Heat-Killed Levilactobacillus brevis as a Candidate Postbiotics Through Immunostimulation Mediated by Macrophage-Inducible C-Type Lectin.

To understand the beneficial health-promoting effects of lactic acid bacteria (LAB) on immune cells, it is necessary to understand the relationship between LAB and innate immune receptors. We investigated the possible involvement of C-type lectin receptors (CLRs) in the immune-stimulating function of LAB in several strains. We found that levels of interleukin (IL)-6, tumor necrosis factor (TNF)-α, and IL-10 were reduced by the addition of inhibitors for spleen tyrosine kinase (syk), a signaling molecule used by several CLRs. Furthermore, employing CLR-Fc fusion proteins and reporter cells, we found that macrophage-inducible C-type lectin (Mincle) binds to Levilactobacillus brevis strain La37. Interestingly, this interaction was only observed in heat-killed L. brevis and disappeared after proteinase K treatment. Seven strains of L. brevis from different sources were also examined; among them, six strains showed Mincle reactivity, and the characteristics of the ligand were similar to those of La37. These results may facilitate a better understanding of the immunomodulatory effects of LAB for the development of functional foods.

Infection-Induced Elevated Plasma Perampanel in a Patient with Hemimegalencephaly.

Perampanel is a noncompetitive, α-amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid glutamate receptor antagonist. Herein, we report a case of increased perampanel plasma concentration and impaired consciousness triggered by an infection. The patient had refractory epilepsy associated with hemimegalencephaly. During adolescence, perampanel (maximum dose, 10 mg, oral), valproic acid, clobazam, and lacosamide were administered for seizure control. He was admitted to our hospital with high fever, impaired consciousness, and elevated perampanel plasma level (from 1,300 to 1,790 ng/mL), but with no increase in the concentration of other antiseizure medications. Further examinations (blood, cerebrospinal fluid, brain magnetic resonance images, and electroencephalogram) revealed no physical cause for impaired consciousness. After discontinuation of perampanel, his level of consciousness gradually improved. The pharmacokinetics of perampanel may be modified by both hemimegalencephaly and infection, resulting in an elevated plasma concentration of perampanel. This case underlines the importance of monitoring perampanel plasma concentration in patients with underlying brain disease who develop an infection.

Newborn screening for Gaucher disease in Japan.

Gaucher disease (GD) is an autosomal recessive inborn metabolic disorder caused by a glucocerebrosidase (GCase) defect. GD is classified into three main types depending on accompanying neurological symptoms. Enzyme replacement therapy and substrate reduction therapy are limited in the treatment of neurological symptoms, and using genotype and GCase activity to discriminate between non-neuronopathic and neuronopathic GD may be challenging as the two sometimes phenotypically overlap. The number of patients exhibiting neurological symptoms in Japan is significantly higher than that in Europe and the United States, and newborn screening (NBS) is still not actively performed in Japan. Definitive determination of the actual frequency and proportion of the type of GD from the results of NBS remains inconclusive. We performed NBS for Fabry disease, Pompe disease, and GD, mainly in the Kyushu area in Japan. Herein, we discuss the results of NBS for GD, as well as, the insights gained from following the clinical course of patients diagnosed through NBS. A total of 155,442 newborns were screened using an enzyme activity assay using dried blood spots. We found four newborns showing lower GCase activity and were definitively diagnosed with GD by GBA gene analysis. The frequency of GD diagnosis through NBS was 1 in 77,720 when limited to the probands. This frequency is higher than that previously estimated in Japan. In the future, NBS for GD is expected to be performed in many regions of Japan and contribute to detecting more patients with GD. Early screening and diagnosis may have a very significant impact on the quality of life and potentially longevity in infants with GD.

Phenotypes of SMA patients retaining SMN1 with intragenic mutation.

