ResearchPad - probiotics https://www.researchpad.co Default RSS Feed en-us © 2020 Newgen KnowledgeWorks <![CDATA[Anti-cancer effects of <i>Bifidobacterium</i> species in colon cancer cells and a mouse model of carcinogenesis]]> https://www.researchpad.co/article/elastic_article_14495 Probiotics are suggested to prevent colorectal cancer (CRC). This study aimed to investigate the anticancer properties of some potential probiotics in vitro and in vivo.Materials and methodsAnticancer effects of potential probiotic groups were investigated following of in LS174T cancer cells compared to IEC-18 normal cells. 1. a single strain of Bifidobacterium. breve, 2. a single strain of Lactobacillus. reuteri, 3. a cocktail of 5 strains of Lactobacilli (LC), 4. a cocktail of 5 strains of Bifidobacteria (BC), 5. a cocktail of 10 strains from Lactobacillus and Bifidobacterium (L+B). Apoptosis rate, EGFR, HER-2 and PTGS-2 (COX-2 protein) expression levels were assessed as metrics of evaluating anticancer properties. Effect of BC, as the most effective group in vitro, was further assessed in mice models.ResultsBC induced ~21% and only ~3% apoptosis among LS174T and IEC-18 cells respectively. BC decreased the expression of EGFR by 4.4 folds, HER-2 by 6.7 folds, and PTGS-2 by 20 folds among the LS174T cells. In all these cases, BC did not interfere significantly with the expression of the genes in IEC-18 cells. This cocktail has caused only 1.1 folds decrease, 1.8 folds increase and 1.7 folds decrease in EGFR, HER-2 and PTGS-2 expression, respectively. Western blot analysis confirmed these results in the protein level. BC significantly ameliorated the disease activity index, restored colon length, inhibited the increase in incidence and progress of tumors to higher stages and grades.ConclusionsBC was the most efficient treatment in this study. It had considerable “protective” anti-cancer properties and concomitantly down regulated EGFR, HER-2 and PTGS-2 (COX-2), while having significant anti-CRC effects on CRC mice models. In general, this potential probiotic could be considered as a suitable nutritional supplement to treat and prevent CRC. ]]> <![CDATA[Prevention of excessive exercise‐induced adverse effects in rats with Bacillus subtilis BSB3]]> https://www.researchpad.co/article/N21a6bd10-3574-4603-adbe-c7c67bf2ab9b

Abstract

Aims

To characterize efficacy of the Bacillus subtilis BSB3 (BSB3) strain in the prevention of excessive exercise‐induced side effects and in maintaining stability of the gut microbiota.

Methods and Results

Rats were pretreated by oral gavage with B. subtilis BSB3 (BSB3) or with phosphate‐buffered saline (PBS) twice a day for 2 days, and were either exposed forced treadmill running or remained sedentary. Histological analysis of intestine, immunofluorescence staining of tight junction (TJ) proteins, serum lipopolysaccharide and intestinal fatty acid‐binding protein assay, culture‐based analysis and pyrosequencing for the gut microbiota were performed for each rat. Forced running resulted in a substantial decrease in intestinal villi height and total mucosa thickness, the depletion of Paneth cells, an inhibition of TJ proteins expression. Short‐term treatment of rats with BSB3 before running prevented these adverse effects. Culture‐based analysis of the gut microbiota revealed significant elevation of pathogenic microorganisms only in treadmill‐exercised rats pretreated with PBS. High‐throughput 16S rRNA gene sequencing also revealed an increase in pathobionts in this group. Preventive treatment of animals with BSB3 resulted in predominance of beneficial bacteria.

Conclusions

BSB3 prevents excessive exercise‐associated complications by beneficial modulation of the gut microbiota.

Significance and Impact of the Study

Our study shows a new application of beneficial bacteria for prevention the adverse effects of excessive exercise.

]]>
<![CDATA[Stages of pregnancy and weaning influence the gut microbiota diversity and function in sows]]> https://www.researchpad.co/article/Nd44aa2d8-25dc-4213-8fea-17f108069745

Abstract

Aims

The gut microbiota is believed to play important roles in the health of pregnant mammals, including their nutrient metabolism, immune programming and metabolic regulation. However, until recently, the shifts in gut microbiota composition and faecal and blood metabolic activity during different stages of pregnancy had not been investigated.

