Effect of probiotic Lactobacillus rhamnosus GG intervention on global serum lipidomic profiles in healthy adults

AIM： To investigate the effect of three weeks＇ intervention with a probiotic Lactobacillus rhamnosus GG （LGG） bacteria on global serum lipidomic profiles and evaluate whether the changes in inflammatory variables （CRP, TNF-α and IL-6） are reflected in the global lipidomic profiles of healthy adults. METHODS： We performed UPLC/MS-based global lipidomic platform analysis of serum samples （n = 26） in a substudy of a randomised, double-blind, placebo- controlled 3-wk clinical intervention trial investigating the immunomodulatory effects of probiotics in healthy adults. RESULTS： A total of 407 lipids were identified, corresponding to 13 different lipid classes. Serum samples showed decreases in the levels of lysophosphatidylcholines （LysoGPCho）, sphingomyelins （SM） and several glycerophosphatidylcholines （GPCho）, while triacylglycerols （TAG） were mainly increased in the probiotic LGG group during the intervention. Among the inflammatory variables, IL-6 was moderately associated by changes in global lipidomic profiles, with the top-ranked lipid associated with IL-6 being the proinflammatory LysoGPCho （20：4）. There was a weak association between the lipidomic profiles and the two other inflammatory markers, TNF-~ and CRP. CONCLUSION： This was the first study to investigate the effects of probiotic intervention on global lipidomic profiles in humans. There are indications that probiotic LGG intervention may lead to changes in serum global lipid profiles, as reflected in decreased GPCho, LysoGPCho and SM as well as mainly increased TAG.     

Lactobacillus rhamnosus probiotic prevents airway function deterioration and promotes gut microbiome resilience in a murine asthma model

ABSTRACT

Allergic asthma is a highly prevalent inflammatory disease of the lower airways, clinically characterized by airway hyperreactivity and deterioration of airway function. Immunomodulatory probiotic bacteria are increasingly being explored to prevent asthma development, alone or in combination with other treatments.

In this study, wild-type and recombinant probiotic Lactobacillus rhamnosus GR-1 were tested as preventive treatment of experimental allergic asthma in mice. Recombinant L. rhamnosus GR-1 was designed to produce the major birch pollen allergen Bet v 1, to promote allergen-specific immunomodulation. Administration of wild-type and recombinant L. rhamnosus GR-1 prevented the development of airway hyperreactivity. Recombinant L. rhamnosus GR-1 also prevented elevation of airway total cell counts, lymphocyte counts and lung IL-1β levels, while wild-type L. rhamnosus GR-1 inhibited airway eosinophilia. Of note, a shift in gut microbiome composition was observed after asthma development, which correlated with the severity of airway inflammation and airway hyperreactivity. In the groups that received L. rhamnosus GR-1, this asthma-associated shift in gut microbiome composition was not observed, indicating microbiome-modulating effects of this probiotic.

These data demonstrate that L. rhamnosus GR-1 can prevent airway function deterioration in allergic asthma. Bet v 1 expression by L. rhamnosus GR-1 further contributed to lower airway inflammation, although not solely through the expected reduction in T helper 2-associated responses, suggesting involvement of additional mechanisms. The beneficial effects of L. rhamnosus GR-1 correlate with increased gut microbiome resilience, which in turn is linked to protection of airway function, and thus further adds support to the existence of a gut-lung axis.     

The genome sequence of the probiotic intestinal bacterium Lactobacillus johnsonii NCC 533