BACKGROUND: Spinal muscular atrophy (SMA) is an autosomal recessive neuromuscular disorder caused by homozygous deletion or intragenic mutation of the SMN1 gene. It is well-known that high copy number of its homologous gene, SMN2, modifies the phenotype of SMN1-deleted patients. However, in the patients with intragenic SMN1 mutation, the relationship between phenotype and SMN2 copy number remains unclear. METHODS: We have analyzed a total of 515 Japanese patients with SMA-like symptoms (delayed developmental milestones, respiratory failures, muscle weakness etc.) from 1996 to 2019. SMN1 and SMN2 copy numbers were determined by quantitative polymerase chain reaction (PCR) method and/or multiplex ligation-dependent probe amplification (MLPA) method. Intragenic SMN1 mutations were identified through DNA and RNA analysis of the fresh blood samples. RESULTS: A total of 241 patients were diagnosed as having SMA. The majority of SMA patients showed complete loss of SMN1 (n = 228, 95%), but some patients retained SMN1 and carried an intragenic mutation in the retaining SMN1 (n = 13, 5%). Ten different mutations were identified in these 13 patients, consisting of missense, nonsense, frameshift and splicing defect-causing mutations. The ten mutations were c.275G > C (p.Trp92Ser), c.819_820insT (p.Thr274Tyrfs*32), c.830A > G (p.Tyr277Cys), c.5C > T (p.Ala2Val), c.826 T > C (p.Tyr276His), c.79C > T (p.Gln27*), c.188C > A (p.Ser63*), c.422 T > C (p.Leu141Pro), c.835-2A > G (exon 7 skipping) and c.835-3C > A (exon 7 skipping). It should be noted here that some patients with milder phenotype carried only a single SMN2 copy (n = 3), while other patients with severe phenotype carried 3 SMN2 copies (n = 4). CONCLUSION: Intragenic mutations in SMN1 may contribute more significantly to clinical severity than SMN2 copy numbers.

Immunobiotic Feed Developed with Lactobacillus delbrueckii subsp. delbrueckii TUA4408L and the Soymilk By-Product Okara Improves Health and Growth Performance in Pigs.

Lactobacillus delbrueckii subsp. delbrueckii TUA4408L is able to differentially modulate the innate immune response of porcine intestinal epithelial cells triggered by TLR4 activation. This strain also has a remarkable ability to grow on plant substrates. These two immunological and biotechnological characteristics prompted us to evaluate whether the soymilk by-product okara fermented with the TUA4408L strain can serve as an immunobiotic feed with the ability to beneficially modulate the intestinal immunity of piglets after weaning to improve their productivity. Our in vivo studies demonstrated that the administration of immunobiotic TUA4408L-fermented okara feed significantly increased piglet growth performance and meat quality. These positive effects were associated with the ability of the TUA4408L-fermented okara feed to beneficially modulate both intestinal microbiota and immunity in pigs. The immunobiotic feed improved the abundance of the beneficial bacteria Lactobacillus and Lactococcus in the gut of pigs, reduced blood markers of inflammation, and differentially regulated the expression of inflammatory and regulatory cytokines in the intestinal mucosa. These findings indicate that the immunobiotic TUA4408L-fermented okara feed could be an economical and environmentally friendly option to improve the growth performance and immune health of pigs.

Effect of Dietary Supplementation of Immunobiotic Lactiplantibacillusplantarum N14 Fermented Rakkyo (Allium chinense) Pickled Juice on the Immunocompetence and Production Performance of Pigs.

Rakkyo (Allium chinense), is a Japanese leek that is primarily used to make a popular sweet or sour pickled dish. Lactic acid bacteria are often involved in the preparation steps of fermented pickles, which helps in the effective preservation of the natural bioactive compounds of fruits and vegetable, and thereby exert several health benefits including immunomodulation and growth performance. This work aimed to evaluate the in vivo effects of adding Lactiplantibacillus plantarum N14 fermented rakkyo pickled juice as feed supplement on the immunocompetence and production performance of pigs. We first analyzed the nutritional composition, which revealed that the proportion of protein, lipid, and water-soluble fiber content were estimated as of 4%, 5%, and 5% in rakkyo residual liquid or juice, while 22%, 15% and 14%, respectively, were estimated in rakkyo residual powder. For the in vivo feeding trials, three groups of pigs were treated either with 5%, 20%, or 40% mixture (v/v) of fermented rakkyo pickled juice and the grinded residual liquid supplemented in the drinking water in addition to standard feed. The results of the feeding trials showed that the administration of a juice mixture of 5% or 20% (fermented pickled juice and residual liquid) had a similar trend of effects in improving the complement activity, phagocytic activity and leucocytes counts in the peripheral blood when compared to pigs fed with 40% mixture or untreated controls. Those changes were related to an improved resistance to enteric infections. Moreover, animals receiving a mixture of fermented pickled juice and fermented rakkyo residues had a higher growth rate and carcass quality than controls. The results suggested that the use of 5% mixture of fermented rakkyo pickled juice and the residual liquid through drinking water could be a cost-effective approach to promote the immune-health and production performance of pigs. This approach would contribute not only to the sustainable management of food wastes but also to the application of a value-added feed supplement for the promotion of animal health and production.

