Lactobacillus Helveticus R0052 Research Articles

Probiotics Alter the Microbial and Behavioral Consequences of Methamphetamine Exposure in a Sex-Selective Manner

Methamphetamine use disorder (MuD) is a global health problem, with no FDA-approved medications. Our prior work demonstrated that repeated methamphetamine exposure alters the gut microbiota in male rats and results in depressive-like behaviors. In this study, we extend our findings to females and determine whether probiotics block these effects. Male and female rats were administered methamphetamine (2 mg/kg; SC) or saline twice daily with either a combination of two probiotics (Lactobacillus helveticus R0052 and Bifidobacterium longum R0175) or placebo solution for 14 days. Fecal samples were collected at baseline and other days after treatment cessation. Tests of anxiety- and depressive-like behaviors were conducted using open-field and forced-swim assays. Methamphetamine induced anxiety-like behavior in females and anxiety-like and depressive-like behaviors in males. Probiotics blocked the depressive-like effect in males but did not alter anxiety-like effects in either sex. Methamphetamine exposure decreased levels of alpha diversity in both sexes, but sex differences were seen in the ability of probiotics or methamphetamine to alter levels of various bacteria. These findings support the role of the gut–brain microbiome in the depressive effects of repeated methamphetamine exposure in males, suggesting that probiotics may be a viable treatment option for MuD.

A39 DEVELOPMENTALLY REGULATED CECAL CONTENT MICRO-RNAS CORRELATE WITH MATURING MICROBIOTA GENES AND FUNCTIONS IN JUVENILE MICE

Abstract Background The gut microbiome establishment in early life is critical to life-long health and influenced by the maternal gut ecosystem. MicroRNAs (miRNAs) have emerged as a new player in host-microbiota interaction due to their regulatory effect on bacterial genes. We previously found that maternal supplementation with a probiotic mix of Lacticaseibacillus rhamnosus R0011 and Lactobacillus helveticus R0052 supported the maturation of microbial metabolic activity and altered the cecal content miRNA profile in juvenile mice. Aims To investigate the relationship between cecal content miRNAs and inferred microbiota genes and functions in early life and identify potential miRNA-bacterial gene targets. Methods We generated 16S rRNA gene sequencing and NanoString nCounter® data from the cecal content of 14, 21, and 36-days-old C57BL/6 mice born to dams receiving or not probiotic-supplemented water since preconception. Taxa contributions to bacterial enzyme-encoding genes and pathways were inferred with PICRUSt2. Time or group-altered genes, pathways, and miRNAs were identified with DESeq2. Spearman correlations were performed between miRNAs and bacterial genes or pathways (n= 3-5 male offspring/PND/group) and significant correlations (q ampersand:003C 0.05) were visualized with NAViGaTOR. Potential miRNA binding sites on bacterial genes were investigated using the ViennaRNA Package. Results Time-associated miR-433 positively correlated with two time-altered genes involved in the TCA and glyoxylate cycles. Group-associated miR-691 was positively correlated with genes related to tRNA charging pathway, pyruvate fermentation to acetate and lactate, and amino acids biosynthesis. Additionally, miR-691 was negatively correlated with six group-altered genes involved in myo-inositol degradation. We identified potential miRNA binding sites (total free energy of binding ampersand:003C -10 kcal/mol) for miR-691 with genes involved in pyruvate fermentation, lysine biosynthesis, and myo-inositol degradation, and for miR-433 with genes annotated to the TCA and glyoxylate cycles. Conclusions Host miRNAs correlate with bacterial pathways and genes maturing during the weaning transition, highlighting their potential to regulate microbial metabolic activity. Maternal probiotics supplementation may accelerate the development of microbial metabolic pathways through epigenetic mechanisms, independently of weaning dietary shift. Correlations identified include energy production pathways and may become clinical targets in infants with delayed maturation of the intestinal ecosystem. Funding Agencies NSERC

Efficacy and safety of Lacticaseibacillus rhamnosus R0011 and Lactobacillus helveticus R0052 as an adjuvant for Helicobacter pylori eradication: a double-blind, randomized, placebo-controlled study

