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Probiotics are microorganisms that confer health benefits to host. Well-known examples include Bifidobacterium and Lactobacillus species. In recent years, interest in promoting our health with probiotics has grown as life expectancy and health awareness has increased. However, some concerns for safety and stability exist for these live organisms. Thus, “postbiotics” and “paraprobiotics,” non-viable heat-killed microbial cells or cell fractions that retain health benefits, are increasingly favored. Unfortunately, little information on clinical efficacy and mechanisms of action is available compared with many available probiotics. Lacticaseibacillus (previous name Lactobacillus) paracasei MCC1849 is a commonly used lactic acid bacterial strain in Japan that displays immuno-modulatory effects in humans in non-viable heat-killed form. This review discusses health benefits of heat-killed L. paracasei MCC1849 immune modulation and offers a theoretical basis for its mechanisms of action. We also discuss the feasibility of using heat-killed probiotics for application in food products.

Antigen-specific immunoglobulin (Ig) A plays a major role in host defense against infections in gut mucosal tissue. Follicular helper T (Tfh) cells are located in germinal centers and promote IgA production via interactions with germinal center B cells. Several studies have demonstrated that some lactic acid bacteria (LAB) strains activate the host's acquired immune system, inducing IgA secretion in the intestine. However, the precise molecular mechanisms underlying the effects of LAB on IgA production and Tfh cells are not fully resolved. Lactobacillus paracasei MCC1849 is a probiotic strain isolated from the intestine of a healthy adult. In this study, we investigated the effects of orally administered heat-killed MCC1849 on IgA production in the intestine and on Tfh cell induction in vivo. We found that orally administered MCC1849 induced antigen-specific IgA production in the small intestine, serum and lungs. We also observed that MCC1849 increased the proportion of IgA+ B cells and Tfh cells in Peyer's patches (PPs). In addition, MCC1849 increased the gene expression of IL-12p40, IL-10, IL-21, STAT4 and Bcl-6 associated with Tfh cell differentiation. These results suggest that orally administered MCC1849 enhances antigen-specific IgA production and likely affects Tfh cell differentiation in PPs.

Probiotics intervention has been proposed as a feasible preventative approach against adverse health-related complications in infants. Nevertheless, the umbrella concept of probiotics has led to a massive application of probiotics in a range of products for promoting infant health, for which the strain-specificity, safety and efficacy findings associated with a specific probiotics strain are not clearly defined. Bifidobacterium breve M-16V is a commonly used probiotic strain in infants. M-16V has been demonstrated to offer potential in protecting infants from developing the devastating necrotising enterocolitis (NEC) and allergic diseases. This review comprehends the potential beneficial effects of M-16V on infant health particularly in the prevention and treatment of premature birth complications and immune-mediated disorders in infants. Mechanistic studies supporting the use of M-16V implicated that M-16V is capable of promoting early gut microbial colonisation and may be involved in the regulation of immune balance and inflammatory response to protect high-risk infants from NEC and allergies. Summarised information on M-16V has provided conceptual proof of the use of M-16V as a potential probiotics candidate aimed at promoting infant health, particularly in the vulnerable preterm population.

The interaction between the gut microbiota and the host can influence the host’s immune system. Bifidobacterium, a commensal genus of gut bacteria, seems to have positive effects on host health. Our previous clinical research showed that B. longum subsp. longum BB536 enhanced innate and adaptive immune responses in elderly individuals with a lower grade of immunity, but the immunomodulatory mechanism is still unclear. In this study, dendritic cell (DC) surface markers in peripheral blood mononuclear cells isolated from healthy individuals were evaluated through coculture with heat-killed BB536. DC markers, innate immune activity and cytokine levels in plasma were also evaluated by a randomized, double-blind, placebo-controlled, parallel-group study (UMIN000045564) with 4 weeks of continuous live BB536 intake. BB536 significantly increased the expression of CD86 and HLA-DR on plasmacytoid DCs (pDCs) in vitro. Compared to placebo (n = 48), a significant increase in the expression of CD86 on peripheral pDCs was detected at week 4 of live BB536 intake (n = 49; 1 × 1010 CFU/day). Furthermore, coculture with hk-BB536 significantly increased the IFNγ expression level and demonstrated trends of increased IFNα1 and IFNβ expression. These findings suggest that consumption of BB536 has potential immunomodulatory effects on healthy individuals through the activation of peripheral pDCs.