Lactobacillus johnsonii NCC 533 is a member of the acidophilus group of intestinal lactobacilli that has been extensively studied for their "probiotic" activities that include, pathogen inhibition, epithelial cell attachment, and immunomodulation. To gain insight into its physiology and identify genes potentially involved in interactions with the host, we sequenced and analyzed the 1.99-Mb genome of L. johnsonii NCC 533. Strikingly, the organism completely lacked genes encoding biosynthetic pathways for amino acids, purine nucleotides, and most cofactors. In apparent compensation, a remarkable number of uncommon and often duplicated amino acid permeases, peptidases, and phosphotransferase-type transporters were discovered, suggesting a strong dependency of NCC 533 on the host or other intestinal microbes to provide simple monomeric nutrients. Genome analysis also predicted an abundance (>12) of large and unusual cell-surface proteins, including fimbrial subunits, which may be involved in adhesion to glycoproteins or other components of mucin, a characteristic expected to affect persistence in the gastrointestinal tract (GIT). Three bile salt hydrolases and two bile acid transporters, proteins apparently critical for GIT survival, were also detected. In silico genome comparisons with the >95% complete genome sequence of the closely related Lactobacillus gasseri revealed extensive synteny punctuated by clear-cut insertions or deletions of single genes or operons. Many of these regions of difference appear to encode metabolic or structural components that could affect the organisms competitiveness or interactions with the GIT ecosystem.     

In vitro study of the effect of a probiotic bacterium Lactobacillus rhamnosus against herpes simplex virus type 1

BackgroundDue to the emergence of drug resistance in herpes simplex virus type 1 (HSV-1), researchers are trying to find other methods for treating herpes simplex virus type 1 infections. Probiotic bacteria are effective in macrophage activation and may have antiviral activities.ObjectiveThis study aimed at verifying the direct effect of Lactobacillus rhamnosus, a probiotic bacterium, in comparison with Escherichia coli, a non-probiotic one, on HSV-1 infection, and determining its effect on macrophage activation for in vitro elimination of HSV-1 infection.MethodsThe above bacteria were introduced into HSV-1 infected Vero cells, and their effects were examined using both MTT and plaque assay. To determine macrophage activation against in vitro HSV-1 infection, J774 cells were exposed to these bacteria; then, macrophage viability was examined with the MTT method, and tumor necrosis factor alpha (TNF-α), Interferon-gamma (IFN-γ), and nitric oxide (NO) assessments were performed using the ELISA method.ResultsA significant increased viability of macrophages was observed (p < 0.05) in the presence of Lactobacillus rhamnosus before and after HSV-1 infection when compared with Escherichia coli as a non-probiotic bacterium. However, tumor necrosis factor α concentration produced by Escherichia coli-treated J774 cells was significantly higher than Lactobacillus rhamnosus-treated J774 cells (p < 0.05). Interferon-gamma and NO production were not different in the groups treated with Escherichia coli or with Lactobacillus rhamnosus.ConclusionThe results of this study indicate that Lactobacillus rhamnosus enhances macrophage viability for HSV-1 elimination and activation against HSV-1 more effectively, when compared with non-probiotic Escherichia coli. It also seems that receptor occupation of macrophage sites decreases HSV-1 infectivity by both of the studied bacteria.     

鼠李糖乳杆菌GG在心血管疾病中的研究进展

［摘要］　心血管疾病负担持续加重是目前全球面临的重大健康问题。靶向肠道菌群是降低心血管疾病发病率和病死率的潜在有效策略。近年来,益生菌疗法的兴起为心血管疾病的预防和治疗提供了新思路。鼠李糖乳杆菌GG（LGG）通过抗炎、抗氧化应激、调节肠道菌群和保护肠屏障等多种机制在心血管疾病的预防和治疗中展现出巨大的潜力。该文对近年来LGG在心血管疾病中的研究进展作一综述。     

Utility of stool culture in inpatient

Several studies have concluded that it is inappropriate to perform stool cultures (SC) to inpatients that have stayed hospitalized three days or more because nosocomial diarrhea is not due to enteric pathogenic bacteria that are searched through this exam. The aim of this paper was to analyze the SC yield performed to patients hospitalized in the UC Health Net since January to December 2002 and the rate of positive results obtained depending on the length of hospitalization in order to define if international guidelines are useful to the national reality. During twelve months 3474 SC were evaluated, 458 (13.2%) belonged to inpatients. Of them 16 (3.5%) were positive, 13 were obtained on the first day, 2 at the second day and 1 at the fifth day of hospitalization. Only 1/190 (0.5) SC obtained after two days of hospitalization yielded a positive result. These results reinforce the international recommendation of not performing SC to inpatients that have stayed more than three days at the hospital; besides, considering previous figures, we suggest to make a cutoff at day two of hospitalization, after two days there is no a significant clinical impact. This strategy means to reduce 41% of these analyses and to save the corresponding money.     

