Oral Bacteriotherapy Research Articles

Probiotics by Modulating Gut-Brain Axis Together With Brivaracetam Mitigate Seizure Progression, Behavioral Incongruities, and Prevented Neurodegeneration in Pentylenetetrazole-Kindled Mice.

The microbiota-gut-brain axis (MGBA) is a central nexus that integrates higher cognitive and emotional centers of the central nervous system (CNS) within the intricate functioning of the intestine. Accumulating evidence suggests that dysbiosis in the taxonomic diversity of gut flora plays a salient role in the progression of epilepsy and comorbid secondary complications. In the current study, we investigated the impact of long-term oral bacteriotherapy (probiotics; 10 mL/kg; 109 colony-forming unit/ml) as an adjunctive treatment intervention with brivaracetam (BRV; 10 mg/kg) over 21 days on pentylenetetrazole (PTZ) induced augmented epileptic response and associated electrographical and behavioral perturbations in mice. Moreover, we also unveiled antioxidant capacity and histopathologic changes in treated versus non-treated animals. Results revealed combination increases seizure threshold and prevented high ictal spiking. Additionally, it alleviated PTZ-induced neuropsychiatric disturbances such as anxiety and depressive-like phenotype along with cognitive deficits. Furthermore, dual therapy prompted physiological oxidant/antioxidant balance as evidenced by increased activity of antioxidant enzymes (SOD and catalase) and reduced levels of oxidative stressor (MDA). This therapeutic intervention with commensal species suppressed network-driven neuroinflammation and preserved normal cytoarchitecture with intact morphology in the pyramidal layers of cornu ammonis (CA1 and CA3). Our study provides supporting evidence for the use of probiotics as adjunctive therapy with anti-seizure medications to modulate epileptogenic processes and related multimorbidities, particularly in individuals with drug-resistant seizures.

Oral bacteriotherapy is associated with decreased blood lactate concentration during exercise at high altitude

Exposure to high altitude leads to decreased oxygen saturation (SpO2) and, in some individuals, the development of adverse outcomes such as acute high-altitude sickness. A further decrease in oxygen availability during exercise at altitude leads to greater anaerobic metabolism and increased lactate production. Previous studies show that ingestion of the probiotic SLAB51 (O2BOOSTER; Hecto, Seoul, South Korea) improved SpO2 in individuals exercising in a hypobaric chamber (simulated altitude 16,732 ft (~5100 m) above sea level) compared to individuals who did not ingest the probiotic. However, the use of SLAB51 during exercise at high terrestrial altitude has yet to be studied. We hypothesized that individuals who ingest SLAB51, relative to those given a placebo, will exhibit less of a difference in lactate production during sub-maximal exercise when paired high-altitude and sea-level values pre- and post-exercise are compared. We recruited 17 participants of Latino ancestry, ages 19-63 years, for studies at sea level (University of California, San Diego) and at high altitude (University of California White Mountain Barcroft Research Station, 3801 m). At sea level and on the third or fourth day at high altitude, we measured SpO2 and heart rate (HR) via pulse oximetry (forehead probe) before and during the last 30 seconds of a 10-minute submaximal (1 watt/kg) bout of exercise on a cycle ergometer (n = 5 for each group). Blood lactate concentration was measured before and after exercise from fingertip capillary blood samples. The respective differences between SpO2 and HR pre-exercise and during the final 30 seconds of exercise (the ΔSpO2 and ΔHR) were calculated for all individuals. The Δlactate blood concentration was calculated by the difference between lactate pre- and post-exercise. ΔSpO2, ΔHR, and Δlactate values were computed for sea level and high altitude. The difference between the respective sea-level Δ and the high-altitude Δ values were quantified for each measurement and compared between the groups who received either SLAB51 or the placebo upon arrival, and the same treatment for three days at high altitude. As expected, exercise increased HR and blood lactate concentration at sea level and high altitude and decreased SpO2 at high altitude. The difference of Δlactate between sea level and high altitude was lower (p = 0.023) in the SLAB51 (n = 4, 0.93 ± 0.18 mmol/L) versus placebo (n = 4, 1.63 ± 0.13 mmol/L) group. However, there were no significant differences of ΔSpO2 and ΔHR between groups. Our findings show that taking SLAB51 could lower the production of lactate during submaximal exercise at high altitude. This means that anaerobic glycolysis may play a smaller role in energy production when the probiotic is taken compared to the placebo. To further understand the influence of SLAB51 as a supplement on exercise performance at altitude, more research with a bigger sample size is necessary. Supported by LEA Altitude Performance Fund. This is the full abstract presented at the American Physiology Summit 2024 meeting and is only available in HTML format. There are no additional versions or additional content available for this abstract. Physiology was not involved in the peer review process.