We previously reported that the intake of heat-killed Lacticaseibacillus paracasei MCC1849 suppressed the onset of cold-like symptoms in healthy young women who were susceptible to colds. This study aimed to investigate the effects of MCC1849 on subjective symptoms of physical condition in healthy adults of a wide age range. In this randomized, double-blind, placebo-controlled, parallel-group study, 200 healthy adults were randomly divided into the MCC1849 group or placebo group. The participants received test powder with 50 billion MCC1849 cells or placebo powder without MCC1849 for 24 weeks. Subjective symptoms were assessed by diary scores. Analysis was performed on 183 participants (MCC1849 group; n = 91, placebo group; n = 92) in the per-protocol set. The number of days of stuffy nose and cold-like symptoms was significantly reduced in the MCC1849 group compared with the placebo group. In addition, the duration of stuffy nose, sore throat and cold-like symptoms was significantly lower in the MCC1849 group. No side effects were observed. Therefore, oral intake of MCC1849 suppressed subjective symptoms in healthy adults of a wide age range. These data suggest that MCC1849 may help maintain physical condition.

In this work, we aimed to characterize the antiviral response of an originally established porcine intestinal epithelial cell line (PIE cells) by evaluating the molecular innate immune response to rotavirus (RVs). In addition, we aimed to select immunomodulatory bacteria with antiviral capabilities. PIE cells were inoculated with RVs isolated from different host species and the infective titers and the molecular innate immune response were evaluated. In addition, the protection against RVs infection and the modulation of immune response by different lactic acid bacteria (LAB) strains was studied. The RVs strains OSU (porcine) and UK (bovine) effectively infected PIE cells. Our results also showed that RVs infection in PIE cells triggered TLR3-, RIG-I- and MDA-5-mediated immune responses with activation of IRF3 and NF-κB, induction of IFN-β and up-regulation of the interferon stimulated genes MxA and RNase L. Among the LAB strains tested, Bifidobacterium infantis MCC12 and B. breve MCC1274 significantly reduced RVs titers in infected PIE cells. The beneficial effects of both bifidobacteria were associated with reduction of A20 expression, and improvements of IRF-3 activation, IFN-β production, and MxA and RNase L expressions. These results indicate the value of PIE cells for studying RVs molecular innate immune response in pigs and for the selection of beneficial bacteria with antiviral capabilities.

Bifidobacterium breve M-16V is a probiotic bacterial strain with efficacy in infants achieved by suppressing T-helper type (Th) 2 immune responses and modulating the systemic Th1/Th2 balance. Exposure to air pollution during pregnancy increases asthma susceptibility in offspring. The aim of this study was to investigate the effects of the maternal intake of B. breve M-16V on susceptibility to asthma accelerated by prenatal exposure to air pollution. The intake of B. breve M-16V in residual oil fly ash (ROFA)-exposed pregnant mice resulted in fewer eosinophils in the bronchoalveolar lavage fluid of neonatal mice and reduced allergic lung inflammation. The expressions of Th2 cytokines including IL-5 and IL-13 were decreased in neonatal mice from ROFA-exposed mothers fed B. breve M-16V. The analysis of fecal microbiota from neonatal mice revealed that the intake of B. breve M-16V by mothers changed the composition of fecal microbiota in neonatal mice, which resulted in a decreased population of Firmicutes. Moreover, several bacterial strains of fecal microbiota from neonatal mice had a strong correlation with Th2 cytokines and histological score. These results suggest that the maternal intake of M-16V might have beneficial effects in neonates by preventing and/or alleviating allergic reactions accelerated by prenatal exposure to air pollution.