鼠李糖乳杆菌治疗肠易激综合征机制新进展

肠易激综合征(irritable bowel syndrome,IBS)是临床上常见的功能性胃肠病,其会影响患者的生活质量.因此探寻IBS的有效治疗方法具有重要意义.益生菌可改善IBS患者的症状并提高其生活质量,其中备受关注的是鼠李糖乳杆菌(Lactobacillus rhamnosus GG,LGG).LGG是目前被...     

鼠李糖乳杆菌GG防治消化系统疾病的研究进展

鼠李糖乳杆菌GG(LGG)是目前研究较广泛的益生菌之一,在人类胃肠道中具有良好的黏附及定植能力.LGG可通过多种途径起到保护胃肠道的作用,由于其独特的生物学功能,目前LGG已被用于预防和治疗多种胃肠道微生态失调相关疾病.该文就LGG防治消化系统疾病(包括幽门螺杆菌感染、急性感染性腹泻、旅行者腹泻、抗生素相关腹泻、功能性...     

Immobilization of cadmium and lead by Lactobacillus rhamnosus GR-1 mitigates apical-to-basolateral heavy metal translocation in a Caco-2 model of the intestinal epithelium

Heavy metals are highly toxic elements that contaminate the global food supply and affect human and wildlife health. Purification technologies are often too expensive or not practically applicable for large-scale implementation, especially in impoverished nations where heavy metal contamination is widespread. Lactobacillus rhamnosus GR-1 (LGR-1) was shown in previous work to reduce heavy metal bioaccumulation in a Tanzanian cohort of women and children through indeterminant mechanisms. Here, it was hypothesized that LGR-1 could sequester the heavy metals lead (Pb) and cadmium (Cd), thereby reducing their absorption across intestinal epithelium. LGR-1 and other lactobacilli significantly reduced the amount of Pb and Cd in solution at all concentrations tested (0.5 mg/L – 50 mg/L) and exhibited sustained binding profiles over a 48-hour period. Relative binding efficiency of LGR-1 decreased as Pb concentration increased, with an absolute minimum binding threshold apparent at concentrations of 2 mg/L and above. Electron microscopy revealed that Pb formed irregular cell-surface clusters on LGR-1, while Cd appeared to form intracellular polymeric clusters. Additionally, LGR-1 was able to significantly reduce apical-to-basolateral translocation of Pb and Cd in a Caco-2 model of the intestinal epithelium. These findings demonstrate the absorbent properties of LGR-1 can immobilize Pb and Cd, effectively reducing their translocation across the intestinal epithelium in vitro. Oral administration of heavy metal-binding Lactobacillus spp. (many of which are known human symbionts and strains of established probiotics) may offer a simple and effective means to reduce the amount of heavy metals absorbed from foods in contaminated regions of the world.     

肠道菌鉴定培养基的研究进展

目前,细菌学的分类和鉴定技术有了很大的发展,但是,临床上肠道菌鉴定主要还以生化反应为主.单管多用的显色培养基筛选微生物是一种较新的技术,其操作简便、特异性强,能提高微生物细菌鉴定在临床上的地位,单管多用的显色培养基的开发、应用是今后的发展趋势.     

Protective effect of Lactobacillus rhamnosus 231 against N-Methyl-N'-nitro-N-nitrosoguanidine in animal model

The protective effect of Lactobacillus rhamnosus 231 (Lr 231) against potent carcinogen N-Methyl-N'-Nitro-N-Nitrosoguanidine (MNNG) in the rat model is studied. Daily feeding with Lr 231 improved the body weight of male Wistar rats compared with control groups. Fecal azoreductase (p < 0.001) and nitroreductase (p < 0.01) enzyme activity decreased significantly in Lr 231 group in comparison with control groups that received only phosphate buffer or MNNG. Oral administration of MNNG led to a significant increase in Glutathione transferase (GST) while Glutathione reductase (GSH) showed decreased activity. Conversely, feeding Lr 231 showed significantly increased GSH and decreased GST activity in comparison to the MNNG group, emphasizing the protection provided by Lr 231 against MNNG. Histopathological analysis of liver, spleen and colon showed decreased signs of inflammation in the Lr 231 group. The present study highlights that inclusion of active Lr 231 in regular diets could be used to prevent MNNG induced colon carcinoma.     