BackgroundHelicobacter pylori eradication is recommended as a way of providing symptomatic relief for dyspepsia. The limited efficacy of triple therapy is a major problem in many countries, including Thailand. Some probiotics have been shown to improve the H. pylori eradication rate and reduce side effects. This study aimed at evaluating the efficacy of probiotic (Lacidofil® STRONG) as adjuvant to standard triple therapy.MethodsThis randomized, double-blind, placebo-controlled study was conducted between July 2020 and June 2022. Eligible patients with H. pylori gastritis (i.e., n=90 out of the 160 patients screened) were randomized to receive 14-day standard triple therapy either with probiotics or with a placebo (N=45/group). The treatment regimen entailed 30 mg lansoprazole administered twice daily, 1,000 mg amoxicillin administered twice daily, and 1 g clarithromycin modified-release formulation administered once daily. A probiotic capsule containing Lacticaseibacillus rhamnosus R0011 and Lactobacillus helveticus R0052 (Lacidofil® STRONG) or placebo were given twice daily during the eradication therapy and for an additional 4 weeks. Successful H. pylori eradication was defined as a negative 13C-urea breath test at least 4 weeks after complete eradication.ResultsAs per-protocol analysis, eradication rates after the 14-day regimen with probiotic or placebo were 90.9% and 75.0% (p=0.047), respectively. Antibiotic susceptibility testing demonstrated high clarithromycin resistance (24%). For clarithromycin-resistant strains, there was no statistical difference in eradication rates between the probiotic and placebo groups. Furthermore, probiotic supplementation significantly reduced treatment side effects, including bloating (OR 0.27 [95% CI 0.10 to 0.75], p=0.012), diarrhea (OR 0.23 [95% CI 0.28 to 0.65], p=0.006), nausea (OR 0.05 [95% CI 0.01 to 0.36], p=0.003), and bitter taste (OR 0.14 [95% CI 0.03 to 0.69], p=0.015). In addition, the probiotic group had lower gastrointestinal symptom rating scale (GSRS) scores (1.46 ± 0.36 vs. 2.65 ± 0.66, p<0.001) and higher SF-36 health-related quality-of-life scores (63.3 ± 10.2 vs. 57.3 ± 13.4, p=0.020) after treatment than the placebo group.ConclusionThe probiotic adjuvant with 14-day standard triple therapy improved the H. pylori eradication rate. Supplementation with Lacidofil® STRONG during the 2-week eradication treatment and 4-week follow-up phase can help to reduce the gastrointestinal side effects of eradication therapy and increase patients’ general health-related quality of life.

USE OF PROBIOTICS IN ALLERGIC RHINITS: A PILOT STUDY

Allergic rhinitis (AR) is a nasal inflammatory disease. It manifests itself with nasal obstruction/blockage, rhinorrhea, itching and sneezing in response to contact with allergens. Its diagnosis is clinical and confirmed with allergy tests. Its treatment may involve antihistamines, topical corticosteroids, as well as immunotherapy, which is considered the only treatment capable of altering the clinical history of the disease. To evaluate the use of probiotics to control allergic rhinitis symptoms. This is a comparative experimental pilot study in which 11 adult employees were evaluated in 4 weeks and, of these, 9 were also evaluated in 8 weeks. Everyone used 0.9% physiological solution, budesonide 200 mcg/day nasally and desloratadine, when necessary. Among the volunteers, 7 also used the combination of probiotics, Lactobacillus helveticus R0052 and Bifidobacterium longum R0175, one capsule a day. There was statistical relevance in the probiotic group for sneezing in the 4-week evaluation and for nasal obstruction in the 8-week evaluation. The results of this comparative pilot study may have been influenced by the small sample size. Even so, it was possible to find data with statistical relevance that confirmed the benefit of using probiotics, mainly to reduce sneezing and nasal obstruction. Despite being a promising form of RA treatment, more studies are needed on the use of probiotics for this purpose.

Major depression disorder - etiology and treatment

Introduction and purpose: The problem of major depression disorder (MDD) affects more and more people. In a few years, it may become the most common disease after cardiovascular diseases and cancer. MDD are manifested by a depressed mood, decreased energy, loss of interest and the ability to enjoy life, as well as a number of other additional symptoms. Untreated MDD can lead to disability. This entails not only consequences for the sick person but also increased social costs. That is why it is so important to know the causes of its formation and to look for new therapeutic methods.
 State of knowledge: The development of MDD is influenced by genetic factors, inflammatory factors and hormonal disorders, changes in the structure of the brain, disorders in neurotransmission. The microbiome-gut-brain axis affects mood regulation and neurotransmission in the brain. Bacteria such as Escherichia, Shigella, Enterococcus, Streptococccus, Alistipes, Parabacterioides, Veillonella have been identified as having a potential negative effect on the development of MDD and response to treatment. The use of probiotics containing Lactobacillus helveticus R0052, Bifidobacterium longum and Clostridium butyricum MIYAIRI 588 may help reduce the symptoms of MDD. In recent years, the US Food and Drug Administration (FDA) has approved the intranasal preparation of esketamine for the treatment of treatment-resistant depression and major depressive disorder with severe suicidal thoughts. Unlike other antidepressants, it has a quick effect on reducing symptoms.
 Summary: Due to the global problem of MDD, further research is needed to better understand the mechanisms of its formation. Particular attention should be paid to the influence of microbiota.

