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Gut lactobacilli and bifidobacteria on the immune homeostasis. Therefore, to understand the mechanism in vivo, we selected human fecal Lactobacillus rhamnosus NK210 and Bifidobacterium longum NK219, which strongly suppressed the IFN-γ to IL-10 expression (IIE) ratio in lipopolysaccharide-stimulated macrophages. Thereafter, we examined their effects on the endotoxin, antibiotics, or antitumor drug-stimulated immune imbalance in mice. Intraperitoneal injection of lipopolysaccharide and oral gavage of ampicillin increased IFN-γ and TNF-α expression in the spleen, colon, and hippocampus, while IL-10 expression decreased. However, intraperitoneal injection of cyclophosphamide suppressed IFN-γ, TNF-α, and IL-10 expression. LPS exposure induced splenic natural killer cell cytotoxicity against YAC-1 cells (sNK-C) and peritoneal macrophage phagocytosis against Candida albicans (pMA-P) activities, while cyclophosphamide and ampicillin treatments suppressed sNK-C and pMA-P activities. However, LPS, ampicillin, cyclophosphamide all increased IIE and TNF-α to IL-10 expression (TIE) ratios. Oral administration of NK210 and/or NK219 significantly reduced LPS-induced sNK-C, pMA-P, and IFN-γ expression, while cyclophosphamide- or ampicillin-suppressed sNK-C and pMA-P activities, cyclophosphamide-suppressed IFN-γ, TNF-α, and IL-10 expression, and ampicillin-suppressed IL-10 expression increased. Nevertheless, they suppressed LPS-, ampicillin-, or cyclophosphamide-induced IIE and TIE ratios, cognitive impairment, and gut dysbiosis. In particular, NK219, but not NK210, increased the IIE expression ratio in vitro and in vivo, and enhanced sNK-C and pMA-P activities in normal control mice, while cognitive function and gut microbiota composition were not significantly affected. These findings suggest that NK210, Lactobacillus sp, and NK219, Bifidobacterium additively or synergistically alleviate gut dysbiosis, inflammation, and cognitive impairment with immune imbalance by controlling IIE and TIE ratios., (© 2021. The Author(s).)

Feather pecking (FP) is a stress-induced neuropsychological disorder of birds. Intestinal dysbiosis and inflammation are common traits of these disorders. FP is, therefore, proposed to be a behavioral consequence of dysregulated communication between the gut and the brain. Probiotic bacteria are known to favorably modulate the gut microbiome and hence the neurochemical and immune components of the gut-brain axis. Consequently, probiotic supplementation represents a promising new therapeutic to mitigate widespread FP in domestic chickens. We monitored FP, gut microbiota composition, immune markers, and amino acids related to the production of neurochemicals in chickens supplemented with Lactobacillus rhamnosus or a placebo. Data demonstrate that, when stressed, the incidence of FP increased significantly; however, L. rhamnosus prevented this increase. L. rhamnosus supplementation showed a strong immunological effect by increasing the regulatory T cell population of the spleen and the cecal tonsils, in addition to limiting cecal microbiota dysbiosis. Despite minimal changes in aromatic amino acid levels, data suggest that catecholaminergic circuits may be an interesting target for further studies. Overall, our findings provide the first data supporting the use of a single-strain probiotic to reduce stress-induced FP in chickens and promise to improve domestic birds' welfare., (© 2021. The Author(s).)

Background: Necrotizing enterocolitis (NEC) is one of the most serious complications in preterm infants. Probiotics have been used to prevent NEC. Safety is a major concern for this practice., Methods: We reported a female preterm infant who received oral Lactobacillus rhamnosus GG but developed sepsis 12 days after the treatment. Cultures of blood and the catheter tip yielded L. rhamnosus. Next-generation sequencing was performed to analyze isolates from blood, stool, catheter, and product capsules. We also determined the capacities of these isolates to form biofilms. A literature review was performed., Results: The patient was treated with ampicillin and piperacillin/tazobactam, and she subsequently recovered without complications. The analysis of genome sequences indicated that all the isolates belonged to the clone of L. rhamnosus GG (ATCC 53103), suggesting that sepsis was a catheter-related infection caused by the oral probiotic. L. rhamnosus GG (ATCC 53103) and the probiotic strain tested formed biofilms under all growth conditions. Isolates from the blood and catheter tip also formed biofilms, but the stool isolate did not. The capacity of intrinsic biofilm formation in L. rhamnosus GG depended on environmental factors and the type of culture medium. Literature review of L. rhamnosus GG sepsis in preterm and young infants found that nearly 60% of the patients had a suspected or confirmed infected catheter., Conclusion: The study showed that the capacity of L. rhamnosus GG to form biofilms, especially in the presence of glucose, is a critical factor leading to the probiotic-related sepsis in preterm infants., Competing Interests: Declaration of Competing Interest The authors declare no conflicts of interest., (Copyright © 2020. Published by Elsevier B.V.)

