Articles

Bifidobacteria and Intestinal Flora

Title	Comprehensive analysis of metabolites produced by co-cultivation of Bifidobacterium breve MCC1274 with human iPS-derived intestinal epithelial cells
Author	A.Sen, T.Nishimura, S.Yoshimoto, K.Yoshida, A.Gotoh1, T.Katoh1, Y.Yoneda2, T.Hashimoto2, JZ.Xiao, T.Katayama1, and T.Odamaki 1Division of Integrated Life Science, Graduate School of Biostudies, Kyoto University, *2Technology Research Laboratory, Shimadzu Corp.
Journal	Frontiers in microbiology 14:1155438 (2023)
Summary	We evaluated the metabolic interaction betwenn Bifidobacterium breve MCC1274 and iPS-derived intestinal epithelial cells using a novel coculture device. We observed a significant increase in the amount of the immunomodulatory metabolites indole-3-lactic acid and phenyllactic acid in the co-culture.

Title	Early probiotic supplementation of healthy term infants with Bifidobacterium longum subsp. Infantis M-63 is safe and leads to the development of Bifidobacterium-predominant gut microbiota: A double-blind, placebo-controlled trial
Author	A.Hiraku, S.Nakata1, M.Murata, C.Xu, N.Mutoh, S.Arai, T.Odamaki, N.Iwabuchi, M.Tanaka, T.Tsuno1, and M.Nakamura2 1Department of Pediatrics, Matsumoto City Hospital, *2Department of neurosurgery, Matsumoto City Hospital
Journal	Nutrients 15(6):1402(2023)
Summary	In this study, healthy term infants were given Bifidobacterium longum subsp. infantis (B. infantis) M-63 (1 × 10^9 CFU/day) or placebo from postnatal age ≤ 7 days to 3 months. Supplementation with B. infantis M-63 significantly increased the relative abundance of Bifidobacterium in the gut microbiota and the amount of acetic acid and IgA in the stool, compared with the placebo group. No adverse events related to test foods were observed.

Title	Effects of heat-killed Lacticaseibacillus paracasei MCC1849 on the maintenance of physical condition in healthy adults: A randomized, double-blind, placebo-controlled, parallel-group study
Author	S.Sato, S.Arai, N.Iwabuchi, M.Tanaka, R.Hase1, and N.Sakane2 1Department of Public Health and Preventive Medicine, Yamaguchi University Graduate School of Medicine, 2Division of Preventive Medicine, Clinical Research Institute, National Hospital Organization Kyoto Medical Center
Journal	Nutrients 15(15):3450 (2023)
Summary	In a clinical study of healthy adults, the intake of 50 billion cells of heat-killed Lacticaseibacillus paracasei MCC1849 (LAC-Shield™) significantly reduced the number of days and durations of ”nasal congestion" and ”cold-like symptoms”, and the duration of ”sore throat". These results suggest that MCC1849 may help maintain physical condition in healthy adults

Title	Heat-killed L. helveticus enhances positive mood states: A randomized, double-blind, placebo-controlled study
Author	N.Mutoh, I.Kakiuchi1, K.Kato, C.Xu, N.Iwabuchi, M.Ayukawa1, K.Kiyosawa2, K.Igarashi1, M.Tanaka, M.Nakamura3, and M.Miyasaka2 1Faculty of Nursing, Matsumoto College of Nursing, 2Department of Nursing, Matsumoto Junior College, *3Matsumoto City Hospital
Journal	Brain Sciences 13(6): 973 (2023)
Summary	Healthy nursing students were administered heat-killed Lactobacillus helveticus MCC1848 at 5 billion/day for 4 weeks to investigate the efficacy on positive and negative mood. In the MCC1848 group, there was a significant improvement in positive mood on the questionnaire items, suggesting that heat-killed MCC1848 is effective in enhancing positive mood.