Methods and Results

We investigated the shifts in backfat thickness, plasma and faecal metabolites and gut microbiota on days 30, 60, 90 and 110 of pregnancy and on day 21 after parturition (weaning) in sows. The backfat thickness of sows did not significantly differ among the different stages of pregnancy. The plasma concentrations of lipid metabolites, including triacylglycerol (TG), total cholesterol, high‐density lipoprotein‐cholesterol, low‐density lipoprotein‐cholesterol and calcium were reduced (P < 0·05) during pregnancy. In addition, the concentration of these metabolites, except TG, reached their maximum at the time of weaning. We also found that Tenericutes, Fibrobacteres and Cyanobacteria varied significantly according to the stages of pregnancy in sows (P < 0·05). Most of the genera, such as Clostridiales, Desulfovibrio, Mogibacteriaceae and Prevotella, increased (P < 0·05) with the progression of pregnancy and decreased (P < 0·05) at weaning. The alpha diversity values (i.e., Shannon diversity and observed species) of sow gut microbiota increased (P < 0·05) from pregnancy to weaning. Pregnancy stages also significantly influenced (P < 0·05) the community structure (beta diversity) of gut microbiota. The progression of pregnancy was associated with changes in lipid metabolism and several carbohydrate‐degradation bacteria (i.e., Prevotella, Succinivibrio, Bacteroides and Parabacteroides).

Conclusions

Although causal links between the measured parameters remain hypothetical, these findings suggest that the increased diversity and concentration of beneficial gut microbes are associated with the metabolism of pregnant sows.

Significance and Impact of the Study

Manipulation of the sow gut microbiota composition may potentially influence metabolism and health during pregnancy.

]]>
<![CDATA[In vitro and ex vivo evaluation of the anti-Giardia duodenalis activity of the supernatant of Slab51 (SivoMixx)]]> https://www.researchpad.co/article/5c8acce0d5eed0c4849901f8

The effects on Giardia duodenalis of Slab51 probiotic supernatants were evaluated in vitro and ex vivo. In vitro, Slab51 (101 UFC) was cultured and the obtained supernatant was filtered, adjusted at pH 7, and added (100μl/ml) as such (Slab51 FS) or after heat-treatment, to G. duodenalis cultures to evaluate its effects on G. duodenalis trophozoites growth and adherence. For comparison, negative and metronidazole (20μg/ml) treated controls were used. The morphological and ultrastructural alterations of G. duodenals trophozoites following treatment with Slab51 FS supernatant were investigated by transmission electron microscopy. Ex vivo, mice duodenal portions were cultivated in standard conditions with 5x105 G. duodenalis trophozoites/ml, while to further five duodenal portions similarly cultured and infected, Slab51 FS 200μl was added. After 12 and 18h, samples were fixed in 10% buffered formalin and histologically processed to score Giardia infection and cell damage. Cell proliferation/apoptosis was scored by Ki67, TUNEL and Caspase–3 tests. All experiments were conducted in triplicate throughout the study. All data were statistically evaluated (P< 0.05). Results showed that Slab51 FS significantly reduced Giardia growth and adherence respect to negative controls, but its efficacy was overall lower than that of metronidazole. Moreover, the effects of Slab51 FS were significantly lowered by heat-treatment and this reduction was statistically higher at 90°C than at 56°C, indicating a heat-sensitive nature of active Slab51 FS compounds. At the ultrastructural level, Slab51 FS treated Giardia trophozoites were swelling, increased in size and showed alterations of their cellular membrane and vacuole patterns, loss of the nuclear envelope and nuclear architecture. In ex vivo trials, viable G. duodenalis trophozoites and enterocyte TUNEL+ and Caspase-3 expression were significantly reduced in intestinal sections added with Slab51 FS, while enterocyte Ki67 expression was significantly increased, confirming the anti-G. duodenalis activity of Slab51 FS observed in vitro. In conclusion, results from this study showed that the fresh culture supernatant of the commercial probiotic Slab51 has anti-G. duodenalis properties both in vitro and ex vivo in a mouse model.

]]>
<![CDATA[Effects of microbiota-driven therapy on inflammatory responses in elderly individuals: A systematic review and meta-analysis]]> https://www.researchpad.co/article/5c648cddd5eed0c484c81990

Current evidence suggests that age-associated inflammation, a strong risk factor for the health status of elderly individuals, is closely associated with gut microbiota. Previous animal studies have demonstrated a benefit of microbiota-driven therapy in decreasing low-grade chronic inflammation in elderly individuals; however, it remains controversial in clinical studies. Therefore, the present systematic review and meta-analysis were designed to assess the effects of microbiota-driven therapy on inflammatory markers in elderly individuals. PubMed, EMBASE, and the Cochrane Library were searched with no language restrictions from the inception of the database to November 11th, 2018 to identify all existing literature. We calculated pooled standard mean difference (SMD) using fixed effect model or random effect model to assess the effects of microbiota-driven therapy on elderly individuals. The methodological quality of the studies was determined according to the Cochrane Handbook. The publication bias was evaluated by funnel plot and Egger regression test. Ten randomized controlled studies, with 689 elderly individuals (347 individuals in the microbiota-driven therapy group and 342 individuals in the placebo group), were included in the analysis. Compared with placebo, microbiota-driven therapy did not decrease the levels of tumor necrosis factor-α (SMD, -0.24; 95% CI, -0.69 to 0.21; p = 0.30; I2 = 82.7%), interleukin-6 (SMD, -0.13; 95% CI, -0.74 to 0.49; p = 0.69; I2 = 90.7%) and interleukin-10 (SMD, 1.00; 95% CI, -0.15 to 2.15; p = 0.09; I2 = 96.3%). In addition, the microbiota-driven therapy also did not decrease the levels of C reactive protein (SMD, -1.28; 95% CI, -2.62 to 0.06; p = 0.06; I2 = 96.2%), interleukin-1β (SMD, -0.22; 95% CI, -0.81 to 0.37; p = 0.46; I2 = 73.8%), interleukin-8 (SMD, -0.03; 95% CI, -0.67 to 0.61; p = 0.93; I2 = 88.0%) and monocyte chemoattractant protein-1 (SMD, -0.11; 95% CI, -0.41 to 0.20; p = 0.49; I2 = 0%) when compared with placebo. No obvious publication bias was observed (p>0.05). In conclusion, the present meta-analysis of available randomized controlled studies did not suggest any significant benefit of microbiota-driven therapy in decreasing the inflammatory responses of elderly individuals.