Osteoarthritis (OA) is the most common form of arthritis and age-related degenerative joint disorder, which adversely affects quality of life and causes disability. However, the pathogenesis of OA remains unclear. This study was performed to examine the effects of Lactobacillus rhamnosus in OA progression. OA was induced in 6-week-old male Wistar rats by monosodium iodoacetate (MIA) injection, and the effects of oral administration of L. rhamnosus were examined in this OA rat model. Pain severity, cartilage destruction, and inflammation were measured in MIA-induced OA rats. The small intestines were isolated from OA rats, and the intestinal structure and inflammation were measured. Protein expression in the dorsal root ganglion was analyzed by immunohistochemistry. The effects of L. rhamnosus on mRNA and protein expression in chondrocytes stimulated with interleukin (IL)-1β and lipopolysaccharide (LPS) were analyzed by real-time polymerase chain reaction (RT-PCR) and enzyme-linked immunosorbent assay (ELISA). Pain severity was decreased in L. rhamnosus -treated MIA-induced OA rats. The levels of expression of MCP-1, a potential inflammatory cytokine, and its receptor, CCR2, were decreased, and GABA and PPAR-γ expression were increased in L. rhamnosus -treated OA rats. The inflammation, as determined by IL-1β, and cartilage destruction, as determined by MMP3, were also significantly decreased by L. rhamnosus in OA rats. Additionally, intestinal damage and inflammation were improved by L. rhamnosus. In human OA chondrocytes, TIMP1, TIMP3, SOX9, and COL2A1 which are tissue inhibitors of MMP, and IL-10, an anti-inflammatory cytokine, were increased by L. rhamnosus . L. rhamnosus treatment led to decreased pain severity and cartilage destruction in a rat model of OA. Intestinal damage and inflammation were also decreased by L. rhamnosus treatment. Our findings suggested the therapeutic potential of L. rhamnosus in OA.

Background: The origin of most of the Lactobacillus rhamnosus genome sequences lodged in NCBI can be traced to food and faecal isolates followed by blood and tissue sites but with minimal representation from oral and vaginal isolates. However, on the L. rhamnosus phylogenetic tree no apparent clade is linked to the origin of isolation or to the relevant clinical source, except for a distinct clade exclusively shared by L. rhamnosus isolates from early stages of dental pulp infection (LRHMDP2 and LRHMDP3) and from bronchoalveolar lavage (699_LRHA and 708_LRHA) from a critical care patient. These L. rhamnosus strains, LRHMDP2, LRHMDP3, 699_LRHA and 708_LRHA isolated from different continents, display closest genome neighbour gapped identity of 99.95%. The aim of this study was to define a potentially unique complement of genes of clinical relevance shared between these L. rhamnosus clinical isolates in comparison to probiotic L. rhamnosus strains., Results: In this analysis we used orthologous protein identification tools such as ProteinOrtho followed by tblastn alignments to identify a novel tyrosine protein phosphatase (wzb)-tyrosine-protein kinase modulator EpsC (wzd)- synteny exopolysaccharide (EPS) cluster. This EPS cluster was specifically conserved in a clade of 5 clinical isolates containing the four L. rhamnosus clinical isolates noted above and Lactobacillus spp. HMSC077C11, a clinical isolate from a neck abscess. The EPS cluster was shared with only two other strains, L. rhamnosus BPL5 and BPL15, which formed a distant clade on the L. rhamnosus phylogenetic tree, with a closest genome neighbour gapped identity of 97.51% with L. rhamnosus LRHMDP2 and LRHMDP3. Exclusivity of this EPS cluster (from those identified before) was defined by five EPS genes, which were specifically conserved between the clade of 5 clinical isolates and L. rhamnosus BPL5 and BPL15 when compared to the remaining L. rhamnosus strains. Comparative genome analysis between the clade of 5 clinical isolates and L. rhamnosus BPL5 and BPL15 showed a set of 58 potentially unique genes characteristic of the clade of 5., Conclusion: The potentially unique functional protein orthologs associated with the clade of 5 clinical isolates may provide understanding of fitness under selective pressure.