Title	Heat-killed Lactobacillus helveticus improves mood states: a randomised, double-blind, placebo-controlled study
Author	N.Mutoh, I.Kakiuchi1, A.Hiraku, N.Iwabuchi, K.Kiyosawa1, K.Igarashi1, M.Tanaka, M.Nakamura2, and M.Miyasaka1 1Department of Nursing, Matsumoto Junior College, *2Matsumoto City Hospital
Journal	Beneficial Microbes 14(2): 109-117 (2023)
Summary	Healthy young adults were administrated heat-killed Lactobacillus helveticus MCC1848 at 5 billion/day for 4 weeks to investigate the effects on daily mood state. Two measures of positive mood state, the "friendliness" score and the "relaxed" score, were significantly improved in the MCC1848 group, suggesting that heat-killed MCC1848 may improve positive mood state.

Title	Studies on the Physiological Functions of Bifidobacteria and Lactic Acid bacteria as well as Their Industrial Applications(Award Review)
Author	K. Shimizu (Jz. Xiao)
Journal	Japanese Journal of Lactic Acid Bacteria 33(3): 155-168 (2022)
Summary	In this review, we will discuss (1) results obtained by addressing the proposition of "why bifidobacteria live in the human abdomen and what they do there," (2) the development of a mixed fermentation method with Lactococcus lactis, which enabled the production of fermented milk containing high bacteria count and high survival rate of bifidobacteria, and (3) the studies on the effect of Bifidobacterium breve MCC1274 on cognitive function and its mechanism of action, focusing on the "gut-brain axis". The author reviewed the contents related to the basic, functional, and applied research on bifidobacteria, tracing the path of research and development he has been involved.

Title	Synbiotics of Bifidobacterium breve MCC1274 and lactulose enhances production of tryptophan metabolites in fermented human fecal communities.
Author	N.Hashikura, R.Murakami, T.Sakurai, A.Horigome, K.Toda, JZ.Xiao, and T.Odamaki
Journal	Food Research International 163: 112308 (2023)
Summary	We evaluated the effects of Bifidobacterium MCC1274 and lactulose on the gut environment using an artificial gut model. The combination of these two components, known as synbiotics, markedly increased the production of tryptophan metabolites, which serve as signaling molecules.

Title	Fermentation supernatant of elderly feces with inulin and partially hydrolyzed guar gum maintains the barrier of inflammation-induced Caco-2/HT29-MTX-E12 co-cultured cells
Author	G.Kono, K.Yoshida, E.Kokubo, M.Ikeda, T.Matsubara, T.Koyama*, H.Iwamoto, and K.Miyaji
Journal	Journal of Agricultural and Food Chemistry 71(3): 1510-1517 (2023)
Summary	We evaluated the effect of dietary fibers and indigestible oligosaccharides on intestinal barrier function by altering the microbiota of the elderly. The results indicated inulin and partially hydrolyzed guar gum can change the intestinal environment of the elderly and maintain the intestinal barrier by accelerating the production of short-chain fatty acids and modifying the expression levels of barrier function-related genes.

Title	Cross-feeding among bifidobacteria on glycomacropeptide
Author	M.Morozumi, Y.Wada, M.Tsuda, F.Tabata, T.Ehara, H.Nakamura, and K.Miyaji
Journal	Journal of Functional Foods 103: 105463 (2023)
Summary	Bifidobacteria are considered beneficial for infant health, however, they are less prevalent in gut microbiota of formula-fed than in breast-fed infants. This study investigated the bifidogenic effects of cow’s glycomacropeptide (GMP) and metabolic enzymes that Bifidobacterium bifidum JCM1254 uses when grown in the GMP-containing medium. GMP glycans are “cross-fed” among bifidobacteria, and carbohydrate metabolism-related proteins, expressed by Bifidobacterium bifidum, is involved in the cross-feeding.