]]>
<![CDATA[Efficacy assessment of commercially available natural products and antibiotics, commonly used for mitigation of pathogenic Vibrio outbreaks in Ecuadorian Penaeus (Litopenaeus) vannamei hatcheries]]> https://www.researchpad.co/article/5c5b52ebd5eed0c4842bd266

Bacterial diseases cause high mortality in Penaeus (Litopenaeus) vannamei postlarvae. Therefore, appropriate application of efficient therapeutic products is of vital importance for disease control. This study evaluated through in vitro analyses the antimicrobial effectiveness of commercial therapeutic products used for P. vannamei bacterial diseases and antibiotics against pathogenic Vibrio strains circulating in Ecuadorian hatcheries. Twenty strains were isolated from 31 larvae samples with high bacterial counts from 10 hatcheries collected during mortality events. The strains virulence was verified through challenge tests with Artemia franciscana nauplii and P. vannamei postlarvae. Through 16S rRNA sequence analysis, strains showed a great similarity to the Vibrio sequences reported as pathogens, with 95% belonging to the Harveyi clade. Through antibiograms and minimal inhibitory concentration (MIC) in vitro tests we found that furazolidone, ciprofloxacin, chloramphenicol, norfloxacin, nalidixic acid, florfenicol, fosfomycin and enrofloxacin inhibited the growth of all or most of the strains. Less efficient antibiotics were penicillin, oxytetracycline and tetracycline. A multiple antibiotic resistance (MAR) index of 0.23 showed some level of resistance to antibiotics, with two MAR prevalent patterns (Penicillin-Oxytetracycline and Penicillin-Oxytetracycline-Tetracycline). From a total of 16 natural products (five probiotics, nine organic acids and two essential oils), only three (one probiotic, one organic acid and one essential oil) were effective to control most of the strains. Shrimp producers can apply relatively simple in vitro analyses, such as those employed in this study, to help take adequate management decisions to reduce the impact of bacterial diseases and increase profit.

]]>
<![CDATA[Use of Lactobacillus crispatus to produce a probiotic cheese as potential gender food for preventing gynaecological infections]]> https://www.researchpad.co/article/5c3fa5c7d5eed0c484ca86ed

This research is aimed to evaluate the suitability of Squacquerone cheese to support the viability of Lactobacillus crispatus BC4, a vaginal strain endowed with a strong antimicrobial activity against urogenital pathogens and foodborne microorganisms, in order to recommend a gender food for woman wellbeing. The viability of L. crispatus BC4, used as adjunct culture, was evaluated during the refrigerated storage of Squacquerone cheese, as well as when the cheese was subjected to simulated stomach-duodenum passage tested by the patented Simulator of the Human Intestinal Microbial Ecosystem (SHIME). Moreover, the effects of L. crispatus BC4 addition were evaluated on product hydrolytic patterns, in terms of proteolysis, lipolysis and volatile molecule profiles. The data showed that L. crispatus BC4 maintained high viability, also in presence of physiological stress conditions, until the end of the refrigerated storage. Moreover, the inclusion of L. crispatus BC4 gave rise to cheese product with higher score of overall acceptability when compared to control cheese. In addition, the survival of L. crispatus BC4, carried in test cheese, in gastro intestinal conditions was confirmed by SHIME. The results showed that the vaginal Lactobacillus strain was more affected by the low pH of the stomach, simulated by the SHIME reactor, rather than to bile salts and pancreatic juices. Although only in vivo trials will be able to confirm the functionality of the cheese in the vaginal environment, these data represent a first step towards the employment of the Squacquerone cheese as probiotic food able to promote the woman’s health by preventing gynaecological infections.

