received alcohol during adolescence. To further elucidate the role of TLR4, (+)-Naltrexone, a biased TLR4 antagonist was administered 30 min before or after the adolescent binge paradigm. When tested in adulthood, (+)-Naltrexone treated mice exhibited reduced alcohol intake however, alcohol seeking and anxiety behaviour was unaltered. This study highlights that even a small amount of alcohol, when given during a critical neurodevelopmental period, can potentiate alcohol-related behaviours and TLR4 activation later in life. Interestingly, attenuation of TLR4 before or after adolescent alcohol exposure reduced only binge alcohol intake in adulthood.
Project description:The human gut microbiota is an important environmental factor for human health with evolutionarily conserved roles in immunity, metabolism, development, and behavior of the host. Probiotic organisms are claimed to offer several functional properties including stimulation of immune system. The purpose of this study is to investigate the effects of a probiotic supplementation on adult volunteers who have contracted the common cold four or more times in the past year. This study is a single center, double-blind, randomized, controlled, prospective trial. Subjects received a probiotic drink containing Lactobacillus paracasei (at least 3?×?107 colony forming units (CFU) ml-1), Lactobacillus casei 431® (at least 3?×?107?CFU?ml-1) and Lactobacillus fermentium PCC® (at least 3?×?106?CFU?ml-1) or an identical placebo without probiotics for a 12-week study period. The consumption of probiotics significantly reduced the incidence of upper respiratory infection (p?<?0.023) and flu-like symptoms with an oral temperature higher than 38?°C (p?<?0.034) as compared to the placebo group. Subjects that consumed probiotics demonstrated a significantly higher level of IFN-? in the serum (p?<?0.001) and sIgA in the gut (p?<?0.010) as compared to the placebo group and a significant higher level of serum IFN-? (p?<?0.001) and gut sIgA (p?<?0.001) as compared to their baseline test results. In contrast, there were no significant differences in the serum IL-4, IL-10, IgA, IgG or IgM between the probiotics and the placebo groups. Results of this study demonstrated that probiotics were safe and effective for fighting the common cold and influenza-like respiratory infections by boosting the immune system.
Project description:INTRODUCTION:The gut microbiota is involved in the regulation of cognition, mood, anxiety, and pain, and can impact cognitive functions by producing neuroactive substances or releasing bacterial by-products and metabolites. No information is available on the effects of a probiotic supplementation on brain function of HIV+ subjects. In light of the above considerations, we performed a pilot study in cART-treated HIV-1-positive patients with long-term virologic suppression. The aims were to analyze the effect of high-concentration multistrain probiotic supplementation (Vivomixx®; Visbiome®) on several neurocognitive abilities and to evaluate the safety of this supplementation. METHODS:To address those issues, neurocognitive performances were explored by administering neuropsychological tests; moreover, miRNA-29a-c levels were measured in cerebrospinal fluid (CSF) to confirm the persistent undetectable levels of HIV-RNA in the central nervous system after probiotic supplementation. RESULTS:Our results show that the Rey auditory verbal learning test (RAVLT) (immediate and delayed recall), Rey-Osterrieth complex figure test (ROCF) (copy immediate and delayed recall), phonological verbal fluency (PVF) test, Toronto alexithymia scale-20 (Tas-20), State-trait anxiety inventory Y-2 (STAY Y-2), and time and weight estimation test (STEP) scores improved significantly during the study. Moreover, we found unchanged levels, associated to high degree of individual variability, in miRNA-29 levels in CSF collected before and after probiotic supplementation. CONCLUSIONS:In conclusion, we observed that HIV patients treated with 6 months of this probiotic supplementation appear to have an improvement in some neurocognitive functions; moreover, this approach is safe and did not modify significantly the levels of miRNA in CSF. Further studies are needed to better understand the contribution of the probiotics in modulating gut-brain-axis in HIV patients.
Project description:Probiotics are well known for their beneficial effects for animals, including humans and livestock. Here, we tested the probiotic activity of Lactobacillus paracasei expressing 3D8 scFv, a nucleic acid-hydrolyzing mini-antibody, in mice intestine. A total of 18 fecal samples derived from three different conditions at two different time points were subjected to high-throughput 16S ribosomal RNA (rRNA) metagenomic analyses. Bioinformatic analyses identified an average of 290 operational taxonomic units. After administration of L. paracasei, populations of the probiotics L. paracasei, Lactobacillus reuteri, and Pediococcus acidilactici increased, whereas the population of harmful bacteria such as Helicobacter species decreased. Furthermore, continuous administration of L. paracasei resulted in L. paracasei emerging as the dominant probiotic after competition with other existing probiotics. Expression of 3D8 scFv protein specifically increased the population of P. acidilactici, which is another probiotic. In summary, our results showed that L. paracasei expressing 3D8 scFv protein enhanced probiotic activity in mice intestine with no observable side effects. Thus, the system developed in this study may be a good tool for the expression of recombinant protein using probiotics.