鼠李糖乳杆菌干预肠道菌群及脂质代谢治疗代谢相关性脂肪性肝病的研究进展

代谢相关性脂肪性肝病(metabolic associated fatty liver disease, MAFLD)现已成为全世界最常见的慢性肝病,发病率在逐年增加,目前无临床特效药,其发病机制复杂,主要涉及肥胖、肠道菌群、胰岛素抵抗、环境、遗传等。近年来,益生菌在预防和治疗MAFLD中被广泛研究,鼠李糖乳杆菌(Lactobacillus rhamnosus, LGG)属乳杆菌属的经典益生菌菌株。大量研究证明,LGG可通过调节肠道菌群、改善肠黏膜屏障及降低胆固醇改善MAFLD。本文主要阐述LGG干预MAFLD的相关可能机制。     

Lactobacillus rhamnosus GG prevents epithelial barrier dysfunction induced by interferon-gamma and fecal supernatants from irritable bowel syndrome patients in human intestinal enteroids and colonoids

Disruption of intestinal barrier homeostasis is an important pathogenic factor in conditions such as irritable bowel syndrome (IBS). Lactobacillus rhamnosus GG (LGG) improves IBS symptoms through unclear mechanisms. Previous studies utilizing colorectal adenocarcinoma cell lines showed that LGG metabolites prevented interferon gamma (IFN-gamma) induced barrier damage but the model employed limited these findings. We aimed to interrogate the protective effects of LGG on epithelial barrier function using human intestinal epithelial cultures (enteroids and colonoids) as a more physiologic model. To investigate how LGG affects epithelial barrier function, we measured FITC-Dextran (FD4) flux across the epithelium as well as tight junction zonula occludens 1 (ZO-1) and occludin (OCLN) expression. Colonoids were incubated with fecal supernatants from IBS patients (IBS-FSN) and healthy controls in the presence or absence of LGG to examine changes in gut permeability. Enteroids incubated with IFN-gamma demonstrated a downregulation of OCLN and ZO-1 expression by 67% and 50%, respectively (p<0.05). This was accompanied by increased paracellular permeability as shown by leakage of FD4. Pretreatment of enteroids with LGG prevented these changes and normalized OCLN and ZO-1 to control levels. These actions were independent of its action against apoptosis. However, these protective effects were not seen with LGG cell wall extracts, LGG DNA, or denatured (boiled) LGG. Intriguingly, IBS-FSN injected into colonoids increased paracellular permeability, which was prevented by LGG. LGG, likely due to secreted proteins, protects against epithelial barrier dysfunction. Bacterial-derived factors to modulate gut barrier function may be a treatment option in disorders such as IBS.     

Effects of Lactobacillus rhamnosus GG and Lactobacillus reuteri R2LC on Acetic Acid-Induced Colitis in Rats

Background: Certain lactobacilli reduce the severity of experimental colitis. The aim of this study was to compare the effects of a human strain Lactobacillus rhamnosus GG and a rat strain Lactobacillus reuteri R2LC on acetic acid-induced colitis in rats. Methods:Lactobacillus rhamnosus GG, Lactobacillus reuteri R2LC or sulphasalazine were given orally to the rats. Colitis was assessed 72 h after induction with acetic acid. Results:Lactobacillus reuteri R2LC significantly antagonized body weight loss caused by inflammation compared with Lactobacillus rhamnosus GG and sulphasalazine, and oedema formation in the colon compared with sulphasalazine. Lactobacillus reuteri R2LC reduced the median value of macroscopic ulceration and the protein content of inducible nitric oxide synthase by 50% and the median of the protein content of inducible cyclooxygenase by 30% compared with that of the colitis control group, and Lactobacillus rhamnosus GG reduced the median of inducible nitric oxide protein content by 40% and increased the median of inducible cyclooxygenase protein content by 30% compared with the median value of the colitis control group, but these differences were not statistically significant. Conclusions: The rat strain Lactobacillus reuteri R2LC, but not the human strain Lactobacillus rhamnosus GG, is of benefit in reducing the severity of acetic acid-induced colitis in rats. These results suggest that it is not the total amount of Lactobacillus but the particular species or strain of Lactobacillus that is important in attenuating experimental colitis.     