Total Transit Time and Probiotic Persistence in Healthy Adults: A Pilot Study

Motility, stool characteristics, and microbiota composition are expected to modulate probiotics' passage through the gut but their effects on persistence after intake cessation remain uncharacterized. This pilot, open-label study aims at characterizing probiotic fecal detection parameters (onset, persistence, and duration) and their relationship with whole gut transit time (WGTT). Correlations with fecal microbiota composition are also explored. Thirty healthy adults (30.4 ± 13.3 years) received a probiotic (30 × 109 CFU/capsule/day, 2 weeks; containing Lactobacillus helveticus R0052, Lacticaseibacillus paracasei HA-108, Bifidobacterium breve HA-129, Bifidobacterium longum R0175, and Streptococcus thermophilus HA-110). Probiotic intake was flanked by 4-week washout periods, with 18 stool collections throughout the study. WGTT was measured using 80% recovery of radio-opaque markers. Tested strains were detected in feces ~1-2 days after first intake and persistence after intake cessation was not significantly different for R0052, HA-108, and HA-129 (~3-6 days). We identified 3 WGTT subgroups within this population (named Fast, Intermediate, and Slow), which could be classified by machine learning with high accuracy based on differentially abundant taxa. On average, R0175 persisted significantly longer in the intermediate WGTT subgroup (~8.5 days), which was mainly due to 6 of the 13 Intermediate participants for whom R0175 persisted ≥ 15 days. Machine learning classified these 13 participants according to their WGTT cluster (≥ 15 days or < 5 days) with high accuracy, highlighting differentially abundant taxa potentially associated with R0175 persistence. These results support the notion that host-specific parameters such as WGTT and microbiota composition should be considered when designing studies involving probiotics, especially for the optimization of washout duration in crossover studies but also for the definition of enrollment criteria or supplementation regimen in specific populations.

Psychobiotic Effects on Anxiety Are Modulated by Lifestyle Behaviors: A Randomized Placebo-Controlled Trial on Healthy Adults.

Psychobiotics are modulators of the Microbiota-Gut-Brain Axis (MGBA) with promising benefits to mental health. Lifestyle behaviors are established modulators of both mental health and the MGBA. This randomized placebo-controlled clinical trial (NCT04823533) on healthy adults (N = 135) tested 4 weeks of probiotic supplementation (Lactobacillus helveticus R0052 and Bifidobacterium longum R0175). We assessed effects on wellbeing, quality of life, emotional regulation, anxiety, mindfulness and interoceptive awareness. We then analyzed if lifestyle behaviors modulated probiotic effectiveness. Results showed no significant effects of probiotic intake in whole sample outcomes. Correlational analyses revealed Healthy Behaviors were significantly correlated with wellbeing across scales. Moreover, the linear mixed-effects model showed that the interaction between high scores in Healthy Behaviors and probiotic intake was the single significant predictor of positive effects on anxiety, emotional regulation, and mindfulness in post-treatment outcomes. These findings highlight the relevance of controlling for lifestyle behaviors in psychobiotic and mental health research.

Comparison of changes in fermented milk quality due to differences in the proteolytic system between Lactobacillus helveticus R0052 and Lactococcus lactis subsp. lactis JCM5805

As the healthy diet concept has gained broad acceptance, more and more consumers nowadays prefer to drink fermented milk. Indeed, the quality of fermented milk is influenced by the protein hydrolysis capacity of the bacterial strains used. In this study, we conducted an in silico analysis of the composition of the proteolytic system in the genomes of Lactobacillus helveticus R0052 and Lactococcus lactis subsp. lactis JCM5805, and assessed the impact of these two strains on the quality of fermented milk from several perspectives. The results showed that L. helveticus R0052 and L. lactis JCM5805 had different cell envelope proteases, oligopeptides ABC transport system, and peptidases in their protein hydrolysis systems, which resulted in significant differences in protein hydrolysis, pH, acidity, viable bacteria count, water holding capacity and texture of the produced fermented milk. Differences in the metabolic profiles and pathways of volatile and non-volatile flavor substances between L. helveticus R0052 and L. lactis JCM5805 were identified by metabolomics. L. helveticus R0052 improves the sensory quality of fermented milk compared to L. lactis JCM5805. Our study findings provide novel insights into selecting suitable strains to produce fermented milk from a genetic and metabolic perspective.