Title	Probiotic Bifidobacterium breve MCC1274 protects against oxidative stress and neuronal lipid droplet formation via PLIN4 gene regulation
Author	F.Bernier, T.Kuhara, and Jz.Xiao
Journal	Microorganisms 11(3), 791 (2023)
Summary	Consumption of Bifidobacterium breve MCC1274 has been shown to improve memory and prevent brain atrophy in populations with mild cognitive impairment (MCI). In this study, we found that B. breve MCC1274 cell extracts significantly decreased the expression of perilipin 4 (PLIN4), which encodes a lipid droplet docking protein whose expression is known to be increased during inflammation in SH-SY5Y cells. Niacin, an MCC1274 cell extract component, increased PLIN4 expression by itself. Moreover, MCC1274 cell extracts and niacin blocked the PLIN4 induction caused by oxidative stress in SH-SY5Y cells, reduced lipid droplet formation, and prevented IL-6 cytokine production. These results offer a possible explanation for the effect of this strain on brain inflammation.

Title	2'-fucosyllactose increases the abundance of Blautia in the presence of extracellular fucosidase-possessing bacteria
Author	A.Horigome, N.Hashikura, K.Yoshida, JZ.Xiao, and T.Odamaki
Journal	Frontiers in Microbiology 13:913624 (2022)
Summary	We have previously shown that 2'-fucosyllactose (2'-FL), a major component of human milk oligosaccharides, increases the relative abundance of Blautia sp., which is one of the bacterial taxa that declines with age, in the cultured fecal microbiota of healthy adults. In this study, we revealed that the presence of extracellular fucosidase-possessing gut bacteria is key for the increase of Blautia sp. by 2'-FL.

Title	Effects of Bifidobacterium breve A1 on the cognitive function of older adults with memory complaints: a randomised, double-blind, placebo-controlled trial.
Author	Y.Kobayashi, T.Kuhara, M.Oki, and Jz.Xiao Seishukai Clinic
Journal	Beneficial Microbes 10(5):511-520 (2019)
Summary	Intakes of B. breve A1 for 12 weeks showed a significant improvement in the immediate memory function and MMSE score compared to the placebo group in elderly people with low cognitive function index.

Title	Neonatal oral fluid as a transmission route for bifidobacteria to the infant gut immediately after birth.
Author	K.Toda, K.Hisata1, T.Satoh2, N.Katsumata, T.Odamaki, E.Mitsuyama, T.Katayama3, T.Kuhara, K.Aisaka4, T.Shimizu1, and Jz.Xiao 1Department of Pediatrics and Adolescent Medicine, Juntendo University Graduate School of Medicine, 2Department of Molecular Microbiology, Tokyo University of Agriculture, 3Division of Integrated Life Science, Graduate School of Biostudies, Kyoto University, *4Department of Obstetrics and Gynecology, Hamada Hospital
Journal	Scientific Reports 9(1):8692 (2019)
Summary	We found viable Bifidobacterium in neonatal oral fluid just after birth, and some of them were detected in corresponding infant feces at one month after birth. These results suggest that Bifidobacterium can be transmitted to neonatal oral fluid just after birth, followed by colonizing infant gut.

Title	Impact of a bathing tradition on shared gut microbe among Japanese families
Author	T.Odamaki, F.Bottacini, E.Mitsuyama, K.Yoshida, K.Kato, JZ.Xiao, and D.van Sinderen *APC Microbiome Ireland and School of Microbiology, National University of Ireland
Journal	Scientific Reports 9(1): Art.No. 4380 (2019)
Summary	Sharing of Bifidobacterium longum strains had recently been shown to occur among Japanese family members, a phenomenon that is not confined to mother-infant pairs. In the current study, we investigated if bathtub water is a possible vehicle for the exchange of strains as a consequence of a Japanese custom to share bathtub water by family members during bathing practices. Viable bifidobacterial strains were isolated from all bathtub water samples. We showed that the fecal microbiota composition among family members that share bathtub water is significantly closer than that between family members that do not engage in this practice. Our results indicate that bathtub water represents a vehicle for the transmission of gut bacteria, and that the Japanese custom of sharing bathtub water contributes to the exchange of gut microbes, in particular bifidobacteria, among family members.