]]>
<![CDATA[Pilot study of probiotic/colostrum supplementation on gut function in children with autism and gastrointestinal symptoms]]> https://www.researchpad.co/article/5c3fa56ed5eed0c484ca43d3

Over half of all children with autism spectrum disorders (ASD) have gastrointestinal (GI) co-morbidities including chronic constipation, diarrhea, and irritable bowel syndrome. The severity of these symptoms has been correlated with the degree of GI microbial dysbiosis. The study objective was to assess tolerability of a probiotic (Bifidobacterium infantis) in combination with a bovine colostrum product (BCP) as a source of prebiotic oligosaccharides and to evaluate GI, microbiome and immune factors in children with ASD and GI co-morbidities. This pilot study is a randomized, double blind, controlled trial of combination treatment (BCP + B. infantis) vs. BCP alone in a cross-over study in children ages 2–11 with ASD and GI co-morbidities (n = 8). This 12-week study included 5 weeks of probiotic-prebiotic supplementation, followed by a two-week washout period, and 5 weeks of prebiotic only supplementation. The primary outcome of tolerability was assessed using validated questionnaires of GI function and atypical behaviors, along with side effects. Results suggest that the combination treatment is well-tolerated in this cohort. The most common side effect was mild gassiness. Some participants on both treatments saw a reduction in the frequency of certain GI symptoms, as well as reduced occurrence of particular aberrant behaviors. Improvement may be explained by a reduction in IL-13 and TNF-α production in some participants. Although limited conclusions can be drawn from this small pilot study, the results support the need for further research into the efficacy of these treatments.

]]>
<![CDATA[Lack of mutagenicity, genotoxicity and developmental toxicity in safety assessment tests of Lactobacillus mali APS1]]> https://www.researchpad.co/article/5c1c0aeed5eed0c484426f00

Lactobacillus (L.) mali APS1 isolated from sugary kefir grains has been proven to affect energy and glucose homeostasis. However, without proper safety assessment it cannot be recommended as probiotics for human consumption. For genotoxicity, the Ames test showed no mutagenic effect of L. mali APS1 in the presence or absence of S9 mix metabolic activation. In-vitro mammalian chromosomal aberration test showed that the number of Chinese hamster ovary cells with abnormal chromosomes was <5% after L. mali APS1 treatment. Moreover, L. mali APS1 showed no risk of genotoxicity potential compared to the control. L. mali APS1 administration did not cause significant (p>0.05) changes in body weight, the number of reticulocytes, or in the occurrence percentage of micronucleus in Imprinting Control Region (ICR) mice. Based on the absence of maternal or fetal effects at any dosage level investigated, the teratogenicity could be defined as greater than 1,670 mg/kg b.w./day for maternal general toxicity and fetal development when L. mali APS1 was orally administered by gavage to pregnant SD rats during gestation days 6 to 15.

]]>
<![CDATA[Comparative genomics of transport proteins in seven Bacteroides species]]> https://www.researchpad.co/article/5c117bccd5eed0c48469a775

The communities of beneficial bacteria that live in our intestines, the gut microbiome, are important for the development and function of the immune system. Bacteroides species make up a significant fraction of the human gut microbiome, and can be probiotic and pathogenic, depending upon various genetic and environmental factors. These can cause disease conditions such as intra-abdominal sepsis, appendicitis, bacteremia, endocarditis, pericarditis, skin infections, brain abscesses and meningitis. In this study, we identify the transport systems and predict their substrates within seven Bacteroides species, all shown to be probiotic; however, four of them (B. thetaiotaomicron, B. vulgatus, B. ovatus, B. fragilis) can be pathogenic (probiotic and pathogenic; PAP), while B. cellulosilyticus, B. salanitronis and B. dorei are believed to play only probiotic roles (only probiotic; OP). The transport system characteristics of the four PAP and three OP strains were identified and tabulated, and results were compared among the seven strains, and with E. coli and Salmonella strains. The Bacteroides strains studied contain similarities and differences in the numbers and types of transport proteins tabulated, but both OP and PAP strains contain similar outer membrane carbohydrate receptors, pore-forming toxins and protein secretion systems, the similarities were noteworthy, but these Bacteroides strains showed striking differences with probiotic and pathogenic enteric bacteria, particularly with respect to their high affinity outer membrane receptors and auxiliary proteins involved in complex carbohydrate utilization. The results reveal striking similarities between the PAP and OP species of Bacteroides, and suggest that OP species may possess currently unrecognized pathogenic potential.

]]>
<![CDATA[Comparative effectiveness and safety of interventions for acute diarrhea and gastroenteritis in children: A systematic review and network meta-analysis]]> https://www.researchpad.co/article/5c117b2dd5eed0c48469825e

Background

Many interventions have shown effectiveness in reducing the duration of acute diarrhea and gastroenteritis (ADG) in children. Yet, there is lack of comparative efficacy of interventions that seem to be better than placebo among which, the clinicians must choose. Our aim was to determine the comparative effectiveness and safety of the pharmacological and nutritional interventions for reducing the duration of ADG in children.