Ovalbumin-Induced Airway Inflammation Is Ameliorated in Dectin-1-Deficient Mice, in Which Pulmonary Regulatory T Cells Are Expanded through Modification of Intestinal Commensal Bacteria.

Asthma is an allergic chronic respiratory disease that affects more than 300 million people around the world. Dysbiosis of intestinal commensal microbiota influences the development of asthma. Dectin-1 (gene symbol: Clec7a), a C-type lectin receptor, plays an important role in the intestinal immune homeostasis by controlling regulatory T (Treg) cell differentiation through regulation of intestinal microbiota. However, it is not clear whether intestinal immune conditions affect immune responses in other organs. In this study, we examined the effects of Dectin-1 deficiency on allergic airway inflammation (AAI). OVA-induced AAI was attenuated in Clec7a -/- mice. Treg cells were more abundant in colonic lamina propria, mesenteric lymph nodes, and bronchoalveolar lavage fluid of Clec7a -/- mice after AAI induction. Treatment with antibiotics, but not an antifungal agent, decreased the abundance of intestinal Treg cells and aggravated the symptoms of AAI in Clec7a -/- mice. Transplantation of gut microbiota from Clec7a -/- mice into antibiotic-treated hosts increased the abundance of intestinal Treg cells and ameliorated AAI. Overcolonization by Lactobacillus murinus, a Dectin-1 signaling-regulated commensal bacterium, also promoted expansion of Treg cells in the colon and suppressed lung inflammation. Depletion of Treg cells with anti-CD25 Ab eliminated the phenotypic differences between wild-type and Clec7a -/- mice in OVA-induced AAI. These observations suggest that inhibition of Dectin-1 signaling ameliorates AAI by increasing the abundance of Treg cells in lungs through modification of intestinal commensal bacteria, suggesting a role for commensal microbiota in regulating inflammation in organs other than the intestine.

POLR1C variants dysregulate splicing and cause hypomyelinating leukodystrophy.

OBJECTIVE: To further clarify the molecular pathogenesis of RNA polymerase III (Pol III)-related leukodystrophy caused by biallelic POLR1C variants at a cellular level and potential effects on its downstream genes. METHODS: Exome analysis and molecular functional studies using cell expression and long-read sequencing analyses were performed on 1 family with hypomyelinating leukodystrophy showing no clinical and MRI findings characteristic of Pol III-related leukodystrophy other than hypomyelination. RESULTS: Biallelic novel POLR1C alterations, c.167T>A, p.M56K and c.595A>T, p.I199F, were identified as causal variants. Functional analyses showed that these variants not only resulted in altered protein subcellular localization and decreased protein expression but also caused abnormal inclusion of introns in 85% of the POLR1C transcripts in patient cells. Unexpectedly, allelic segregation analysis in each carrier parent revealed that each heterozygous variant also caused the inclusion of introns on both mutant and wild-type alleles. These findings suggest that the abnormal splicing is not direct consequences of the variants, but rather reflect the downstream effect of the variants in dysregulating splicing of POLR1C, and potentially other target genes. CONCLUSIONS: The lack of characteristic clinical findings in this family confirmed the broad clinical spectrum of Pol III-related leukodystrophy. Molecular studies suggested that dysregulation of splicing is the potential downstream pathomechanism for POLR1C variants.

IL-12p40 gene expression in lung and hilar lymph nodes of MPS-resistant pigs.

