Probiotic Lactobacillus Rhamnosus HN001 Research Articles

A randomized trial of probiotic supplementation in nurses to reduce stress and viral illness

Animal studies demonstrate how the gut microbiota influence psychological health and immunity to viral infections through their actions along multiple dynamic pathways in the body. Considerable interest exists in probiotics to reduce stress and illness symptoms through beneficial effects in the gut, but translating pre-clinical evidence from animal models into humans remains challenging. We conducted a large trial in nurses working during the 2020 COVID19 pandemic year to establish whether daily ingestion of the probiotic Lactobacillus rhamnosus HN001 reduced perceived stress and the number of days participants reported symptoms of a viral illness. Our results showed no significant difference in perceived stress or the average number of illness days between probiotic supplemented nurses and the placebo group. Stress and viral illness symptoms reduced during the study for all participants, a trajectory likely influenced by societal-level factors. The powerful effect of a well-managed public health response to the COVID19 pandemic and the elimination of COVID19 from the community in 2020 may have altered the trajectory of stress levels and reduced circulating viral infections making it difficult to detect any effect of probiotic supplementation. Our study highlights the challenge in controlling environmental factors in human trials.

A randomised controlled trial of a probiotic and a prebiotic examining metabolic and mental health outcomes in adults with pre-diabetes

AimsTo evaluate the effect of the probiotic Lactobacillus rhamnosus HN001 and/or cereal enriched with oat-derived beta-glucan (OBG) on metabolic and mental health outcomes when administered to adults with pre-diabetes.Design2×2 factorial...

Potential probiotic salami with dietary fiber modulates metabolism and gut microbiota in a human intervention study

A human intervention in 24 healthy volunteers was performed to test the potential health benefits of a fermented salami with a probiotic Lactobacillus rhamnosus HN001 and added citrus fiber. Anthropometric measurements and blood biochemistry did not show any significant differences between pre- and post-intervention during 4 weeks with a daily intake of 30 g of salami, neither with regular salami (control group) nor with reformulated salami (intervention group). However, the inflammatory markers CRP and TNFα decreased significantly after intervention, suggesting a less inflammatory environment after reformulated salami consumption. Antioxidant plasmatic markers also improved within the intervention group. Butyrate production was significantly increased after reformulated salami consumption. Gut microbiota community structure, however, was not significantly shaped by neither regular nor reformulated salami. After the intervention with probiotic salami, L. rhamnosus was detected by quantitative polymerase chain reaction (qPCR) in all samples of the intervention group but not in the control group, showing probiotic effect.

Eczema-protective probiotic alters infant gut microbiome functional capacity but not composition: sub-sample analysis from a RCT.

Probiotic Lactobacillus rhamnosus HN001 given in early life has been shown to reduce infant eczema risk, but its effect on gut microbiota development has not been quantitatively and functionally examined. The aim of this study was to investigate the impact of early life probiotic exposure on the composition and functional capacity of infant gut microbiota from birth to 2 years considering the effects of age, delivery mode, antibiotics, pets and eczema. We performed shotgun metagenomic sequencing analysis of 650 infant faecal samples, collected at birth, 3, 12, and 24 months, as part of a randomised, controlled, 3-arm trial assessing the effect of L. rhamnosus HN001, Bifidobacterium animalis subsp. lactis HN019 supplementation on eczema development in 474 infants. There was a 50% reduced eczema risk in the HN001 probiotic group compared to placebo. Both mothers (from 35 weeks gestation until 6 months post-partum if breastfeeding) and infants (from birth to 2 years) received either a placebo or one of two probiotics, L. rhamnosus HN001 (6×109 cfu), or B. animalis subsp. lactis HN019 (9×109 cfu). L. rhamnosus HN001 probiotic supplementation was associated with increased overall glycerol-3 phosphate transport capacity and enrichment of L. rhamnosus. There were no other significant changes in infant gut microbiota composition or diversity. Increased capacity to transport glycerol-3-phosphate was positively correlated with relative abundance of L. rhamnosus. Children who developed eczema had gut microbiota with increased capacity for glycosaminoglycan degradation and flagellum assembly but had no significant differences in microbiota composition or diversity. Early life HN001 probiotic use is associated with both increased L. rhamnosus and increased infant gut microbiota functional capacity to transport glycerol-3 phosphate. The mechanistic relationship of such functional alteration in gut microbiota with reduced eczema risk and long-term health merits further investigation.

Maternal supplementation alone with Lactobacillus rhamnosus HN001 during pregnancy and breastfeeding does not reduce infant eczema.