Background/Objectives: Sarcopenia (SA), an age-related impairment in skeletal muscle mass and function, is related to gut microbiota (GM) through inflammation and short-chain fatty acid (SCFA) generation. However, data on this relationship in older Japanese adults remain limited. We investigated the relationship of GM composition with SA, based on the Asian Working Group for Sarcopenia (AWGS) 2019 criteria, among elderly Japanese outpatients. Methods: Between June 2022 and January 2023, this prospective cross-sectional study enrolled 356 community-dwelling outpatients aged ≥ 65 years at the Department of Gastroenterology, Juntendo Tokyo Koto Geriatric Medical Center. SA was determined based on the AWGS 2019 consensus criteria. GM was analyzed using 16S rRNA gene sequencing, and alpha/beta diversity, taxonomic composition, detection rates, and correlations with skeletal muscle mass index (SMI), grip strength, and gait speed were investigated. Results: Among 356 (144 males, 212 females) participants, 50 (35 males, 15 females) had SA. Differences in GM diversity and composition were primarily noted among male participants. Men with SA had lower alpha diversity and distinct beta diversity profiles. Six bacterial genera—Eubacterium I, Fusicatenibacter, Holdemanella, Unclassified Lachnospira, Enterococcus H, and Bariatricus—had lower abundances in the SA group. Several of these genera showed positive correlations with SMI, grip strength, and gait speed. Conversely, no differences in GM characteristics were seen among females. Conclusions: GM composition was associated with SA among older Japanese men. These sex-specific differences emerged consistently, highlighting the potential of microbiota-based strategies for SA prevention in older males.

Background: Oral probiotic intake is suggested to have positive effects on skin. We aimed to elucidate the effects of oral Bifidobacterium breve M-16V intake on skin by analyzing facial images, the skin myco/microbiota, and the gut microbiota. Methods: We conducted a randomized, double-blind, placebo-controlled study in Japan. Healthy women aged over 30 years were randomly allocated to either the B. breve (1 × 1010 colony-forming units (CFU)/sachet, two sachets daily) or the placebo group and consumed the corresponding study food for 12 weeks. Facial images were taken at weeks 0, 4, 8, and 12 using VISIA evolution. Stool and skin samples were collected at weeks 0 and 12. The primary outcome was the change in the total VISIA score from baseline. Results: A total of 120 females aged 30–79 years were assigned to the B. breve (n = 59) or placebo (n = 61) group. The total VISIA score worsened in the placebo group at week 8 (p = 0.029) but not in the B. breve group. Compared with that of the placebo group, the VISIA brown spot score of the B. breve group improved at weeks 4 (p = 0.013) and 8 (p = 0.041). The VISIA pore score improved at weeks 4 (p = 0.013), 8 (p = 0.041), and 12 (p = 0.004) within the B. breve group. Genus-level analysis of the gut microbiota revealed a significant increase in Blautia abundance in the B. breve group. The frequency of adverse events was not different between the groups. Conclusions: Oral B. breve M-16V administration may suppress skin deterioration, including the appearance of brown spots, on the faces of adult females.

We previously showed that evaluation of anti-inflammatory activities of lactic acid bacteria in porcine intestinal epithelial (PIE) cells is useful for selecting potentially immunobiotic strains. The aims of the present study were: i) to select potentially immunomodulatory bifidobacteria that beneficially modulate the Toll-like receptor (TLR)-4-triggered inflammatory response in PIE cells and; ii) to gain insight into the molecular mechanisms involved in the anti-inflammatory effect of immunobiotics by evaluating the role of TLR2 and TLR negative regulators in the modulation of proinflammatory cytokine production and activation of mitogen-activated protein kinase (MAPK) and nuclear factor-κB (NF-κB) pathways in PIE cells. Bifidobacteria longum BB536 and B. breve M-16V strains significantly downregulated levels of interleukin (IL)-8, monocyte chemotactic protein (MCP)-1 and IL-6 in PIE cells challenged with heat-killed enterotoxigenic Escherichia coli. Moreover, BB536 and M-16V strains attenuated the proinflammatory response by modulating the NF-κB and MAPK pathways. In addition, our findings provide evidence for a key role for the ubiquitin-editing enzyme A20 in the anti-inflammatory effect of immunobiotic bifidobacteria in PIE cells. We show new data regarding the mechanism involved in the anti-inflammatory effect of immunobiotics. Several strains with immunoregulatory capabilities used a common mechanism to induce tolerance in PIE cells. Immunoregulatory strains interacted with TLR2, upregulated the expression of A20 in PIE cells, and beneficially modulated the subsequent TLR4 activation by reducing the activation of MAPK and NF-κB pathways and the production of proinflammatory cytokines. We also show that the combination of TLR2 activation and A20 induction can be used as biomarkers to screen and select potential immunoregulatory bifidobacteria strains.