Mycoplasma pneumonia of swine (MPS) is caused by Mycoplasma hyopneumoniae (M.hp) and is a common chronic respiratory disease of pigs. Recently, a genetically selected variant of the Landrace pig (Miyagino L2) has a lower incidence of pulmonary MPS lesions. We investigated the pathological and immunological characteristics of MPS resistance in these pigs (n = 24) by comparing with the normal landrace pig (control: n = 24). The pathological MPS lung lesion score in MPS-selected landrace pigs was significantly lower than in the control. The gene expression of interleukin (IL)-12p40, which acts as a chemoattractant and a component of the bioactive cytokines IL-12 and IL-23, was significantly higher at the hilar lymph nodes, lung, and spleen in MPS-selected landrace pigs than in control landrace pigs, and these were negatively correlated with the macroscopic MPS lung lesion score. In summary, we demonstrate that resistance against MPS in Miyagino L2 pigs is associated with IL-12p40 up-regulation, in comparison with normal landrace pigs without the MPS vaccine. In addition, a comparative study of macroscopic MPS lung lesions and IL-12p40 gene expression in lung and hilar lymph nodes may lead to beneficial selection traits for the genetic selection for MPS resistance in pigs.

Addition of Wakame seaweed (Undaria pinnatifida) stalk to animal feed enhances immune response and improves intestinal microflora in pigs.

This study was conducted to evaluate the effects of supplementation of Wakame seaweed stalks on the immunity and intestinal microflora of pigs. Three separate experiments were performed: Relatively young (start at 20-30 kg; Experiments 1 and 2) and fattening period (70 kg; Experiment 3). All pigs (including the control group) were fed the same commercial feed, free from antibiotic additives, but in the feed for the treatment groups, 1% seaweed powder was added. There were no group differences observed in daily weight gain and feed intake in Experiments 1 and 2 between groups; however, daily weight gain was significantly higher in the treatment group compared to the control group in Experiment 3. The percentage of peripheral blood natural killer cells of the treatment group was significantly higher than that of the control group in all experiments. Although addition of seaweed changed the gene expression of cytokine and toll-like receptors of the small intestinal Peyer's patches slightly, seaweed seems to alter intestinal microflora preferentially, for instance, there was an increase in Lactobacillus and a decrease of Escherichia coli observed. These results suggest that Wakame seaweed can be used as supplement for pig feed to improve the gut health and immunity of pigs.

Suppression of IL-17F, but not of IL-17A, provides protection against colitis by inducing Treg cells through modification of the intestinal microbiota.

The cytokines IL-17A and IL-17F have 50% amino-acid identity and bind the same receptor; however, their functional differences have remained obscure. Here we found that Il17f-/- mice resisted chemically induced colitis, but Il17a-/- mice did not, and that Il17f-/- CD45RBhiCD4+ T cells induced milder colitis in lymphocyte-deficient Rag2-/- mice, accompanied by an increase in intestinal regulatory T cells (Treg cells). Clostridium cluster XIVa in colonic microbiota capable of inducing Treg cells was increased in both Il17f-/- mice and mice given transfer Il17f-/- T cells, due to decreased expression of a group of antimicrobial proteins. There was substantial production of IL-17F, but not of IL-17A, not only by naive T cells but also by various colon-resident cells under physiological conditions. Furthermore, antibody to IL-17F suppressed the development of colitis, but antibody to IL-17A did not. These observations suggest that IL-17F is an effective target for the treatment of colitis.

Effects of mycoplasmal pneumonia of swine (MPS) lung lesion-selected Landrace pigs on MPS resistance and immune competence in three-way crossbred pigs.

To clarify the genetic influence of mycoplasmal pneumonia of swine (MPS) lesion-selected Landrace (La) on MPS resistance and immune characteristics in three-way crossbred pigs (LaWaDa), the LaWaDa pigs were compared with the non-selected crossbred (LbWbDb) and purebred (La) pigs. The MPS lesion score in the three lines was as follows: La line < LaWaDa line < LbWbDb line, with significant differences among the lines. The proportions of myeloid cells and T cells were lower and higher, respectively, in the LaWaDa pigs compared with those in the other two lines. Messenger RNA (mRNA) expression of interleukin (IL)-6, IL-10, transforming growth factor-ß, and interferon-γ in peripheral blood was significantly increased after vaccination in the La and LaWaDa lines. IL-4 mRNA expression in the LaWaDa line was intermediate to the La and LbWbDb lines. Furthermore, principal component analysis for immune traits and MPS lesions was executed to clarify the characteristics of each pig line. These findings suggest that the immune responses in the three pig lines are genetically distinct and that MPS resistance and some immunity characteristics from the La line were transmitted to the three-way crossbred pigs.

Prenatal diagnosis of Gaucher disease using next-generation sequencing.