Maternal Administration Of Probiotic Lactobacilli Since Pre-Conception Programs Offspring Gut Microbiota Functions

ObjectivesProbiotics intake may be considered beneficial by prospective and pregnant mothers but their effects on offspring development are underexplored. The maternal gut microbiota is a determinant of early offspring gut microbial colonization patterns and pre-conception may be a critical period. Our aim was to assess the programming effects of a probiotic Lacticaseibacillus rhamnosus R0011 and Lactobacillus helveticus R0052 mixture, which is known to support intestinal homeostasis in infancy, on the temporal dynamics of offspring gut microbiota functions.MethodsFemale C57BL/6 specific pathogen free mice received sterile or probiotic-supplemented water starting one week before mating and until weaning (postnatal day, PND, 21). Offspring remained on their respective mother's treatment from PND 21 to 36. Offspring cecal microbiota was profiled at PND 14, 21, and 36 by 16S rRNA (V3-V4) gene amplicon sequencing and metabolic pathways were inferred with PICRUSt2 and the MetaCyc database. Data analysis and clustering were conducted with DESeq2-Wald test and hclust in R.Results355 MetaCyc pathways were predicted and collapsed into 48 functional classes; 10 of these accounted for more than 80% of the total pathway relative abundance, including various biosynthetic as well as carbohydrate and protein degradation pathways. With time, 113 and 55 pathways were altered (q-values < 0.01) in the control and probiotic groups, respectively, but only control samples clustered by age. At PND 14 and 21,195 and 39 pathways were differentially represented in the probiotic group vs. controls, but none at PND 36. Age-dependent pathways altered by probiotic supplementation belonged to biosynthesis (Amino Acid, Nucleoside and Nucleotide, Cofactor, Electron Carrier, and Vitamin) and degradation (Carbohydrate, Nucleoside and Nucleotide, Secondary Metabolite Degradation, C1 Compound Utilization and Assimilation) functional classes.ConclusionsMaternal probiotic supplementation accelerates the establishment of gut microbiota metabolic functions necessary to process host diet as well as for the synthesis of metabolites relevant for host health in the juvenile offspring.Funding SourcesNSERC; Lallemand Health Solutions; Lawson Family Chair in Microbiome Research.

Probiotic Mixture Containing Lactobacillus helveticus, Bifidobacterium longum and Lactiplantibacillus plantarum Affects Brain Responses Toward an Emotional Task in Healthy Subjects: A Randomized Clinical Trial.

BackgroundEvidence from preclinical studies suggests that probiotics affect brain function via the microbiome-gut-brain axis, but evidence in humans remains limited.ObjectiveThe present proof-of-concept study investigated if a probiotic product containing a mixture of Bifidobacterium longum R0175, Lactobacillus helveticus R0052 and Lactiplantibacillus plantarum R1012 (in total 3 × 109 CFU/day) affected functional brain responses in healthy subjects during an emotional attention task.DesignIn this double-blinded, randomized, placebo-controlled crossover study (Clinicaltrials.gov, NCT03615651), 22 healthy subjects (24.2 ± 3.4 years, 6 males/16 females) were exposed to a probiotic intervention and a placebo for 4 weeks each, separated by a 4-week washout period. Subjects underwent functional magnetic resonance imaging while performing an emotional attention task after each intervention period. Differential brain activity and functional connectivity were assessed.ResultsAltered brain responses were observed in brain regions implicated in emotional, cognitive and face processing. Increased activation in the orbitofrontal cortex, a region that receives extensive sensory input and in turn projects to regions implicated in emotional processing, was found after probiotic intervention compared to placebo using a cluster-based analysis of functionally defined areas. Significantly reduced task-related functional connectivity was observed after the probiotic intervention compared to placebo. Fecal microbiota composition was not majorly affected by probiotic intervention.ConclusionThe probiotic intervention resulted in subtly altered brain activity and functional connectivity in healthy subjects performing an emotional task without major effects on the fecal microbiota composition. This indicates that the probiotic effects occurred via microbe-host interactions on other levels. Further analysis of signaling molecules could give possible insights into the modes of action of the probiotic intervention on the gut-brain axis in general and brain function specifically. The presented findings further support the growing consensus that probiotic supplementation influences brain function and emotional regulation, even in healthy subjects. Future studies including patients with altered emotional processing, such as anxiety or depression symptoms are of great interest.Clinical Trial Registration[http://clinicaltrials.gov/], identifier [NCT03615651].