By modulating the human gut microbiome, prebiotics and probiotics (combinations of which are called synbiotics) may be used to treat diseases such as colorectal cancer (CRC). Methodological limitations have prevented determining the potential combinatorial mechanisms of action of such regimens. We expanded our HuMiX gut-on-a-chip model to co-culture CRC-derived epithelial cells with a model probiotic under a simulated prebiotic regimen, and we integrated the multi-omic results with in silico metabolic modeling. In contrast to individual prebiotic or probiotic treatments, the synbiotic regimen caused downregulation of genes involved in procarcinogenic pathways and drug resistance, and reduced levels of the oncometabolite lactate. Distinct ratios of organic and short-chain fatty acids were produced during the simulated regimens. Treatment of primary CRC-derived cells with a molecular cocktail reflecting the synbiotic regimen attenuated self-renewal capacity. Our integrated approach demonstrates the potential of modeling for rationally formulating synbiotics-based treatments in the future., (Copyright © 2019 The Author(s). Published by Elsevier Inc. All rights reserved.)

An optimal gut microbiota influences many beneficial processes in the metazoan host. However, the molecular mechanisms that mediate and function in symbiont-induced host responses have not yet been fully characterized. Here, we report that cellular ROS enzymatically generated in response to contact with lactobacilli in both mice and Drosophila has salutary effects against exogenous insults to the intestinal epithelium via the activation of Nrf2 responsive cytoprotective genes. These data show that the xenobiotic-inducible Nrf2 pathway participates as a signaling conduit between the prokaryotic symbiont and the eukaryotic host. Indeed, our data imply that the capacity of lactobacilli to induce redox signaling in epithelial cells is a highly conserved hormetic adaptation to impel cellular conditioning to exogenous biotic stimuli. These data also highlight the role the microbiota plays in eukaryotic cytoprotective pathways and may have significant implications in the characterization of a eubiotic microbiota., (Copyright © 2015 The Authors. Published by Elsevier Inc. All rights reserved.)

This study aimed to evaluate the capacity of Lactobacillus rhamnosus and/or its products to induce the synthesis of cytokines (TNF-α, IL-1β, IL-4, IL-6, IL-10, and IL-12) by mouse macrophages (RAW 264.7). Three microorganism preparations were used: live L. rhamnosus (LLR) suspension, heat-killed L. rhamnosus (HKLR) suspension, and the supernatant of a heat-killed L. rhamnosus (SHKLR) suspension, which were cultured with macrophages (37°C, 5% CO2) for 2 h and 30 min. After that, cells were cultured for 16 h. The supernatants were used for the quantitation of cytokines, by ELISA. The results were compared with the synthesis induced by lipopolysaccharide (LPS) and analysed, using ANOVA and Tukey test, 5%. LLR and HKLR groups were able to significantly increase the production of TNF-α, IL-6, and IL-10 (P < 0.05). SHKLR also significantly increased the production of TNF-α and IL-10 (P < 0.05) but not IL-6 (P > 0.05). All the L. rhamnosus suspensions were not able to produce detectable levels of IL-1β or significant levels of IL-4 and IL-12 (P > 0.05). In conclusion, live and heat-killed L. rhamnosus suspensions were able to induce the synthesis of different cytokines with proinflammatory (TNF-α and IL-6) or regulatory (IL-10) functions, suggesting the role of strain L. rhamnosus ATCC 7469 in the modulation or in the stimulation of immune responses.