Effect of probiotic Lactobacillus plantarum Dad-13 powder consumption on the gut microbiota and intestinal health of overweight adults

BACKGROUNDShifting on lifestyle, diet, and physical activity contributed on increasing number of obese people around the world. Multiple factors influence the development of obesity. Some research suggested that gut microbiota (GM) plays an important role in nutrient absorption and energy regulation of individuals, thus affecting their nutritional status. Report of Indonesia Basic Health Research showed that the prevalence of obesity in every province tended to increase. Although the root cause of obesity is excessive calorie intake compared with expenditure, the differences in gut microbial ecology between healthy and obese humans may affect energy homeostasis. GM affect body weight, especially obesity. Probiotics that are consumed while alive and able to colonize in the intestine are expected to increase the population of good bacteria, especially Bifidobacteria and Lactobacilli, and suppress pathogens such as Enterobacteriaceae and Staphylococcus. The strain of L. plantarum Dad-13 has been demonstrated to survive and colonize in the gastrointestinal tract of healthy Indonesian adults who consume fermented milk containing L. plantarum Dad-13. The consumption of probiotic L. plantarum Dad-13 powder decreased E. coli and non-E. coli coliform bacteria in school-aged children in Indonesia. L. plantarum is a dominant bacterium in the average Indonesian’s GM. For this reason, this bacterium is probably a more suitable probiotic for Indonesians.AIMTo determine the effect of the consumption of indigenous probiotic Lactobacillus plantarum Dad-13 powder in overweight adults in Yogyakarta (Indonesia).METHODSSixty overweight volunteers with a body mass index (BMI) equal to or greater than 25 consume indigenous probiotic powder L. plantarum Dad-13 (2 × 10⁹ CFU/gram/sachet) for 90 d. The study was a randomized, double-blind, placebo-controlled study. The volunteers filled in a diary on a daily basis, which consisted of questions on study product intake (only during ingestion period), other food intake, number of bowel movements, fecal quality (consistency and color), any medications received, and any symptom of discomfort, such as diarrhea, constipation, vomiting, gassing, sensation of illness, etc. Fecal samples and the subjects’ diaries were collected on the morning of day 10 + 1, which was marked as the end of the baseline period and the start of the ingestion period. During the ingestion period (from day 11 to day 101), several parameters to measure and analyze the results included body weight and height (once a month), the lipid profile, GM analysis using MiSeq, short-chain fatty acid (SCFA) analysis using gas chromatography, and the measurement of fecal pH using a pH meter.RESULTSThe consumption of indigenous probiotic powder L. plantarum Dad-13 caused the average body weight and BMI of the probiotic group to decrease from 84.54 ± 17.64 kg to 83.14 ± 14.71 kg and 33.10 ± 6.15 kg/m² to 32.57 ± 5.01 kg/m², respectively. No significant reduction of body weight and BMI in the placebo group was observed. An analysis of the microbiota showed that the number of Bacteroidetes, specifically Prevotella, increased significantly, while that of Firmicutes significantly decreased. No significant change in lipid profile in both groups was found. Also, no significant change in SCFAs (e.g., butyrate, propionate, acetic acid) and pH level was found after the consumption of the probiotic.CONCLUSIONNo significant differences in pH before and after ingestion were observed in both the probiotic and placebo groups as well as in the lipid profile of both cholesterol and triglyceride, high-density lipoprotein (HDL), low-density lipoprotein (LDL), and the LDL/HDL ratio. In addition, no significant changes in the concentration of SCFAs (e.g., acetic acid, propionate, and butyrate) were found after con-sumption. Interestingly, a significant decrease in body weight and BMI (P < 0.05) was determined in the treatment group. An analysis of GM shows that L. plantarum Dad-13 caused the Firmicutes population to decrease and the Bacteroidetes population (especially Prevotella) to increase.