Probiotic Mixture Containing Lactobacillus helveticus, Bifidobacterium longum and Lactiplantibacillus plantarum Affects Brain Responses to an Arithmetic Stress Task in Healthy Subjects: A Randomised Clinical Trial and Proof-of-Concept Study.

Probiotics are suggested to impact physiological and psychological stress responses by acting on the gut-brain axis. We investigated if a probiotic product containing Bifidobacterium longum R0175, Lactobacillus helveticus R0052 and Lactiplantibacillus plantarum R1012 affected stress processing in a double-blinded, randomised, placebo-controlled, crossover proof-of-concept study (NCT03615651). Twenty-two healthy subjects (24.2 ± 3.4 years, 6 men/16 women) underwent a probiotic and placebo intervention for 4 weeks each, separated by a 4-week washout period. Subjects were examined by functional magnetic resonance imaging while performing the Montreal Imaging Stress Task (MIST) as well as an autonomic nervous system function assessment during the Stroop task. Reduced activation in regions of the lateral orbital and ventral cingulate gyri was observed after probiotic intervention compared to placebo. Significantly increased functional connectivity was found between the upper limbic region and medioventral area. Interestingly, probiotic intervention seemed to predominantly affect the initial stress response. Salivary cortisol secretion during the task was not altered. Probiotic intervention did not affect cognitive performance and autonomic nervous system function during Stroop. The probiotic intervention was able to subtly alter brain activity and functional connectivity in regions known to regulate emotion and stress responses. These findings support the potential of probiotics as a non-pharmaceutical treatment modality for stress-related disorders.

Probiotics Exhibit Strain-Specific Protective Effects in T84 Cells Challenged With Clostridioides difficile-Infected Fecal Water.

Clostridioides difficile infection (CDI) is frequently associated with intestinal injury and mucosal barrier dysfunction, leading to an inflammatory response involving neutrophil localization and upregulation of pro-inflammatory cytokines. The severity of clinical manifestations is associated with the extent of the immune response, which requires mitigation for better clinical management. Probiotics could play a protective role in this disorder due to their immunomodulatory ability in gastrointestinal disorders. We assessed five single-strain and three multi-strain probiotics for their ability to modulate CDI fecal water (FW)-induced effects on T84 cells. The CDI-FW significantly (p < 0.05) decreased T84 cell viability. The CDI-FW-exposed cells also exhibited increased pro-inflammatory cytokine production as characterized by interleukin (IL)-8, C-X-C motif chemokine 5, macrophage inhibitory factor (MIF), IL-32, and tumor necrosis factor (TNF) ligand superfamily member 8. Probiotics were associated with strain-specific attenuation of the CDI-FW mediated effects, whereby Saccharomyces boulardii CNCM I-1079 and Lacticaseibacillus rhamnosus R0011 were most effective in reducing pro-inflammatory cytokine production and in increasing T84 cell viability. ProtecFlor™, Lactobacillus helveticus R0052, and Bifidobacterium longum R0175 showed moderate effectiveness, and L. rhamnosus GG R0343 along with the two other multi-strain combinations were the least effective. Overall, the findings showed that probiotic strains possess the capability to modulate the CDI-mediated inflammatory response in the gut lumen.

A randomized controlled trial to evaluate the effect of influenza vaccination and probiotic supplementation on immune response and incidence of influenza-like illness in an elderly population in Indonesia.