In a randomized placebo-controlled trial, we previously found that the probiotic Lactobacillus rhamnosus HN001 (HN001) taken by mothers from 35weeks of gestation until 6months post-partum if breastfeeding and their child from birth to age 2years halved the risk of eczema during the first 2years of life. We aimed to test whether maternal supplementation alone is sufficient to reduce eczema and compare this to our previous study when both the mother and their child were supplemented. In this 2-centre, parallel double-blind, randomized placebo-controlled trial, the same probiotic as in our previous study (HN001, 6×109 colony-forming units) was taken daily by mothers from 14-16weeks of gestation till 6months post-partum if breastfeeding, but was not given directly to the child. Women were recruited from the same study population as the first study, where they or their partner had a history of treated asthma, eczema or hay fever. Women were randomized to HN001 (N=212) or placebo (N=211). Maternal-only HN001 supplementation did not significantly reduce the prevalence of eczema, SCORAD≥10, wheeze or atopic sensitization in the infant by 12months. This contrasts with the mother and child intervention study, where HN001 was associated with reductions in eczema (hazard ratio (HR): 0.39, 95% CI 0.19-0.79, P=.009) and SCORAD (HR=0.61, 95% 0.37-1.02). However, differences in the HN001 effect between studies were not significant. HN001 could not be detected in breastmilk from supplemented mothers, and breastmilk TGF-β/IgA profiles were unchanged. Maternal probiotic supplementation without infant supplementation may not be effective for preventing infant eczema.

Early pregnancy probiotic supplementation with Lactobacillus rhamnosus HN001 may reduce the prevalence of gestational diabetes mellitus: a randomised controlled trial.

The study aims to assess whether supplementation with the probiotic Lactobacillus rhamnosus HN001 (HN001) can reduce the prevalence of gestational diabetes mellitus (GDM). A double-blind, randomised, placebo-controlled parallel trial was conducted in New Zealand (NZ) (Wellington and Auckland). Pregnant women with a personal or partner history of atopic disease were randomised at 14-16 weeks' gestation to receive HN001 (6×109 colony-forming units) (n 212) or placebo (n 211) daily. GDM at 24-30 weeks was assessed using the definition of the International Association of Diabetes and Pregnancy Study Groups (IADPSG) (fasting plasma glucose ≥5·1 mmol/l, or 1 h post 75 g glucose level at ≥10 mmol/l or at 2 h ≥8·5 mmol/l) and NZ definition (fasting plasma glucose ≥5·5 mmol/l or 2 h post 75 g glucose at ≥9 mmol/l). All analyses were intention-to-treat. A total of 184 (87 %) women took HN001 and 189 (90 %) women took placebo. There was a trend towards lower relative rates (RR) of GDM (IADPSG definition) in the HN001 group, 0·59 (95 % CI 0·32, 1·08) (P=0·08). HN001 was associated with lower rates of GDM in women aged ≥35 years (RR 0·31; 95 % CI 0·12, 0·81, P=0·009) and women with a history of GDM (RR 0·00; 95 % CI 0·00, 0·66, P=0·004). These rates did not differ significantly from those of women without these characteristics. Using the NZ definition, GDM prevalence was significantly lower in the HN001 group, 2·1 % (95 % CI 0·6, 5·2), v. 6·5 % (95 % CI 3·5, 10·9) in the placebo group (P=0·03). HN001 supplementation from 14 to 16 weeks' gestation may reduce GDM prevalence, particularly among older women and those with previous GDM.

The Probiotics in Pregnancy Study (PiP Study): rationale and design of a double-blind randomised controlled trial to improve maternal health during pregnancy and prevent infant eczema and allergy.