GBA-related diseases and the application in Tourette syndrome treatment

This paper discusses the gut-brain axis (GBA) and how it takes part in various neurological diseases, including Alzheimers disease (AD), Attention-deficit hyperactivity disorder (ADHD), and Tourette syndrome. The gut microbiota, inducing vital communications with the brain through the GBA, is not to be neglected in maintaining physiological balance, with the potential to become a source of new therapeutic opportunities for treating these diseases. Current studies show that methods such as personalized diets, oral bacteriotherapy, and multi-strain probiotics like SLAB51 and DEX have promising results in treating AD and ADHD through manipulation of the biotas. Based on the analysis of previous research, this paper finds how changes in gut microbiota amount in feces between healthy and TS mice, in particular the decrease in Firmicutes and Actinobacteria, and the increase in Bacteroidetes and Proteobacteria. However, future studies and experiments are required to evaluate potential side effects of microbiome alterations in humans, and potential treatments for Tourettes syndrome based on gut microbiota analysis. The GBA is a promising area for developing new therapeutic approaches for neurological diseases, and future research in this field holds great potential for advancements in the treatment of these disorders currently with no verified cures.

Efficacy of Lactococcus lactis strain Plasma on clearance of anal HPV infection in men who have sex with men: A single-center, double-blinded, randomized placebo-controlled trial (CLEAR HPV study)

Background: Anal cancer is a human papillomavirus-related cancer; specifically, it is preceded by high-grade squamous intraepithelial lesions, which are less likely to regress spontaneously than low-grade intraepithelial lesions. Although most human papillomavirus (HPV) infections are thought to clear spontaneously, anal HPV infection persists, especially in people living with HIV. Preliminary results from a recent small randomized placebo-controlled trial of oral bacteriotherapy using a high dose of probiotics demonstrated clearance of anal high-risk HPV (hr-HPV) infection and lower onset of new high-grade squamous intraepithelial lesions among people living with HIV. Lactococcus lactis strain Plasma is a lactic acid bacterium directly activating plasmacytoid dendritic cells and inducing release of type I and III interferons via Toll-like receptor 9 stimulation. Based on these findings, oral bacteriotherapy with LC-plasma may contribute to clearing anal hr-HPV infection and reducing anal precancerous lesions by activating innate and acquired immune responses. This randomized placebo-controlled trial aims to investigate the efficacy and safety of LC-plasma therapy in clearing anal hr-HPV infection and reducing anal precancerous lesions among men who have sex with men with or without HIV infection. Methods: Participants with anal hr-HPV infection will be included and receive test capsules. A total of 150 patients will be included in the intervention group with follow-up, which will consist of HPV genotype test, cytology by anal pap smear, and biopsy with high-resolution anoscopy. The primary endpoint will be the clearance rate of the hr-HPV genotype infection at the anal site at 180 days. The secondary endpoints will be changes in anal epithelial neoplasia detected using high-resolution anoscopy at 180 days; change in abnormal cytology by anal pap smear at 180 days; change in hr-HPV genotype at the anal site at 180 days; change or percentage change in peripheral blood CD4 positive T-lymphocyte numbers in HIV-infected participants at 180 days; changes in quantitative hepatitis B surface antigen levels at 180 days in the HBV-infected participants; and adherence to the study drugs. Conclusion: This randomized controlled study will provide data on the efficacy and safety of LC-plasma as a treatment for anal HPV infection and grade 2 or 3 anal intraepithelial neoplasia.