AimTo investigate the effect of influenza vaccination with or without probiotic supplementation on the immune response and incidence of influenza-like illness (ILI) in the elderly.MethodsA randomized double-blind, placebo-controlled trial with a modified factorial design was conducted in 554 healthy elderly subjects aged 67 ± 5.6 (ranging from 60–90) years old in the Primary Health Care Center (Puskesmas area) of the Pulo Gadung District East Jakarta. Subjects received either a trivalent influenza vaccine or placebo at the start of the study, and a probiotic supplement (Lactobacillus helveticus R0052 and Lactobacillus rhamnosus R0011) or a placebo for 6 months. Subjects were randomly assigned into four intervention groups: influenza vaccine and probiotics (n = 141), influenza vaccine and placebo (n = 136), placebo and probiotics (n = 140), and both placebo (n = 137). The primary outcome was ILI incidence within 6 months. The secondary outcomes were seroprotection and seroconversion rates at 1, 4, and 6 months after administering the interventions.ResultsThis study showed that the trivalent influenza vaccine increased seroprotection (RR 3.6 [95%CI 2.92–4.47]; p<0.010) and seroconversion (RR 29.8 [95%CI 11.1–79.5]; p<0.010) rates 1 month after vaccination in elderly people while the probiotic supplement did not alter influenza antibody titers (p = 1.000 and p = 0.210). The relative ILI incidence risk was similar between vaccinated and non-vaccinated groups, as well as in the probiotic group compared to the non-probiotic group.ConclusionThe tested trivalent influenza vaccine significantly induced seroprotection and seroconversion in the vaccinated subjects, while probiotics administration did not influence these parameters. Vaccinated individuals displayed a similarly low ILI incidence as those in the Control Group. However, the observed trend towards a reduction of ILI incidence with probiotics supplementation warrants further assessments in a larger, at-risk population.Clinical trial registry numberNCT03695432.

Подход к профилактике и лечению неалкогольной жировой болезни печени у детей с ожирением с позиции современных международных рекомендаций

Актуальность. Статья посвящена проблеме профилактики развития и терапии неалкогольной жировой болезни печени (НАЖБП) у детей с ожирением по алиментарно-конституциональному типу. Цель: изучение эффективности и безопасности использования препаратов омега-3 полиненасыщенных жирных кислот (ПНЖК) с витамином Е и мультипробиотического комплекса, обогащенного витаминами, для профилактики развития и прогрессирования стеатогепатоза. Материалы и методы. Под наблюдением находились 55 детей с избыточной массой тела. Всем пациентам была назначена медикаментозная терапия с использованием препарата омега-3 ПНЖК Рейтоил и комплексного пробиотика Бревелак (Lactobacillus helveticus R0052, Lactococcus lactis ssp. Lactis R1058, Bifidobacterium longum R0175, Lactobacillus rhamnosus R0011, Bifidobacterium breve R0070, Streptococcus thermophilus R0083, Bifidobacterium bifidum R0071, Lactobacillus casei R0215, Lactobacillus plantarum R1012) на фоне модификации образа жизни. Результаты. Течение НАЖБП у детей в большинстве случаев не имеет характерной клинической симптоматики и выраженного синдрома цитолиза. Структурно-функциональные изменения в печени при НАЖБП могут вызывать метаболические нарушения с формированием выраженной атерогенной дислипидемии. Трехмесячный курс терапии НАЖБП препаратами омега-3 ПНЖК Рейтоил в сочетании с использованием комплексного пробиотического препарата Бревелак показал достоверное снижение активности печеночных цитолитических ферментов и улучшение показателя липидного спектра крови. Выводы. Назначение препаратов омега-3 ПНЖК в сочетании с комплексом штаммов пробиотических культур с доказанной клинической эффективностью при НАЖБП на фоне модификации образа жизни способствует эффективной профилактике и лечению данной патологии у детей.

The Efficacy, Safety, and Tolerability of Probiotics on Depression: Clinical Results From an Open-Label Pilot Study.

Background: A growing body of research has shown that consumption of probiotics can improve symptoms associated with mood and anxiety disorders through activity of the gut-brain axis. However, the effects of probiotics have yet to be tested in a clinical sample of treatment-naïve patients diagnosed with Major Depressive Disorder (MDD). The aim of this 8-week, open-label pilot study is to examine changes in depressive symptoms before and after the introduction of a probiotic supplement in 10 treatment-naïve MDD patients and to provide data on the feasibility of conducting a larger double-blind, randomized, placebo-controlled trial in the same patient population. Here we report on the clinical outcome measures of the study.Methods: Participants recruited from the community in Kingston, Ontario, Canada consumed a probiotic supplement containing Lactobacillus helveticus R0052 and Bifidobacterium longum R0175 (CEREBIOME®) at a dose of 3 × 109 CFU once per day for 8 weeks. Clinical symptoms of depression were measured using a validated battery of clinical scales and self-report questionnaires (CAN-BIND protocol). Data was collected at baseline, week 4, and week 8.Results: Significant improvements in affective clinical symptoms were observed at week 4 and were sustained at week 8. Significant improvements in subjective sleep quality were observed by week 8. No side effects or adverse effects associated with the probiotic supplement were observed.Conclusions: The findings from this study support the existing evidence in this emerging field for probiotics having a role in alleviating symptoms of depression in treatment-naïve, moderately depressed patients and indicate that the probiotic supplement is safe and well-tolerated in this population. However, further comprehensive studies are required to draw conclusions.