BackgroundWorldwide there is increasing interest in the manipulation of human gut microbiota by the use of probiotic supplements to modify or prevent a range of communicable and non-communicable diseases. Probiotic interventions administered during pregnancy and breastfeeding offer a unique opportunity to influence a range of important maternal and infant outcomes.The aim of the Probiotics in Pregnancy Study (PiP Study) is to assess if supplementation by the probiotic Lactobacillus rhamnosus HN001 administered to women from early pregnancy and while breastfeeding can reduce the rates of infant eczema and atopic sensitisation at 1 year, and maternal gestational diabetes mellitus, bacterial vaginosis and Group B Streptococcal vaginal colonisation before birth, and depression and anxiety postpartum.Methods/designThe PiP Study is a two-centre, randomised, double-blind placebo-controlled trial in Wellington and Auckland, New Zealand. Four hundred pregnant women expecting infants at high risk of allergic disease will be enrolled in the study at 14–16 weeks gestation and randomised to receive either Lactobacillus rhamnosus HN001 (6 × 109 colony-forming units per day (cfu/day)) or placebo until delivery and then continuing until 6 months post-partum, if breastfeeding.Primary infant outcomes are the development and severity of eczema and atopic sensitisation in the first year of life. Secondary outcomes are diagnosis of maternal gestational diabetes mellitus, presence of bacterial vaginosis and vaginal carriage of Group B Streptococcus (at 35–37 weeks gestation). Other outcome measures include maternal weight gain, maternal postpartum depression and anxiety, infant birth weight, preterm birth, and rate of caesarean sections. A range of samples including maternal and infant faecal samples, maternal blood samples, cord blood and infant cord tissue samples, breast milk, infant skin swabs and infant buccal swabs will be collected for the investigation of the mechanisms of probiotic action.DiscussionThe study will investigate if mother-only supplementation with Lactobacillus rhamnosus HN001 in pregnancy and while breastfeeding can reduce rates of eczema and atopic sensitisation in infants by 1 year, and reduce maternal rates of gestational diabetes mellitus, bacterial vaginosis, vaginal carriage of Group B Streptococcus before birth and maternal depression and anxiety postpartum.Trial registrationAustralian New Zealand Clinical Trials Registration: ACTRN12612000196842.Date Registered: 15/02/12.Electronic supplementary materialThe online version of this article (doi:10.1186/s12884-016-0923-y) contains supplementary material, which is available to authorized users.

Effects of Lactobacillus rhamnosus HN001 on acute respiratory infections and intestinal secretory IgA in children.

Acute respiratory infections (ARI) are one of the main health problems in children, particularly in those under 5 years of age. The aim of this study was to evaluate whether the regular intake of the probiotic Lactobacillus rhamnosus HN001 affects the frequency, severity or duration of ARI in children attending day care centers during the winter season. A double-blind, placebo-controlled trial was carried out in 398 children (1 to 5 years old) who were randomized into two groups to receive daily for 3 months either 100 mL of a product containing HN001 (1010 bacteria/day) or a control without the probiotic. ARI episodes and symptoms, absenteeism and antibiotic administration were registered. In a sub-group of children, oropharyngeal and fecal samples were obtained to detect pathogens, total Lactobacillus counts and secretory IgA, respectively. When comparing groups, neither the number nor the duration of the ARI, nor the days of absenteeism or antibiotic administration were statistically different. No differences between the groups in the detection rates of Staphylococcus aureus, Streptococcus pneumoniae and Streptococcus pyogenes in the oropharyngeal samples were observed along the study. Fecal Lactobacillus counts as well as sIgA levels increased significantly during the study in the HN001 group, compared to the control (P = 0.027 and P = 0.048, respectively). In the conditions in which this study was carried out, the regular intake of L. rhamnosus HN001 modulated the intestinal immune responses without affecting the frequency or severity of ARI in children.

The effect of probiotic Lactobacillus rhamnosus HN001 on the in vitro availability of minerals from cheeses and cheese-like products

This study determined the effect of the Lactobacillus rhamnosus HN001 probiotic culture on the availability of calcium, magnesium, zinc, phosphorus and potassium. Due to variations in the rate of lactic acid fermentation, calcium concentrations were significantly higher in cheese-like products than in ripened cheeses. The contents of the remaining minerals were comparable in ripened cheeses and in cheese-like products. Enzymatic hydrolysis in vitro revealed that calcium was the least-available element (∼16%). The average availability of phosphorus, potassium, zinc and magnesium was significantly higher at ∼94%, 69%, 65% and 58%, respectively. The highest availability of Ca, Mg and Zn was observed in ripened cheese-like products and the lowest was in Swiss-type cheese. The highest availability of P and K was observed in ripened cheeses, but the difference was not significant. The addition of L. rhamnosus HN001 significantly increased the availability of calcium and magnesium from Dutch-type cheese and the availability of potassium and phosphorus from cheese-like products.

Viability of the Lactobacillus rhamnosus HN001 probiotic strain in Swiss- and Dutch-type cheese and cheese-like products.