Probiotic strains of Lactobacillus are currently used in a variety of clinical practices with limited evidence to support their use. Lactobacillus species are a normal part of gastrointestinal flora, and bacteremia with probiotic strains of Lactobacillus is very uncommon. We describe a case of Lactobacillus bacteremia in a 17-year-old boy with ulcerative colitis managed with systemic corticosteroids and infliximab, who presented with fever to 102°F, flushing, and chills 1 week after starting Lactobacillus rhamnosus GG probiotics. Initial blood culture on day 2 of his fever was positive for Lactobacillus, however, subsequent blood cultures on day 3 and 5 were negative. He was treated empirically with antibiotics for 5 days and defervesced by day 8 of his illness. 16 S rRNA sequence analysis identified the organism from the patient's blood culture and probiotic capsule as L. rhamnosus with a 99.78% match for both the strains. This case report highlights the potential risk of Lactobacillus bacteremia in immunosuppressed patients with severe active ulcerative colitis.

Lactobacillus spp. are ubiquitous commensals of the normal human flora that are only occasionally found in clinical infections. Their role in human disease is established for infectious endocarditis but is controversial for other infections. We sought to characterize clinically associated Lactobacillus spp. We conducted a retrospective study, which consisted of the screening of Lactobacillus isolates obtained in our laboratory from January 2004 to December 2009. The polymerase chain reaction (PCR) assay was selected as the gold standard method. The isolates were first identified using API Coryne strips, matrix-assisted laser desorption/ionization time-of-flight mass spectrometry (MALDI-TOF MS), and 16S rRNA gene sequencing. Lactobacillus tuf gene-based identification was used when the 16S rRNA results were inconclusive. Among the 60 strains of Lactobacillus spp. obtained in our laboratory, L. rhamnosus was the most commonly isolated species and was found in blood cultures from 16 patients. Combined with 45 patients reported in the literature, we found that patients presenting with L. rhamnosus bacteremia experienced nosocomial infections associated with both immunosuppression (66 %) and catheters (83 %).

We investigated the consequences of feeding with a Lactobacillus species on the immune environment in GALT, and the role of dendritic cells and heme oxygenase-1 in mediating these responses. Feeding with a specific strain of Lactobacillus rhamnosus induced a significant increase in CD4+CD25+Foxp3+ functional regulatory T cells in GALT. This increase was greatest in the mesenteric lymph nodes and associated with a marked decrease in TNF and IFNγ production. Dendritic cell regulatory function and HO-1 expression was also increased. The increase in Foxp3+ T cells could be prevented by treatment with a heme oxygenase inhibitor. However, neither inhibition of heme oxygenase nor blockade of IL-10 and TGFβ prevented the inhibition of inflammatory cytokine production. In conclusion Lactobacillus feeding induced a tolerogenic environment in GALT. HO-1 was critical to the enhancement of Foxp3+ regulatory T cells while additional, as yet unknown, pathways were involved in the down-regulation of inflammatory cytokine production by T cells.

A 24-year-old female patient developed sepsis resulting from preoperative administration of probiotics following an aortic valve replacement. Blood cultures revealed the causative agent to be the probiotic Lactobacillus rhamnosus, which has recently been implicated as an emerging aetiology of infection in those taking probiotics. In the past few years, probiotic use in hospitals has increased greatly. However, there is growing global evidence that the use of probiotics in patients with organ failure, immunocompromised status and dysfunctional gut barrier mechanisms can cause infections. This and other reports show the importance of establishing generally recognized safety guidelines., (© 2011 The Authors. Clinical Microbiology and Infection © 2011 European Society of Clinical Microbiology and Infectious Diseases.)

Introduction: Studies with a follow-up of < 8 weeks have indicated immune-preserving effects of yogurt probiotic supplementation among HIV patients. To evaluate the impact of 25 weeks use of probiotics, a randomized, double blind, controlled study was undertaken on 65 women who were naïve to anti-retroviral treatment., Results: Ten participants were excluded post-randomization due to non-eligibility. Thirty participants were assigned placebo, of whom 25 completed the study versus 19 of 25 completing the study in the probiotics group (p = 0.5). From baseline to 10 weeks follow-up, the CD4 count declined on average 3 CD4 cells/μl (95% Confidence Interval: -97; 91) with placebo versus an increase of 50 cells/μl (95% CI: -61; 162) with probiotics (p = 0.5). From baseline to 25 weeks, the CD4 count increased with 19 cells/μl (95% CI: -90; 129) in the placebo group versus 46 cells/μl (95% CI: -100; 192) with probiotics (p = 0.8). No differences in immune markers, diarrhea incidence or adverse events were observed., Discussion: Lactobacillus GR-1 and RC-14 may be safely consumed at 2 x 10(9) CFU/day by moderately immune compromised HIV patients but this did not universally preserve immune-function., Patients and Methods: Women were randomized to receive oral capsules containing Lactobacillus rhamnosus GR-1 and Lactobacillus reuteri RC-14 (2 x 10(9) colony forming units) or placebo twice daily for 25 weeks. The CD4 count and immune markers (IgG, IgE, IFNγ and IL-10) were measured at baseline and during follow-up, the occurrence of diarrhea was reported daily.