Supplementation with Combined Lactobacillus helveticus R0052 and Bifidobacterium longum R0175 Across Development Reveals Sex Differences in Physiological and Behavioural Effects of Western Diet in Long-Evans Rats.

The gut microbiome affects various physiological and psychological processes in animals and humans, and environmental influences profoundly impact its composition. Disorders such as anxiety, obesity, and inflammation have been associated with certain microbiome compositions, which may be modulated in early life. In 62 Long–Evans rats, we characterised the effects of lifelong Bifidobacterium longum R0175 and Lactobacillus helveticus R0052 administration—along with Western diet exposure—on later anxiety, metabolic consequences, and inflammation. We found that the probiotic formulation altered specific anxiety-like behaviours in adulthood. We further show distinct sex differences in metabolic measures. In females, probiotic treatment increased calorie intake and leptin levels without affecting body weight. In males, the probiotic seemed to mitigate the effects of Western diet on adult weight gain and calorie intake, without altering leptin levels. The greatest inflammatory response was seen in male, Western-diet-exposed, and probiotic-treated rats, which may be related to levels of specific steroid hormones in these groups. These results suggest that early-life probiotic supplementation and diet exposure can have particular implications on adult health in a sex-dependent manner, and highlight the need for further studies to examine the health outcomes of probiotic treatment in both sexes.

Effects of a Psychobiotic Supplement on Serum Brain-derived Neurotrophic Factor Levels in Depressive Patients: A Post Hoc Analysis of a Randomized Clinical Trial.

Background/AimsPsychobiotics are probiotics or prebiotics that, upon ingestion in adequate amounts, yield positive influence on mental health via microbiota-gut-brain axis regulation to modulate the circulating cytokines, chemokines, neurotransmitters, or neurotrophins levels. We have recently shown that a psychobiotic combination (Lactobacillus helveticus R0052 and Bifidobacterium longum R0175; CEREBIOME) significantly improved depression symptoms in patients with depression. Recent animal data suggest the influence of the gut microbiota on brain-derived neurotrophic factor (BDNF), which was shown to correlate with antidepressant response in depressive patients. Therefore, we conducted this exploratory post hoc analysis of BDNF levels to clarify the mechanism of action of this psychobiotic in our cohort.MethodsOur study was a double-blind, randomized controlled trial of patients with low-to-moderate depression receiving either a probiotic combination, prebiotic or placebo. From the 110 patients randomized in the trial, 78 were included in this post hoc analysis (probiotic, n = 28; prebiotic and placebo, n = 25). We compared serum BDNF levels from participants at baseline and endpoint, and assessed the Pearson correlation between depression severity and BDNF levels for each intervention.ResultsWe found that post-intervention BDNF levels were significantly different between groups (P < 0.001). Furthermore, BDNF levels increased significantly in the probiotic group compared to both the prebiotic (P < 0.001) and placebo groups (P = 0.021), which inversely correlated with depression severity compared to placebo (ANOVA/ANCOVA, P = 0.012; Pearson, r = –0.79, P < 0.001). In the prebiotic group, BDNF levels reduced but not significantly compared with placebo group (P > 0.05).ConclusionEight-week supplementation with B. longum and L. helveticus in depressive patients improved depression symptoms, possibly by increasing BDNF levels.

Safety and Effect of a Low- and High-Dose Multi-Strain Probiotic Supplement on Microbiota in a General Adult Population: A Randomized, Double-Blind, Placebo-Controlled Study