The objective of this study was to determine the viability of the probiotic Lactobacillus rhamnosus HN001 in Swiss-type and Dutch-type cheese and cheese-like products (milk fat is substituted by stearin fraction of palm fat) during manufacture, ripening, and storage. The use of the probiotic L. rhamnosus HN001 in Dutch-type cheese and cheese-like products significantly (P = 0.1) changed their chemical composition (protein and fat content) and an insignificant increase (approximately 1.6% in cheese-like products and approximately 0.3% in cheese) in yield. L. rhamnosus HN001 did not affect the rate of changes in the pH of ripened cheese and cheese-like products. A minor increase in probiotic counts was observed in initial stages of production and were partially removed with whey. Ripened cheese and cheese-like products were characterized by high survival rates of probiotic bacteria which exceeded 8 log CFU/g after ripening. An insignificant reduction in the number of viable probiotic cells was noted during storage of Swiss-type and Dutch-type cheese, whereas a significant increase in probiotic cell counts was observed in cheese-like products during storage.

O09 ‐ Early supplementation with Lactobacillus rhamnosus HN001 reduces eczema prevalence to 6 years: does it also reduce atopic sensitisation?

Standard procedures were used to assess eczema (The UK Working Party’s criteria), eczema severity (SCORAD), atopic sensitization (skin prick tests (SPT), total and specific IgE) and standard questions used for asthma, wheeze and rhinoconjunctivitis. Results HN001 was associated with significantly lower cumulative prevalence of eczema (HR=0.56, 95% CI 0.39-0.80), SCORAD≥10 (HR=0.69, 0.49-0.98) and SPT sensitization (HR=0.69, 95% CI 0.48-0.99). The point prevalence of eczema (RR=0.66, 95% CI 0.44-1.00), SCORAD≥10 (RR=0.62, 95% CI 0.38-1.01) and SPT sensitization (RR=0.72, 95% CI 0.53-1.00) were also reduced among children taking HN001. HN019 had no significant effect on any outcome. Conclusion and clinical relevance This study provides evidence for the efficacy of the probiotic Lactobacillus rhamnosus HN001 in preventing the development of eczema and possibly also atopic sensitization in high risk infants to age 6 years. The absence of a similar effect for HN019 indicates that benefits may be species-specific.

Impact ofSaccharomyces Cerevisiaeon Viability of ProbioticLactobacillus Rhamnosusin Fermented Milk under Ambient Conditions

The viability of probiotic Lactobacillus rhamnosus HN001 was examined in fermented milk with and without Saccharomyces cerevisiae var. bayanus EC-1118. The yeast enhanced the viability of L. rhamnosus at 30C but not at 12C. High temperature (40C) was detrimental to yeast vitality and diminished its viability-enhancing effect. The yeast inoculated at 103 cfu/g multiplied to 106 cfu/g and enhanced the viability of L. rhamnosus. Viable yeast exerted maximum beneficial effects, although the cell-free yeast supernatant also enhanced the survival of L. rhamnosus. The addition of yeast after fermentation decreased its viability-enhancing effect. Removal of oxygen achieved the viability of L. rhamnosus that was comparable with that achieved in the presence of viable yeast. The results suggest that the improved viability of L. rhamnosus might involve yeast viability, oxygen removal and yeast metabolite(s). The findings would help develop novel microbial starter technology for ambient-stable fermented milks with live probiotics. Practical Applications Maintaining cell viability of probiotics is a scientific challenge, especially under ambient conditions. The findings of this study would lay the foundation for developing novel microbial starter technology for ambient-stable fermented foods with high cell counts of live probiotics, which entails stringent process and engineering control to ensure hygienic conditions and product safety. Benefits of such products would include: reducing distribution and storage costs by saving capital cost involved in chilled-chain distribution, storage and retailing; market penetration and growth where it was not possible due to a lack of or poor refrigeration; extending shelf life and increasing consumer convenience.

Immunostimulatory probiotic Lactobacillus rhamnosus HN001 and Bifidobacterium lactis HN019 do not induce pathological inflammation in mouse model of experimental autoimmune thyroiditis