Lactic Acid Bacteria (LAB) and Neuroprotection, What Is New? An Up-To-Date Systematic Review.

In recent years, the potential role of probiotics has become prominent in the discoveries of neurotherapy against neurodegenerative diseases, such as Alzheimer's and Parkinson's diseases. Lactic acid bacteria (LAB) exhibit neuroprotective properties and exert their effects via various mechanisms of actions. This review aimed to evaluate the effects of LAB on neuroprotection reported in the literature. A database search on Google Scholar, PubMed, and Science Direct revealed a total of 467 references, of which 25 were included in this review based on inclusion criteria which comprises 7 in vitro, 16 in vivo, and 2 clinical studies. From the studies, LAB treatment alone or in probiotics formulations demonstrated significant neuroprotective activities. In animals and humans, LAB probiotics supplementation has improved memory and cognitive performance mainly via antioxidant and anti-inflammatory pathways. Despite promising findings, due to limited studies available in the literature, further studies still need to be explored regarding synergistic effects, efficacy, and optimum dosage of LAB oral bacteriotherapy as treatment or prevention against neurodegenerative diseases.

The crosstalk between gut barrier impairment, mitochondrial dysfunction, and microbiota alterations in people living with HIV.

Functional and structural damage of the intestinal mucosal barrier significantly contribute to translocation of gut microbial products into the bloodstream and are largely involved in HIV-1 associated chronic immune activation. This microbial translocation is largely due to a progressive exhaustion of intestinal macrophage phagocytic function, which leads to extracellular accumulation of microbial derived components and results in HIV-1 disease progression. This study aims to better understand whether the modulation of gut microbiota promotes an intestinal immune restoration in people living with HIV (PLWH).Long-term virologically suppressed PLWH underwent blood, colonic, and fecal sampling before (T0) and after 6 months (T6) of oral bacteriotherapy. Age- and gender-matched uninfected controls (UC) were also included. 16S rRNA gene sequencing was applied to all participants'fecal microbiota. Apoptosis machinery, mitochondria, and apical junctional complex (AJC) morphology and physiological functions were analyzed in gut biopsies.At T0, PLWH showed a different pattern of gut microbial flora composition, lower levels of occludin (p = 0.002)and zonulin (p = 0.01), higher claudin-2 levels (p = 0.002), a reduction of mitochondria number (p = 0.002), and diameter (p = 0.002), as well as increased levels of lipopolysaccharide(LPS) (p = 0.018) and cCK18 (p = 0.011), compared to UC. At T6, an increase in size (p = 0.005) and number (p = 0.008) of mitochondria, as well as amelioration in AJC structures (p < 0.0001) were observed. Restoration of bacterial richness (Simpson index) and biodiversity (Shannon index) was observed in all PLWH receiving oral bacteriotherapy (p < 0.05). Increased mitochondria size (p = 0.005) and number (p = 0.008) and amelioration of AJC structure (p < 0.0001) were found at T6 compared to T0. Moreover, increased occludin and zonulin concentration were observed in PLWH intestinal tracts and decreased levels of claudin-2, LPS, and cCK18 were found after oral bacteriotherapy (T0 vs. T6, p < 0.05 for all these measures).Oral bacteriotherapy supplementation might restore the balance of intestinal flora and support the structural and functional recovery of the gut mucosa in antiretroviral therapy treated PLWH.

Exploiting Bacteria for Improving Hypoxemia of COVID-19 Patients.