Methods

Data sources included Medline, Embase, CENTRAL, CINAHL, LILACS, and Global-Health up to May 2017. Eligible trials compared zinc (ZN), vitamin A, micronutrients (MN), probiotics, prebiotics, symbiotics, racecadotril, smectite(SM), loperamide, diluted milk, lactose-free formula(LCF), or their combinations, to placebo or standard treatment (STND), or among them. Two reviewers independently performed screening, review, study selection and extraction. The primary outcome was diarrhea duration. Secondary outcomes were stool frequency at day 2, diarrhea at day 3, vomiting and side effects. We performed a random effects Bayesian network meta-analysis to combine the direct and indirect evidence for each outcome. Mean differences and odds ratio with their credible intervals(CrI) were calculated. Coherence and transitivity assumptions were assessed. Meta-regression, subgroups and sensitivity analyses were conducted to explore the impact of effect modifiers. Summary under the cumulative curve (SUCRA) values with their CrI were calculated. We assessed the evidence quality and classified the best interventions using the Grading of Recommendations, Assessment, Development & Evaluation (GRADE) approach for each paired comparison.

Results

A total of 174 studies (32,430 children) proved eligible. Studies were conducted in 42 countries of which most were low-and middle-income countries (LMIC). Interventions were grouped in 27 categories. Most interventions were better than STND. Reduction of diarrhea varied from 12.5 to 51.1 hours. The combinations Saccharomyces boulardii (SB)+ZN, and SM+ZN were considered the best interventions (i.e., GRADE quality of evidence: moderate to high, substantial superiority to STND, reduction in duration of 35 to 40 hours, and large SUCRA values), while symbiotics (combination of probiotics+prebiotics), ZN, loperamide and combinations ZN+MN and ZN+LCF were considered inferior to the best and better than STND [Quality: moderate to high, superior to STND, and reduction of 17 to 25 hours]. In subgroups analyses, effect of ZN was higher in LMIC and was not present in high-income countries (HIC). Vitamin A, MN, prebiotics, kaolin-pectin, and diluted milk were similar to STND [Quality: moderate to high]. The remainder of the interventions had low to very-low evidence quality. Loperamide was the only intervention with more side effects than STND [Quality: moderate].

Discussion/Conclusion

Most interventions analyzed (except vitamin A, micronutrients, prebiotics, and kaolin-pectin) showed evidence of superiority to placebo in reducing the diarrhea. With moderate-to high-quality of evidence, SB+ZN and SM+ZN, demonstrated the best combination of evidence quality and magnitude of effect while symbiotics, loperamide and zinc proved being the best single interventions, and loperamide was the most unsafe. Nonetheless, the effect of zinc, SB+ZN and SM+ZN might only be applied to children in LMIC. Results suggest no further role for studies comparing interventions against no treatment or placebo, or studies testing loperamide, MN, kaolin-pectin, vitamin A, prebiotics and diluted milk.

PROSPERO registration

CRD42015023778.

]]>
<![CDATA[Dopamine production in Enterococcus faecium: A microbial endocrinology-based mechanism for the selection of probiotics based on neurochemical-producing potential]]> https://www.researchpad.co/article/5c0841a9d5eed0c484fca615

The mechanisms by which probiotics may influence host physiology are still incompletely understood. Microbial endocrinology, a field representing the union of microbiology, endocrinology and neurobiology, has theorized that microorganisms have the capacity to serve as neurochemical delivery vehicles [1]. According to microbial endocrinology, neurochemicals can serve as a common language between host and bacterium, enabling bidirectional communication. We report herein the first demonstration that Enterococcus sp. has the capacity to produce dopamine in a gastrointestinal-like environment when supplied with the dopamine precursor L-3,4 dihydroxyphenylalanine (L-dopa). The results presented herein provide a means to select probiotics based on neurochemical-producing potential and suggest the possibility that probiotics containing E. faecium may serve to influence the host through dopaminergic pathways.

]]>
<![CDATA[Impact of Bacillus spp. spores and gentamicin on the gastrointestinal microbiota of suckling and newly weaned piglets]]> https://www.researchpad.co/article/5c06f027d5eed0c484c6d20c