Organisms contained in probiotics are generally regarded as non-pathogenic and safe to administer. However, increasing reports of probiotic-associated infection raise concern over the safety of these products. We report a case of Lactobacillus empyema in a human immunodeficiency virus-infected lung transplant recipient receiving a probiotic containing Lactobacillus rhamnosus GG. We compare the epidemiology of Lactobacillus infections in heart and lung transplant recipients at our institution before and after the introduction of this probiotic, and discuss the potential mechanism for Lactobacillus within the probiotic to cause infections and disseminate., (© 2010 John Wiley & Sons A/S.)

The potential pathogenicity of selected (potentially) probiotic and clinical isolates of Lactobacillus rhamnosus and Lactobacillus paracasei was investigated in a rat model of experimental endocarditis. In addition, adhesion properties of the lactobacilli for fibrinogen, fibronectin, collagen and laminin, as well as the killing activity of the platelet-microbicidal proteins fibrinopeptide A (FP-A) and connective tissue activating peptide 3 (CTAP-3), were assessed. The 90 % infective dose (ID(90)) of the L. rhamnosus endocarditis isolates varied between 10(6) and 10(7) c.f.u., whereas four of the six (potentially) probiotic L. rhamnosus isolates showed an ID(90) that was at least 10-fold higher (10(8) c.f.u.) (P<0.001). In contrast, the two other probiotic L. rhamnosus isolates exhibited an ID(90) (10(6) and 10(7) c.f.u.) comparable to the ID(90) of the clinical isolates of this species investigated (P>0.05). Importantly, these two probiotic isolates shared the same fluorescent amplified fragment length polymorphism cluster type as the clinical isolate showing the lowest ID(90) (10(6) c.f.u.). L. paracasei tended to have a lower infectivity than L. rhamnosus (ID(90) of 10(7) to > or =10(8) c.f.u.). All isolates had comparable bacterial counts in cardiac vegetations (P>0.05). Except for one L. paracasei strain adhering to all substrates, all tested lactobacilli adhered only weakly or not at all. The platelet peptide FP-A did not show any microbicidal activity against the tested lactobacilli, whereas CTAP-3 killed the majority of the isolates. In general, these results indicate that probiotic lactobacilli display a lower infectivity in experimental endocarditis compared with true endocarditis pathogens. However, the difference in infectivity between L. rhamnosus endocarditis and (potentially) probiotic isolates could not be explained by differences in adherence or platelet microbicidal protein susceptibility. Other disease-promoting factors may exist in these organisms and warrant further investigation.

The objective of the present study was to determine the incidence of lactobacilli-induced bacteraemia in Stockholm, Sweden, between January 1998 and March 2004, and to identify the possible presence of probiotic strains. Isolated strains were checked for growth on selective lactobacilli-agar and the biochemical profiles were determined. The lactobacilli strains were further analysed with molecular methodologies to ascertain eventual similarities with the probiotic strains Lactobacillus paracasei subsp. paracasei F19 (LMG P 17806), Lactobacillus acidophilus NCFB 1748 and Lactobacillus rhamnosus GG (ATCC 53103). The minimum inhibitory concentrations of selected antimicrobial agents were determined by the agar dilution method. The incidence of bacteraemia cases caused by lactobacilli remained at the same level during the study period and constituted to <1% of the total number of bacteraemia cases each y. L. paracasei subsp. paracasei F19, L. acidophilus NCFB 1748 and L. rhamnosus GG were not identified in any of the samples.