Background: Although useful in the time-race against COVID-19, CPAP cannot provide oxygen over the physiological limits imposed by severe pulmonary impairments. In previous studies, we reported that the administration of the SLAB51 probiotics reduced risk of developing respiratory failure in severe COVID-19 patients through the activation of oxygen sparing mechanisms providing additional oxygen to organs critical for survival. Methods: This “real life” study is a retrospective analysis of SARS-CoV-2 infected patients with hypoxaemic acute respiratory failure secondary to COVID-19 pneumonia undergoing CPAP treatment. A group of patients managed with ad interim routinely used therapy (RUT) were compared to a second group treated with RUT associated with SLAB51 oral bacteriotherapy (OB). Results: At baseline, patients receiving SLAB51 showed significantly lower blood oxygenation than controls. An opposite condition was observed after 3 days of treatment, despite the significantly reduced amount of oxygen received by patients taking SLAB51. At 7 days, a lower prevalence of COVID-19 patients needing CPAP in the group taking probiotics was observed. The administration of SLAB51 is a complementary approach for ameliorating oxygenation conditions at the systemic level. Conclusion: This study proves that probiotic administration results in an additional boost in alleviating hypoxic conditions, permitting to limit on the use of CPAP and its contraindications.

Oral Bacteriotherapy Reduces the Occurrence of Chronic Fatigue in COVID-19 Patients.

Long COVID refers to patients with symptoms as fatigue, “brain fog,” pain, suggesting the chronic involvement of the central nervous system (CNS) in COVID-19. The supplementation with probiotic (OB) would have a positive effect on metabolic homeostasis, negatively impacting the occurrence of symptoms related to the CNS after hospital discharge. On a total of 58 patients hospitalized for COVID-19, 24 (41.4%) received OB during hospitalization (OB+) while 34 (58.6%) taken only the standard treatment (OB–). Serum metabolomic profiling of patients has been performed at both hospital acceptance (T0) and discharge (T1). Six months after discharge, fatigue perceived by participants was assessed by administrating the Fatigue Assessment Scale. 70.7% of participants reported fatigue while 29.3% were negative for such condition. The OB+ group showed a significantly lower proportion of subjects reporting fatigue than the OB– one (p < 0.01). Furthermore, OB+ subjects were characterized by significantly increased concentrations of serum Arginine, Asparagine, Lactate opposite to lower levels of 3-Hydroxyisobutirate than those not treated with probiotics. Our results strongly suggest that in COVID-19, the administration of probiotics during hospitalization may prevent the development of chronic fatigue by impacting key metabolites involved in the utilization of glucose as well as in energy pathways.

Generation of Bacillus subtilis displaying alpha-toxin HlaH35LH48L fused with CotB and CotG, and studying the immune response in mice

Introduction: The Bacillus subtilis spore is considered to be a powerful vehicle for surface display and antigen delivery. Being safe and widely used for the purpose of oral bacteriotherapy in humans and animals, B. subtilis spore has potential in the domain of needle-free vaccine development. The spores themselves also behave as an adjuvant. This study aims to generate B. subtilis spores expressing mutant staphylococcal alpha-toxin HlaH35LH48L on the surface and to study their ability to evoke a specific immune response in mice. Methods: Vectors carrying the hlaH35LH48L gene fused with the coding genes of anchor proteins, cotB and cotG, were cloned in E. coli before being transformed into B. subtilis. The generation of the B. subtilis new strains via chromosomal integration was confirmed by PCR. Sporulation was observed under the microscope. The expression of the target protein on the spore surface was determined by sporeELISA. The level of IgG in the serum and IgA in the feces of Swiss mice were analyzed using ELISA to learn about the immune response against the B. subtilis spore administrated via the oral route. Results: The PCR products of an expected size on agarose gel electrophoresis showed successful integration, resulting in the construction of new B. subtilis strains BsHT2331 and BsHT2334. sporeELISA analysis detected a significant HlaH35LH48L expression on the spore surface. The BsHT2331 spores (CotB-HlaH35LH48L) triggered a constant increase in the IgG and IgA levels in mice after three doses as 5.5-fold and 2.5-fold higher than the pre-immunization, respectively (p-value &lt; 0.0001). Meanwhile, the group of mice orally administrated with BsHT2334 (CotG-HlaH35LH48L) showed a notable IgG titer but minor IgA response. Conclusion: The results concluded that the construction of two new strains BsHT2331 and BsHT2334 that used spore coat proteins CotB and CotG to display mutant alpha-toxin HlaH35LH48L on the B. subtilis spore surface was successful. It provided an assessment of the ability of B. subtilis spores to stimulate specific antibody production in mice.