Administrating antibiotics to young piglets may have short- and long-term consequences on the gut microbiota. We hypothesised that these consequences may be alleviated by concurrent probiotic administration. The study objective was to investigate the effect of administrating gentamicin and a mixture of Bacillus (B.) licheniformis, B. subtilis and B. amyloliquefaeceans spores on the gut microbiota of piglets pre- and post-weaning. Twenty-four sows and their litters were randomly allocated to four treatment groups receiving; a) Bacillus spore mixture (six B. subtilis, two B. amyloliquefaeceans, and one B. licheniformis) fed to sows and piglets (PRO); b) gentamicin (5 mg per day) administered to piglets on day 4, 5, and 6 of age (AB); c) Bacillus spore mixture fed to sows and piglets, and gentamicin to piglets (PRO+AB); or d) no administration of probiotics or antibiotics (CTRL). Faecal and digesta samples were collected repeatedly during the study. Selected samples were subjected to 16S rRNA gene sequencing, culture counts, and organic acid, biogenic amine and tissue gene expression analysis. Treatment had a significant effect on the faecal microbial community composition on day 28 and 42, and colonic community on day 28. Faecal species richness (observed and estimated) and Shannon index, and colonic species richness, were higher in AB compared to PRO piglets on day 28, and were not significantly different from day 42. PRO piglets had the highest faecal concentration of iso-butyric acid on day 7 and a higher butyric acid concentration compared to CTRL piglets. We conclude that gentamicin and Bacillus spores influence the gut microbial diversity of piglets, although administration of gentamicin did not result in dysbiosis as hypothesised.

]]>
<![CDATA[Pilot assessment of probiotics for pregnant women in Rwanda]]> https://www.researchpad.co/article/5b498fc4463d7e0897c6e026

Background

While the global market for probiotics is soon to reach in excess of US$50 billion, the continent of Africa has been largely ignored, despite these products having the ability to reduce the burden of disease and death.

Trial design

The present randomised, blinded, placebo-controlled clinical trial was undertaken in Rwanda, a country devoid of well-documented probiotics. The primary outcome aim was to examine receptivity and compliance for orally administered probiotic capsules containing Lactobacillus rhamnosus GR-1 and Lactobacillus reuteri RC-14 in pregnant women and assess any initial side effects or changes to the vaginal microbiome.

Methods

Pregnant women between the ages of 18 and 55 were recruited from the Nyamata District Hospital in Rwanda and randomly assigned to receive probiotic or placebo capsules for one month. Clinicians were blinded to the treatments.

Results

The drop-out rate was 21%, with 13 of 18 women in the placebo group and 17 of 20 in the probiotic group completing the study. Only 13 women returned for birthing and additional sample collection. No side effects of either treatment group were reported. Microbiota and metabolomics data showed similar findings to those reported in the literature, with low bacterial diversity and Lactobacillus dominance associated with a healthy vagina, and birthing associated with high diversity. Despite the small sample size and lack of changes in the microbiota, women in the placebo arm were significantly more likely to give birth pre-term.

Conclusion

Overall women were receptive to the probiotic concept, but the lack of information on such products and logistical and economical challenges pose problems for wider population engagement.

Trial registration

ClinicalTrials.gov NCT02150655

]]>
<![CDATA[Effects of Supplementation of the Synbiotic Ecologic® 825/FOS P6 on Intestinal Barrier Function in Healthy Humans: A Randomized Controlled Trial]]> https://www.researchpad.co/article/5989d9dbab0ee8fa60b6774e

Background and Aims

Probiotics, prebiotics and synbiotics have been suggested as dietary strategies to improve intestinal barrier function. This study aimed to assess the effect of two weeks synbiotic supplementation on intestinal permeability under basal and stressed conditions. Secondary aims were the assessment of two weeks synbiotic supplementation on systemic immune function and gastrointestinal symptoms including defecation pattern.

Design

Twenty healthy adults completed a double-blind, controlled, randomized, parallel design study.

Intervention

Groups either received synbiotic (1.5 × 1010 CFU Ecologic® 825 + 10 g fructo-oligosaccharides (FOS P6) per day) or control supplements for two weeks.

Outcomes

Intestinal segment specific permeability was assessed non-invasively by oral administration of multiple sugar probes and, subsequently, assessing the excretion of these probes in urine. This test was conducted at baseline and at the end of intervention, in the absence and in the presence of an indomethacin challenge. Indomethacin was applied to induce a compromised gut state. Plasma zonulin, cytokines and chemokines were measured at baseline and at the end of intervention. Gastrointestinal symptoms and stool frequency were recorded at baseline and daily during intervention.

Results

Significantly more male subjects were in the synbiotic group compared to the control group (P = 0.025). Indomethacin significantly increased urinary lactulose/rhamnose ratio versus without indomethacin, both in the control group (P = 0.005) and in the synbiotic group (P = 0.017). Urinary sugar recoveries and ratios, plasma levels of zonulin, cytokines and chemokines, and gastrointestinal symptom scores were not significantly different after control or synbiotic intervention. Stool frequency within the synbiotic group was significantly increased during synbiotic intervention compared to baseline (P = 0.039) and higher compared to control intervention (P = 0.045).

Conclusion

Two weeks Ecologic® 825/FOS P6 supplementation increased stool frequency, but did not affect intestinal permeability neither under basal nor under indomethacin-induced stressed conditions, immune function or gastrointestinal symptoms in healthy adults.