In the prenatal diagnosis of Gaucher disease (GD), glucocerebrosidase (GBA) activity is measured with fetal cells, and gene analysis is performed when pathogenic mutations in GBA are identified in advance. Herein is described prenatal diagnosis in a family in which two children had GD. Although prior genetic information for this GD family was not obtained, next-generation sequencing (NGS) was carried out for this family because immediate prenatal diagnosis was necessary. Three mutations were identified in this GD family. The father had one mutation in intron 3 (IVS2 + 1), the mother had two mutations in exons 3 (I[-20]V) and 5 (M85T), and child 1 had all three of these mutations; child 3 had none of these mutations. On NGS the present fetus (child 3) was not a carrier of GD-related mutations. NGS may facilitate early detection and treatment before disease onset.

[Hashimoto's encephalopathy presenting with vertigo and muscle weakness in a male pediatric patient].

Hashimoto's encephalopathy is an anti-thyroid antibody-positive autoimmune encephalopathy. We herein report the case of a 13-year-old male patient with subacute vertigo, muscle weakness in the extremities and gait disturbance who was diagnosed with Hashimoto's encephalopathy. He showed no severe impairment of consciousness and no seizures, and there were no abnormalities on the brain MRI. However, epileptic spike and wave complexes were observed on an electroencephalogram, and a decline in blood flow was diffusely observed on brain SPECT (single photon emission computed tomography). His thyroid function was normal, but he was positive for anti-thyroid antibodies, such as anti-TPO (thyroid peroxidase) antibodies. He was also positive for serum anti-NAE (NH2-terminal alpha-enolase) antibodies. Systemic corticosteroid therapy and high-dose intravenous immunoglobulin therapy were effective, greatly improving his quality of life.

Immunogenic properties and mycoplasmal pneumonia of swine (MPS) lung lesions in Large White pigs selected for higher peripheral blood immune capacity.

Immunogenic properties and mycoplasmal pneumonia of swine (MPS) lung lesions were compared between the immunity-selected Large White line and the non-selected Large White line. The selected Large White line showed a higher level of pulmonary MPS lesions compared with the non-selected Large White line. Subsequent to vaccination, the percentage of natural killer cells and T cells (CD3(+) CD4(+) CD8(-) and CD3(+) CD4(-) CD8(+) T cells) were significantly increased in the non-selected line but remained unchanged in the immunity-selected Large White line. Secretion of Mycoplasma hyopneumoniae vaccine-specific immunoblogulin G and phagocyte activity in peripheral blood were significantly higher in the immunity-selected Large White line than in the non-selected line. Expression of interleukin (IL)-4 and IL-6 messenger RNA in hilar lymph nodes was significantly lower in the immunity-selected Large White line than in the non-selected line. However, expression of IL-10 in all immune tissues was significantly higher in the immunity-selected Large White line. These results suggest that the selection for high immunity was not effective in increasing resistance to MPS lung lesions.

Immunogenic properties of Landrace pigs selected for resistance to mycoplasma pneumonia of swine.

Mycoplasma pneumonia of swine (MPS) lung lesions and immunogenic properties were compared between a Landrace line that was genetically selected for reduced incidence of pulmonary MPS lesions, and a non-selected Landrace line. The MPS-selected Landrace line showed significantly lower degrees of pulmonary MPS lesions compared with the non-selected Landrace line. When changes in immunity before and after vaccination were compared, the percentage of B cells in the peripheral blood of the MPS-selected Landrace line was significantly lower than that of the non-selected line. Furthermore, the concentration of growth hormone and the mitogen activity of peripheral blood mononuclear cells in the MPS-selected Landrace line showed significantly (P < 0.05) lower increases after vaccination than the non-selected line. Conversely, the concentration of peripheral blood interferon (IFN)-γ and salivary immunoglobulin A (IgA) after Mycoplasma hyopneumoniae vaccination was significantly higher in the MPS-selected Landrace line than in the non-selected line. Gene expression of toll-like receptor (TLR)2 and TLR4 was significantly higher in the MPS-selected Landrace line in immune tissues, with the exception of the hilar lymph nodes. The present results suggest that peripheral blood IFN-γ, salivary IgA TLR2, and TLR4 are important immunological factors influencing the development of MPS lesions.

Mycoplasma pneumonia of swine (MPS) resistance and immune characteristics of pig lines generated by crossing an MPS pulmonary lesion selected Landrace line and a highly immune capacity selected Large White line.