Strategic Modification of Gut Microbiota through Oral Bacteriotherapy Influences Hypoxia Inducible Factor-1α: Therapeutic Implication in Alzheimer's Disease.

Dysbiosis contributes to Alzheimer’s disease (AD) pathogenesis, and oral bacteriotherapy represents a promising preventative and therapeutic opportunity to remodel gut microbiota and to delay AD onset and progression by reducing neuroinflammation and amyloid and tau proteins aggregation. Specifically, SLAB51 multi-strain probiotic formulation positively influences multiple neuro-chemical pathways, but exact links between probiotics oral consumption and cerebral beneficial effects remain a gap of knowledge. Considering that cerebral blood oxygenation is particularly reduced in AD and that the decreased neurovascular function contributes to AD damages, hypoxia conditioning represents an encouraging strategy to cure diseases of the central nervous system. In this work, 8-week-old 3xTg-AD and wild-type mice were chronically supplemented with SLAB51 to evaluate effects on hypoxia-inducible factor-1α (HIF-1α), a key molecule regulating host-microbial crosstalk and a potential target in neurodegenerative pathologies. We report evidence that chronic supplementation with SLAB51 enhanced cerebral expression of HIF-1α and decreased levels of prolyl hydroxylase 2 (PHD2), an oxygen dependent regulator of HIF-1α degradation; moreover, it successfully counteracted the increase of inducible nitric oxide synthase (iNOS) brain expression and nitric oxide plasma levels in AD mice. Altogether, the results demonstrate an additional mechanism through which SLAB51 exerts neuroprotective and anti-inflammatory effects in this model of AD.

Clinical Effects of Oral Bacteriotherapy on Anal HPV Infection and Related Dysplasia in HIV-Positive MSM: Results from the "HPVinHIV" Trial.

Background. Anal HPV infection, anal dysplasia and, ultimately, anal cancer are particularly common in HIV-infected men who have sex with men. Treatment of anal dysplasia, aiming to prevent evolution to squamous cell carcinoma of the anus, is currently limited to direct ablation and/or application of topical therapy. The aim of the present study is to investigate the effect of oral bacteriotherapy (Vivomixx® in EU, Visbiome® in USA) on anal HPV infection and HPV-related dysplasia of the anal canal in HIV-infected men who have sex with men. Methods. In this randomized, placebo-controlled, quadruple-blinded trial (NCT04099433), HIV-positive men who have sex with men with anal HPV infection and HPV-related dysplasia were randomized to receive oral bacteriotherapy or placebo for 6 months. Anal HPV test, anal cytology and high resolution anoscopy with biopsies of anal lesions were performed at baseline and at the end of the study. Safety and tolerability of oral bacteriotherapy were also evaluated. Interim analysis results were presented. Results. 20 participants concluded the study procedures to date. No serious adverse events were reported. In respect to participants randomized to placebo, individuals in the experimental arm showed higher rate of anal dysplasia regression (p = 0.002), lower rate of onset of new anal dysplasia (p = 0.023) and lower rates of worsening of persistent lesions (p = 0.004). Clearance of anal HPV infection was more frequently observed in the bacteriotherapy group (p = 0.067). Conclusion. Being an interim analysis, we limit ourselves to report the preliminary results of the current study. We refer the conclusions relating to the possible effectiveness of the intervention to the analysis of the definitive data.

Oxygen Sparing Effect of Bacteriotherapy in COVID-19.