]]>
<![CDATA[Genome-Wide Immune Modulation of TLR3-Mediated Inflammation in Intestinal Epithelial Cells Differs between Single and Multi-Strain Probiotic Combination]]> https://www.researchpad.co/article/5989d9e4ab0ee8fa60b6ac07

Genome-wide transcriptional analysis in intestinal epithelial cells (IEC) can aid in elucidating the impact of single versus multi-strain probiotic combinations on immunological and cellular mechanisms of action. In this study we used human expression microarray chips in an in vitro intestinal epithelial cell model to investigate the impact of three probiotic bacteria, Lactobacillus helveticus R0052 (Lh-R0052), Bifidobacterium longum subsp. infantis R0033 (Bl-R0033) and Bifidobacterium bifidum R0071 (Bb-R0071) individually and in combination, and of a surface-layer protein (SLP) purified from Lh-R0052, on HT-29 cells’ transcriptional profile to poly(I:C)-induced inflammation. Hierarchical heat map clustering, Set Distiller and String analyses revealed that the effects of Lh-R0052 and Bb-R0071 diverged from those of Bl-R0033 and Lh-R0052-SLP. It was evident from the global analyses with respect to the immune, cellular and homeostasis related pathways that the co-challenge with probiotic combination (PC) vastly differed in its effect from the single strains and Lh-R0052-SLP treatments. The multi-strain PC resulted in a greater reduction of modulated genes, found through functional connections between immune and cellular pathways. Cytokine and chemokine analyses based on specific outcomes from the TNF-α and NF-κB signaling pathways revealed single, multi-strain and Lh-R0052-SLP specific attenuation of the majority of proteins measured (TNF-α, IL-8, CXCL1, CXCL2 and CXCL10), indicating potentially different mechanisms. These findings indicate a synergistic effect of the bacterial combinations relative to the single strain and Lh-R0052-SLP treatments in resolving toll-like receptor 3 (TLR3)-induced inflammation in IEC and maintaining cellular homeostasis, reinforcing the rationale for using multi-strain formulations as a probiotic.

]]>
<![CDATA[Health claims on foods: challenge for clinical research companies]]> https://www.researchpad.co/article/5acd5cdf463d7e1654cd9f27

Background

The Nutrition and Health Claim Regulation 1924/2006/EC, together with EFSA guidances on the scientific requirements for different type of health claims, is setting the basis for health claim substantiation in the EU.

Aim

The aim of this presentation is to bring up the key challenges that the food industry and clinical research organizations are facing when meeting these requirements.

Results and discussion

Key issues in clinical research planning to meet the requirements set for the health claim substantiation are: (1) Selection of right outcome markers since the selection of outcome marker defines actually the formulation of the health claim to be used on food or food ingredient. (2) Selection of right target population since that determines the target consumer group for the food with a health claim. (3) Selection of dose regime and food matrices used since these largely determine the conditions set for the use of the health claim. One of the major challenges in health claim substantiation is the deviant approach to risk factors or biomarkers. From the regulation point of view, a single risk factor approach is emphasized, but from the clinical and scientific point of view the pattern of different risk markers or biomarkers could, in some cases, be a more relevant choice to reflect the final health outcome. This is especially the case in the nutrition and health area because we are often dealing with weak but multiple health effects of certain food items or ingredients. Also the lack of validated well-established biomarkers potent to be affected by diet is a challenge in health claim substantiation.

The selection of right target population is often a compromise between choosing a more potential target group to obtain efficacy (i.e. risk factors elevated vs. patient groups) and choosing a rationale to generalize the results to wider population (target consumer) group.

The selection of optimal dosing regime and matrices for a clinical study is partly dependent on previous scientific data on the dose response, if existing. But equally important is the choice of feasible doses from product formulation and food consumption point of view.

Conclusion

With careful analysis of the existing data, advance planning and clinical research strategy it is possible to build up a health claim substantiation that meets the requirements both of Nutrition and Health Claim Regulation and EFSA.

]]>
<![CDATA[Benefits of Bifidobacterium breve M-16V Supplementation in Preterm Neonates - A Retrospective Cohort Study]]> https://www.researchpad.co/article/5989da52ab0ee8fa60b8e297

Background

Systematic reviews of randomised controlled trials report that probiotics reduce the risk of necrotising enterocolitis (NEC) in preterm neonates.

Aim

To determine whether routine probiotic supplementation (RPS) to preterm neonates would reduce the incidence of NEC.

Methods

The incidence of NEC ≥ Stage II and all-cause mortality was compared for an equal period of 24 months ‘before’ (Epoch 1) and ‘after’ (Epoch 2) RPS with Bifidobacterium breve M-16V in neonates <34 weeks. Multivariate logistic regression analysis was conducted to adjust for relevant confounders.