To understand the influence of crossbreeding on Mycoplasma pneumonia of swine (MPS) resistance and immune characteristics, two crossbred lines were characterized. One crossbred line, LaWa, was generated by crossing the MPS pulmonary lesion selected Landrace line (La) and the highly immune-selected Large White line (Wa). The second crossbred line, LaWb, was generated by crossing the La line and the nonselected Large White line (Wb). The crossbred LbWb line (nonselected Landrace line × nonselected Large White line) and the La line were used as controls. The LaWa and LaWb lines had an intermediate level of MPS lung lesions between La and LbWb lines, although the difference was not statistically significant. After stimulation with sheep red blood cells (SRBCs), the LaWb and LaWa lines showed immune characteristics similar to that of the La line; the number of monocytes in peripheral blood increased, while B cells, T cells, secretion of SRBC-specific immunoglobulin G, and interleukin (IL)-13 decreased. Additionally, the number of natural killer (NK) cells and the expression of IL-4 and IL-17 were significantly higher in the LaWb and LaWa lines, respectively. These data suggested that crossbreeding of La and Wa lines resulted in the inheritance of some of the selected immune responses.

Selection for high and low oxygen consumption altered hepatic mitochondrial energy efficiency in mice.

Selection for high (H) and low (L) oxygen consumption (OC) as an indirect estimation of maintenance energy requirement was determined. Feed intake and body weight were measured and feed conversion ratio (FCR) of 4-8-week-old mice was calculated. Respiratory activity of hepatic mitochondria was measured at 12 weeks. Total feed intake (H: 103.74 g, L: 97.92 g, P < 0.01), daily feed intake (H: 3.70 g/day, L: 3.50 g/day, P < 0.01) and FCR (H: 18.79, L: 15.50, P < 0.01) were significantly different between lines. The line by sex interaction was significant for FCR. No line differences were observed in males; and the FCR of the H line was greater than in the L line in females. H line mice had the highest hepatic mitochondrial respiratory activity in state 2 (P < 0.01), the highest uncoupled respiratory rate of mitochondria in the presence of an uncoupling agent (P < 0.001), and the mitochondrial proton leak. The adenosine diphosphate/ O ratio was highest in the L line (P < 0.05). This suggests that the selection for high and low OC induced differences in basal mitochondrial respiration and basal metabolism, resulting in difference in FCR between H and L lines.

The toll-like receptor family protein RP105/MD1 complex is involved in the immunoregulatory effect of exopolysaccharides from Lactobacillus plantarum N14.

The radioprotective 105 (RP105)/MD1 complex is a member of the Toll-like receptor (TLR) family. It was reported that RP105/MD1 cooperates with the lipopolysaccharide (LPS) receptor TLR4/MD2 complex and plays a crucial role in the response of immune cells to LPS. This work evaluated whether RP105, TLR4 or TLR2 were involved in the immunoregulatory capacities of Lactobacillus plantarum N14 (LP14) or its exopolysaccharides (EPS). EPS from LP14 were fractionated into neutral (NPS) and acidic (APS) EPS by anion exchange chromatography. Experiments with transfectant HEK(RP105/MD1) and HEK(TLR2) cells demonstrated that LP14 strongly activated NF-κB via RP105 and TLR2. When we studied the capacity of APS to activate NF-κB pathway in HEK(RP105/MD1) and HEK(TLR4) cells; we observed that APS strongly stimulated both transfectant cells. Our results also showed that LP14 and APS were able to decrease the production of pro-inflammatory cytokines (IL-6, IL-8 and MCP-1) in porcine intestinal epithelial (PIE) cells in response to enterotoxigenic Escherichia coli (ETEC) challenge. In order to confirm the role of TLR2, TLR4 and RP105 in the immunoregulatory effect of APS from LP14, we used small interfering RNA (siRNA) to knockdown these receptors in PIE cells. The capacity of LP14 and APS to modulate pro-inflammatory cytokine expression was significantly reduced in PIE(RP105-/-) cells. It was also shown that LP14 and APS were capable of upregulating negative regulators of the TLR signaling in PIE cells. This work describes for the first time that a Lactobacillus strain and its EPS reduce inflammation in intestinal epithelial cells in a RP105/MD1-dependend manner.