Background: We previously reported that severe COVID-19 patients had higher chances of survival and a reduced risk of developing respiratory failure when administered with the probiotic formulation SLAB51. This study aimed to investigate further bacteriotherapy mechanisms and how early they are activated. Methods: We performed an analysis on the blood oxygenation parameters collected in sixty-nine severe COVID-19 patients requiring non-invasive oxygen therapy and presenting a CT lung involvement ≥50%. Twenty-nine patients received low-molecular-weight heparin, azithromycin and Remdesivir. In addition, forty subjects received SLAB51. Blood gas analyses were performed before the beginning of treatments and at 24 h. Results: The patients receiving only standard therapy needed significantly increased oxygen amounts during the 24 h observation period. Furthermore, they presented lower blood levels of pO2, O2Hb and SaO2 than the group also supplemented with oral bacteriotherapy. In vitro data suggest that SLAB51 can reduce nitric oxide synthesis in intestinal cells. Conclusions: SARS-CoV-2 infected patients may present lesions in the lungs compromising their gas exchange capability. The functionality of the organs essential for these patients’ survival depends mainly on the levels of pO2, O2Hb and SaO2. SLAB51 contains enzymes that could reduce oxygen consumption in the intestine, making it available for the other organs.

Oral Bacteriotherapy in Patients With COVID-19: A Retrospective Cohort Study.

Background: Mounting evidence suggests SARS-CoV-2 may impact on host microbiota and gut inflammation, infecting intestinal epithelial cells. This possible link and its implications can be investigated by observing the effects of modulation of the microbial flora in patients with COVID-19. The aim of this study was to compare the rate of mortality, the need of ICU hospitalization and the length of hospitalization in patients with severe COVID-19 pneumonia who received the best available therapy (BAT) vs. patients treated with BAT and supplemented with oral bacteriotherapy.Methods: This retrospective, observational cohort study included 200 adults with severe COVID-19 pneumonia. All patients received therapeutic regimens including low molecular weight heparin plus one or more between hydroxychloroquine, azithromycin, antivirals, and Tocilizumab. Oral bacteriotherapy was used as complementary treatment.Results: Out of the 200 patients, 112 received BAT without oral bacteriotherapy, and 88 BAT with oral bacteriotherapy. Crude mortality was 22%. Eleven percent died in the group of patients treated with BAT plus oral bacteriotherapy vs. 30% subjects in the group of patients managed only with BAT (p < 0.001). By multivariate analysis, the age >65 years, CRP >41.8 mg/L, Platelets <150.000 mmc, and cardiovascular events were associated with the increased risk of mortality. Oral bacteriotherapy was an independent variable associated with a reduced risk for death. Despite large prospective trials are needed, this study highlights a possible role for oral bacteriotherapy in the management of patients hospitalized for COVID-19 pneumonia.

Microbiota modulation as preventative and therapeutic approach in Alzheimer’s disease

The gut microbiota coevolves with its host, and numerous factors like diet, lifestyle, drug intake and geographical location continuously modify its composition, deeply influencing host health. Recent studies demonstrated that gut dysbiosis can alter normal brain function through the so-called gut-brain axis, a bidirectional communication network between the central nervous system and the gastrointestinal tract, thus playing a key role in the pathogenesis of neurodegenerative disorders, such as Alzheimer's disease (AD). In this perspective, in the constant search for novel treatments in AD, the rational modulation of gut microbiota composition could represent a promising approach to prevent or delay AD onset or to counteract its progression. Preclinical and human studies on microbiota modulation through oral bacteriotherapy and faecal transplantation showed anti-inflammatory and antioxidant effects, upregulation of plasma concentration of neuroprotective hormones, restoration of impaired proteolytic pathways, amelioration of energy homeostasis with consequent decrease of AD molecular hallmarks and improvement of behavioural and cognitive performances. In this review, we dissect the role of gut microbiota in AD and highlight recent advances in the development of new multitarget strategies for microbiota modulation to be used as possible preventative and therapeutic approaches in AD.

Challenges in the Management of SARS-CoV2 Infection: The Role of Oral Bacteriotherapy as Complementary Therapeutic Strategy to Avoid the Progression of COVID-19.