Results

A total of 1755 neonates (Epoch I vs. II: 835 vs. 920) with comparable gestation and birth weights were admitted. There was a significant reduction in NEC ≥ Stage II: 3% vs. 1%, adjusted odds ratio (aOR) = 0.43 (95%CI: 0.21–0.87); ‘NEC ≥ Stage II or all-cause mortality’: 9% vs. 5%, aOR = 0.53 (95%CI: 0.32–0.88); but not all-cause mortality alone: 7% vs. 4%, aOR = 0.58 (95% CI: 0.31–1.06) in Epoch II. The benefits in neonates <28 weeks did not reach statistical significance: NEC ≥ Stage II: 6% vs. 3%, aOR 0.51 (95%CI: 0.20–1.27), ‘NEC ≥ Stage II or all-cause mortality’, 21% vs. 14%, aOR = 0.59 (95%CI: 0.29–1.18); all-cause mortality: 17% vs. 11%, aOR = 0.63 (95%CI: 0.28–1.41). There was no probiotic sepsis.

Conclusion

RPS with Bifidobacterium breve M-16V was associated with decreased NEC≥ Stage II and ‘NEC≥ Stage II or all-cause mortality’ in neonates <34 weeks. Large sample size is required to assess the potential benefits of RPS in neonates <28 weeks.

]]>
<![CDATA[Investigating the Effect of Different Treatments with Lactic Acid Bacteria on the Fate of Listeria monocytogenes and Staphylococcus aureus Infection in Galleria mellonella Larvae]]> https://www.researchpad.co/article/5989daa5ab0ee8fa60ba71d4

The use of Galleria mellonella as a model host to elucidate microbial pathogenesis and search for novel drugs and therapies has been well appreciated over the past years. However, the effect of microorganisms with functional appeal in the specific host remains scarce. The present study investigates the effect of treatment with selected lactic acid bacteria (LAB) with probiotic potential, as potential protective agents by using live or heat-killed cells at 6 and 24 h prior to infection with Listeria monocytogenes and Staphylococcus aureus or as potential therapeutic agents by using cell-free supernatants (CFS) after infection with the same pathogens. The employed LAB strains were Lactobacillus pentosus B281 and Lactobacillus plantarum B282 (isolated from table olive fermentations) along with Lactobacillus rhamnosus GG (inhabitant of human intestinal tract). Kaplan-Meier survival curves were plotted while the pathogen’s persistence in the larval hemolymph was determined by microbiological analysis. It was observed that the time (6 or 24 h) and type (live or heat-killed cells) of challenge period with LAB prior to infection greatly affected the survival of infected larvae. The highest decrease of L. monocytogenes population in the hemolymph was observed in groups challenged for 6 h with heat-killed cells by an average of 1.8 log units compared to non challenged larvae for strains B281 (p 0.0322), B282 (p 0.0325), and LGG (p 0.0356). In the case of S. aureus infection, the population of the pathogen decreased in the hemolymph by 1 log units at 8 h post infection in the groups challenged for 6 h with heat-killed cells of strains B281 (p 0.0161) and B282 (p 0.0096) and by 1.8 log units in groups challenged with heat-killed cells of LGG strain (p 0.0175). Further use of CFS of each LAB strain did not result in any significant prolonged survival but interestingly it resulted in pronounced decrease of L. monocytogenes in the hemolymph at 24 h and 48 h after infection by more than 1 log unit (p < 0.05) depending on the strain. The results of the present work support the broader use of G. mellonella larvae as a low cost in vivo tool for screening for probiotic properties.

]]>
<![CDATA[A Systems Biology Approach Investigating the Effect of Probiotics on the Vaginal Microbiome and Host Responses in a Double Blind, Placebo-Controlled Clinical Trial of Post-Menopausal Women]]> https://www.researchpad.co/article/5989daf1ab0ee8fa60bc138d

A lactobacilli dominated microbiota in most pre and post-menopausal women is an indicator of vaginal health. The objective of this double blinded, placebo-controlled crossover study was to evaluate in 14 post-menopausal women with an intermediate Nugent score, the effect of 3 days of vaginal administration of probiotic L. rhamnosus GR-1 and L. reuteri RC-14 (2.5×109 CFU each) on the microbiota and host response. The probiotic treatment did not result in an improved Nugent score when compared to when placebo. Analysis using 16S rRNA sequencing and metabolomics profiling revealed that the relative abundance of Lactobacillus was increased following probiotic administration as compared to placebo, which was weakly associated with an increase in lactate levels. A decrease in Atopobium was also observed. Analysis of host responses by microarray showed the probiotics had an immune-modulatory response including effects on pattern recognition receptors such as TLR2 while also affecting epithelial barrier function. This is the first study to use an interactomic approach for the study of vaginal probiotic administration in post-menopausal women. It shows that in some cases multifaceted approaches are required to detect the subtle molecular changes induced by the host to instillation of probiotic strains.

Trial Registration

ClinicalTrials.gov NCT02139839

]]>