Title	Bifidobacterium breve A1 supplementation improved cognitive decline in older adults with mild cognitive impairment: an open-label, single-arm study
Author	Y.Kobayashi, T.Kinoshita1, A.Matsumoto2, K.Yoshino2, I.Saito1, and JZ.Xiao 1Ehime Univ. 2Aki Orthopedic Rehabilitation Clinic
Journal	The Journal of Prevention of Alzheimer's Disease 6(1):70-75 (2019)
Summary	We conducted an open-label, single-arm study to examine the effects of 24-week supplementation of B. breve A1 on 19 elderly with mild cognitive impairment(MCI). The study showed that oral supplementation of B. breve A1 in participants with MCI improved cognitive function.

Title	Association between functional lactase variants and a high abundance of Bifidobacterium in the gut of healthy Japanese people
Author	K.Kato, S.Ishida, M.Tanaka, E.Matsuyama, Jz.Xiao, and T.Odamaki 1Business Planning Group, Next Generation Science Institute, DeNA Life Science, Inc., 2RandD Group, DeNA Life Science, Inc.
Journal	PLoS ONE　13(10), e0206189(2018)
Summary	We investigated the possible contribution of functional lactase loci to the high abundance of Bifidobacterium in Japanese populations. The results indicated low lactase activity in Japanese people and possible contribution of host genetic variation-associated low lactase activity to the high abundance of Bifidobacterium in the Japanese population.

Title	Breast milk on the infant faecal microbiome: Components of breast milk orchestrating the establishment of bifidobacteria species.
Author	C.B.Wong and Jz.Xiao
Journal	Journal of Human Nutrition & Food Science 6(2): 1123 (2018)
Summary	In this review, we introduced the reason why only human bifidobacteria proliferate in the intestine of babies, focusing on their compatibility with oligosaccharides and lysozyme in breast milk.

Title	Effects of paraprobiotic Lactobacillus paracasei MCC1849 supplementation on symptoms of the common cold and mood states in healthy adults
Author	M.Murata, J.Kondo1, N.Iwabuchi, S.Takahashi, K.Yamauchi, F.Abe, and K.Miura2 1 Department of Food and Nutrition, Higashi Chikushi Junior College, 2 Department of Nutrition, Faculty of Home Economics, Kyushu Women’s University
Journal	Beneficial Microbes 9 (6): 855-864 (2018)
Summary	The effects of heat-killed Lactobacillus paracasei MCC1849 (LAC-Shield™) on the common cold and mood states during winter in healthy adults were evaluated in a randomised, double-blind, placebo-controlled trial. In a subgroup of subjects susceptible to the common cold, the incidence and symptom scores of the common cold significantly improved in the 10 billion cell MCC1849-intake group. The results of this study indicate that paraprobiotic L. paracasei MCC1849 has the potential to improve resistance to common cold infections and maintain a desirable mood state, even under mental stress conditions.

Title	Effects of Bifidobacterium breve B-3 on body fat reductions in pre-obese adults: A randomized, double-blind, placebo-controlled trial
Author	J.Minami, N.Iwabuchi, M.Tanaka, K.Yamauchi, J.Xiao, F.Abe, and N.Sakane* *National Hospital Organization Kyoto Medical Center
Journal	Bioscience of Microbiota, Food and Health 37(3): 67-75(2018)
Summary	The effects of the consumption of Bifidobacterium breve B-3 on body fat reduction in healthy pre-obese (25 ≤ BMI < 30) adults were investigated in a double-blind, placebo-controlled trial. Body fat mass was significantly lower in the B-3 group than in the placebo group. Waist circumference in the B-3 group was significantly lower at week 12 than at the baseline.

Title	Genomic diversity and distribution of Bifidobacterium longum subsp. longum across the human lifespan
Author	T.Odamaki, F.Bottacini, K.Kato, E.Mitsuyama, K.Yoshida, A.Horigome, JZ.Xiao, and D.van Sinderen *APC Microbiome Institute and School of Microbiology, National University of Ireland
Journal	Scientific Reports 8(1): Art. 85 (2018)
Summary	We performed a comparative genome analysis of Bifidobacterium longum subsp. longum to unravel the reason why this subspecies are widely distributed across all generation. As results, a broad distribution of them across the human lifespan is due to a high transfer level between family members. We furthermore identified a variety of genes which could enhance their adaptation and increase competitiveness in the gut environment, enriched in genomes corresponding to specific ages.