Few studies have focused on dose-response analyses of multi-strain probiotics in the general adult population. This study aimed at comparing how a low- and high-dose of a multi-strain probiotic supplement (containing Lactobacillus helveticus R0052, Lactobacillus rhamnosus R0011, Lactobacillus casei R0215, Pediococcus acidilactici R1001, Bifidobacterium breve R0070, Bifidobacterium longum ssp. longum BB536, Lactobacillus plantarum R1012, Lactococcus lactis ssp. lactis R1058) affected microbiota composition, transit persistence and safety in adults. After a 7-d baseline, participants were randomized to receive capsules containing 5 or 25 billion CFU, or placebo daily for 28 days, followed by a 7-d washout. Digestive health and general wellness were assessed. Fecal microbiota composition was analyzed using 16S rRNA gene amplicon sequencing and strain persistence, by qPCR. Participants’ gastrointestinal and general wellbeing were unaffected. No adverse events were associated with either dose. Supplemented strains contributed to the Lactobacillus and Bifidobacterium genera detected in stool, with 0.40 ± 0.11% and 0.51 ± 0.26%, respectively, in the high-dose group. Strain-specific qPCR assays revealed variable levels of post-intervention persistence between strains. Sequencing and composition analyses using the 16S V4 region revealed a decrease in Holdemania and increase in Bacteroidales. The formulation was well tolerated in this sample of the general adult population, even at the higher dose. The strains appear to have influenced microbiota composition minimally, as expected in the absence of dysbiosis, and consistently with the dose administered. Overall, the results provide a rationale to study the effects this formulation on microbiota composition in individuals exhibiting dysbiosis associated with metabolic disorders or obesity.

Strain-Specific Probiotic Properties of Bifidobacteria and Lactobacilli for the Prevention of Diarrhea Caused by Rotavirus in a Preclinical Model.

Probiotic supplementation with different lactobacilli and bifidobacterial strains has demonstrated beneficial effects in infectious diarrhea caused by rotavirus (RV) in young children. Preclinical models of RV infection might be a good strategy to screen for the efficacy of new probiotic strains or to test their comparative efficacy. Neonatal Lewis rats were supplemented with Bifidobacterium breve M-16V, Lactobacillus acidophilus NCFM, Lactobacillus helveticus R0052, or Lactobacillus salivarius PS2 from days 2–14 of life. On day five, animals received RV SA-11 orally. Fecal samples were collected daily, weighed, and scored for the calculation of severity and incidence of diarrhea. In addition, fecal pH and fecal viral shedding were measured. Animals were sacrificed at the end of the study and their blood was obtained for the quantification of RV-specific immunoglobulins. RV infection was induced in ~90% of the animals. All probiotics caused a reduction of several clinical variables of severity and incidence of diarrhea, except L. salivarius PS2. L. acidophilus NCFM, B. breve M-16V, and L. helveticus R0052 seemed to be very effective probiotic strains. In addition, all Lactobacillus strains reduced the viral elimination one day post-inoculation. No differences were detected in the specific anti-RV humoral response. The present study highlights the strain-specific effects of probiotics and identifies promising probiotics for use in ameliorating and preventing RV-induced diarrhea in children, for example by including them in infant formulas.

Lactobacillus helveticus R0052 alleviates liver injury by modulating gut microbiome and metabolome in D-galactosamine-treated rats.

The liver is an important digestive gland, and acute liver failure results in high mortality. Probiotics are considered potential adjuvant therapies for liver disease. This study aimed to investigate the beneficial effects of Lactobacillus helveticus R0052 on acute liver injury and the underlying mechanisms. Sprague-Dawley rats were gavaged with L. helveticus R0052 suspensions (3 × 109 CFU) for 1 week. Subsequently, acute liver injury was induced by intraperitoneal D-galactosamine injection on the eighth day. After 24 h, samples (blood, liver, ileum, faeces) were collected and assessed for histological injury, inflammation, intestinal barrier, gut microbiome and metabolome. L. helveticus R0052 alleviated aminotransferase, bilirubin and total bile acid elevation and histological hepatic injuries. Additionally, L. helveticus R0052 exhibited anti-inflammatory properties by downregulating Toll-like receptors, tumour necrosis factor-α and nuclear factor-κb transcription in liver samples and decreasing proinflammatory cytokine plasma concentrations. Additionally, L. helveticus R0052 ameliorated intestinal abnormalities and regulated Toll-like receptors, claudin2 and mucin3 gene transcription in the intestine. These effects were associated with gut microbiome and metabolome modulation by L. helveticus R0052. Probiotic pretreatment enriched Lactobacillus and Bacteroides and depleted Flavonifractor and Acetatifactor in the gut microbiome. Meanwhile, L. helveticus R0052 improved carbohydrate and fatty acid metabolism and reduced lithocholic acid levels. These results indicate that L. helveticus R0052 is promising for alleviating acute liver injury and provide new insights regarding the correlations among the microbiome, the metabolome, the intestinal barrier and liver disease.