Background: Gastrointestinal disorders are frequent in COVID-19 and SARS-CoV-2 has been hypothesized to impact on host microbial flora and gut inflammation, infecting intestinal epithelial cells. Since there are currently no coded therapies or guidelines for treatment of COVID-19, this study aimed to evaluate the possible role of a specific oral bacteriotherapy as complementary therapeutic strategy to avoid the progression of COVID-19.Methods: We provide a report of 70 patients positive for COVID-19, hospitalized between March 9th and April 4th, 2020. All the patients had fever, required non-invasive oxygen therapy and presented a CT lung involvement on imaging more than 50%. Forty-two patients received hydroxychloroquine, antibiotics, and tocilizumab, alone or in combination. A second group of 28 subjects received the same therapy added with oral bacteriotherapy, using a multistrain formulation.Results: The two cohorts of patients were comparable for age, sex, laboratory values, concomitant pathologies, and the modality of oxygen support. Within 72 h, nearly all patients treated with bacteriotherapy showed remission of diarrhea and other symptoms as compared to less than half of the not supplemented group. The estimated risk of developing respiratory failure was eight-fold lower in patients receiving oral bacteriotherapy. Both the prevalence of patients transferred to ICU and mortality were higher among the patients not treated with oral bacteriotherapy.Conclusions: A specific bacterial formulation showed a significant ameliorating impact on the clinical conditions of patients positive for SARS-CoV-2 infection. These results also stress the importance of the gut-lung axis in controlling the COVID-19 disease.

Modulation of Phenylalanine and Tyrosine Metabolism in HIV-1 Infected Patients with Neurocognitive Impairment: Results from a Clinical Trial.

To investigate the effects of oral bacteriotherapy on intestinal phenylalanine and tyrosine metabolism, in this longitudinal, double-arm trial, 15 virally suppressed HIV+ individuals underwent blood and fecal sample collection at baseline and after 6 months of oral bacteriotherapy. A baseline fecal sample was collected from 15 healthy individuals and served as control group for the baseline levels of fecal phenylalanine and tyrosine. CD4 and CD8 immune activation (CD38+) was evaluated by flow cytometry. Amino acid evaluation on fecal samples was conducted by Proton Nuclear Magnetic Resonance. Results showed that HIV+ participants displayed higher baseline phenylalanine/tyrosine ratio values than healthy volunteers. A significand reduction in phenylalanine/tyrosine ratio and peripheral CD4+ CD38+ activation was observed at the end of oral bacteriotherapy. In conclusion, probiotics beneficially affect the immune activation of HIV+ individuals. Therefore, the restoration of intestinal amino acid metabolism could represent the mechanisms through which probiotics exert these desirable effects.

Anti-microbial susceptibility pattern of spores used in Bacillus clausii suspension: an in vitro study

Background: Bacillus species have been used as probiotics as they have high stability to gastrointestinal conditions and impart health benefit on the host. Primarily used in their spore form the diversity of Bacillus species being used and their applications are remarkable. Here, we present the results of the antimicrobial susceptibility testing of the B. clausii spore suspension (Benegut®).Methods: Bacillus clausii spore suspension (Benegut®), used in oral bacteriotherapy was tested for the susceptibility to therapeutically useful antibiotics. Twelve commercially prepared, paper antibiotic discs of different drugs having fixed concentrations were used. The antimicrobial susceptibility test was performed by the disc diffusion technique, using soybean casein digestive agar (SCDA) as media and the results were categorized as susceptible, intermediate, or resistant; using the criteria published by the Clinical and Laboratory Standards Institute.Results: B. clausii was found to be resistant to broad-spectrum antibiotic chloramphenicol, antimycobacterial rifampicin, beta-lactamase inhibitor amoxiclav, first-generation antibiotic cefaloridine, penicillin ampicillin, and tetracycline. B. clausii was resistant to both the aminoglycoside antibiotics (streptomycin and kanamycin) studied. Off first-generation fluoroquinolones studied, B. clausii was resistant to ciprofloxacin but partially sensitive to norfloxacin, ofloxacin and to macrolide azithromycin. Conclusions: Antimicrobial resistance is an important feature of probiotics. The results of our study indicate that the antimicrobial and immunomodulatory activity B. clausii spore suspension (Benegut®) can profess beneficial effects and can be a useful source of improving the intestinal imbalance of microbial flora and is safe for human consumption.