The possibility that intestinal microflora contribute to the pathogenesis of autoimmune diseases has raised issues regarding the safety of probiotic organisms, especially those with immunostimulating properties, in individuals with such immune dysfunctions. In this study, the effect of consumption of probiotic lactic acid bacteria (LAB) strains Lactobacillus rhamnosus HN001(HN001) and Bifidobacterium lactis HN019 (HN019) on the induction and progression of experimental autoimmune thyroiditis (EAT) was investigated in CBA/CaH (H-2 k) mice. HN001 or HN019 in skim milk were fed to mice daily (1–1.5×10 8 cfu/mouse/day) for 5 to 9 weeks. A mild form of EAT was induced by subcutaneous injection of mouse thyroglobulin (MTg) with either Freund's adjuvant (complete and incomplete, CFA and IFA) or lipopolysaccharide (LPS). The proliferative responses of spleen lymphocyte to MTg stimulation in vitro and the presence (and degree) of mononuclear cell infiltration in thyroid gland tissues were examined to assess the development and severity of EAT. The levels of serum anti-MTg antibodies (IgG1 and IgG2a) and spleen weight index were determined to detect the presence of autoimmune responses of mice receiving MTg. Results showed that 8 weeks after immunization, 16.67–50% of the mice developed mild EAT with lymphocyte infiltration in the thyroid glands. Probiotic feeding did not induce full-blown EAT. There were no differences in spleen weight index or the proliferative spleenocytes in response to PMA between mice that received MTg alone and mice that received MTg and probiotic LAB strains.

Immune protection mediated by the probiotic Lactobacillus rhamnosus HN001 (DR20™) against Escherichia coli O157:H7 infection in mice

This study investigated the protective effects of feeding the immunoenhancing probiotic Lactobacillus rhamnosus HN001 against Escherichia coli O157:H7 infection in murine (BALB/c and C57BL/6 mice) challenge infection models. Mice were fed milk-based diets supplemented with L. rhamnosus HN001 (3×10 8 cfu g −1) for 7 days prior to and following oral challenge with E. coli O157:H7. Morbidity and feed intake were measured for 1 week following challenge; pathogen translocation to spleen, liver and blood, and humoral and cellular immunological responses (specific antibody and phagocytosis) were measured in a sub-sample of ostensibly healthy animals 1 week post-challenge. Results showed that, after challenge, L. rhamnosus HN001-fed mice exhibited lower cumulative morbidity and bacterial translocation rates, compared to non-probiotic-fed control mice. Significantly higher intestinal anti- E. coli IgA responses and blood leucocyte phagocytic activity were recorded among probiotic-fed mice compared to controls. These results demonstrate that feeding the probiotic L. rhamnosus HN001 to mice can reduce the severity of E. coli O157:H7 infection, and suggest that this reduction may be associated with enhanced humoral and cellular immune responses.

Immune protection mediated by the probiotic Lactobacillus rhamnosus HN001 (DR20) against Escherichia coli O157:H7 infection in mice.

This study investigated the protective effects of feeding the immunoenhancing probiotic Lactobacillus rhamnosus HN001 against Escherichia coli O157:H7 infection in murine (BALB/c and C57BL/6 mice) challenge infection models. Mice were fed milk-based diets supplemented with L. rhamnosus HN001 (3 x 10(8) cfu g(-1)) for 7 days prior to and following oral challenge with E. coli O157:H7. Morbidity and feed intake were measured for 1 week following challenge; pathogen translocation to spleen, liver and blood, and humoral and cellular immunological responses (specific antibody and phagocytosis) were measured in a sub-sample of ostensibly healthy animals 1 week post-challenge. Results showed that, after challenge, L. rhamnosus HN001-fed mice exhibited lower cumulative morbidity and bacterial translocation rates, compared to non-probiotic-fed control mice. Significantly higher intestinal anti-E. coli IgA responses and blood leucocyte phagocytic activity were recorded among probiotic-fed mice compared to controls. These results demonstrate that feeding the probiotic L. rhamnosus HN001 to mice can reduce the severity of E. coli O157:H7 infection, and suggest that this reduction may be associated with enhanced humoral and cellular immune responses.

Immune enhancement conferred by oral delivery of Lactobacillus rhamnosus HN001 in different milk-based substrates.

The probiotic Lactobacillus rhamnosus HN001 is known to enhance immunity in animal models, following oral delivery. In this study, we investigated the immunoenhancing effects of HN001 delivered to mice in different milk-based substrates, including: whole (full-fat) milk supplemented with HN001; fermented milk supplemented with HN001; or whole milk which had been part-fermented by HN001. Direct oral feeding of mice with HN001 in whole milk was shown to enhance the phagocytic activity of blood and peritoneal cells. Similar effects on phagocytosis were observed when UN001 was offered to mice in the form of a milk- or fermented milk-based diet. The degree of immune enhancement conferred by HN001 was similar whether the probiotic was used as an additive or as a fermentative agent. These studies confirm that Lb. rhamnosus HN001, derived originally from dairy food, enhances immune function following oral delivery in different milk bases.