Application of Oral Bacteriotherapy to Promote Anal HPV Clearance in HIV Positive Individuals

Application of Oral Bacteriotherapy to Promote Anal HPV Clearance in HIV Positive Individuals

Effect of probiotic supplementation on seizure activity and cognitive performance in PTZ-induced chemical kindling

Epilepsy is one of the most common neurological disorders that severely affect life quality of many people worldwide. Ion transport in the neuronal membrane, inhibitory–excitatory mechanisms, and regulatory modulator systems have been implicated in the pathogenesis of epilepsy. A bidirectional communication is proposed between brain and gut where the brain modulates the gastrointestinal tract, and the gut can affect brain function and behavior. The gut microbiome takes an important role in health and disease where dysbiosis is involved in several neurological disorders. Probiotics as living microorganisms are beneficial to humans and animals when adequately administered. In the present work, we evaluated the effect of a probiotic bacteria mixture on seizure activity, cognitive function, and gamma-aminobutyric acid (GABA), nitric oxide (NO), malondealdehyde (MDA), and total antioxidant capacity (TAC) level of the brain tissue in the pentylenetetrazole (PTZ)-induced kindled rats. The Racine score and performance in water maze were considered as indices of the epileptic severity and the spatial learning and memory, respectively. We found that the probiotic supplementation substantially reduces seizure severity so that almost no probiotic-treated animals showed full kindling. The oral bacteriotherapy partially improved the spatial learning and memory in the kindled rats. The intervention decreased NO and MDA and increased TAC concentration of the brain. The probiotic treatment also increased the inhibitory neurotransmitter GABA. Our findings are the first preclinical report to show positive effect of probiotic bacteria on seizure-induced neurological disorders. Further investigation is required to answer the questions raised about the probable mechanisms involved.

The Effects of Probiotic Formulation Pretreatment (Lactobacillus helveticus R0052 and Bifidobacterium longum R0175) on a Lipopolysaccharide Rat Model

Objective: The role of gut microbiota in the pathogenesis of several neurodegenerative disorders, including Alzheimer’s disease (AD), via the gut–brain axis has recently been demonstrated; hence, modification of the intestinal microbiota composition by probiotic biotherapy could be a therapeutic target for these conditions. The aim of this study was to assess the effects of a probiotic formulation (Lactobacillus helveticus R0052 and Bifidobacterium longum R0175) on inflammatory and memory processes in lipopolysaccharide (LPS)-induced rats, one of the animal models used in peripherally induced neuroinflammation and neurodegeneration.Methods: Rats were randomly divided into four groups (Control, LPS, Probiotic + LPS, and Probiotic). All experimental groups were orally administrated maltodextrin (placebo) or probiotic (109 CFU/ml/rat) for 14 consecutive days and then were injected with saline or LPS (1 mg/kg, intraperitoneally [i.p.], single dose) 20 hours later. Memory retention ability and systemic and neuroinflammatory markers were assessed 4 hours after the injections.Results: Systemic exposure to LPS resulted in significant elevation of both the circulating and hippocampal levels of proinflammatory cytokines, which decreased remarkably following probiotic pretreatment. Oral bacteriotherapy with a combination of L. helveticus R0052 and B. longum R0175 also attenuated the decremental effect of LPS on memory through brain-derived neurotrophic factor (BDNF) expression at the molecular level; however, this effect was not significant in the passive avoidance test at the behavioral level.Conclusions: These results suggest that the management of gut microbiota with this probiotic formulation could be a promising intervention to improve neuroinflammation-associated disorders such as AD.