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Bifidobacterium longum

From Wikipedia, the free encyclopedia

Bifidobacterium longum
Scientific classification Edit this classification
Domain: Bacteria
Kingdom: Bacillati
Phylum: Actinomycetota
Class: Actinomycetes
Order: Bifidobacteriales
Family: Bifidobacteriaceae
Genus: Bifidobacterium
Species:
B. longum
Binomial name
Bifidobacterium longum
Reuter 1963 (Approved Lists 1980)[1]
Representative morphologic characteristics of B. longum subsp. longum strains

Bifidobacterium longum is a Gram-positive, catalase-negative, rod-shaped bacterium present in the human gastrointestinal tract and one of the 32 species that belong to the genus Bifidobacterium.[2][3] It is a microaerotolerant anaerobe and considered to be one of the earliest colonizers of the gastrointestinal tract of infants.[2] When grown on general anaerobic medium, B. longum forms white, glossy colonies with a convex shape.[4] B. longum is one of the most common bifidobacteria present in the gastrointestinal tracts of both children and adults.[5] B. longum is non-pathogenic, is often added to food products,[2][6] and its production of lactic acid is believed to prevent growth of pathogenic organisms.[7]

Classification

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In 2002, three previously distinct species of Bifidobacterium, B. infantis, B. longum, and B. suis, were unified into a single species named B. longum with the biotypes infantis, longum, and suis, respectively.[8] This occurred as the three species had extensive DNA similarity including a 16S rRNA gene sequence similarity greater than 97%.[9] In addition, the three original species were phenotypically difficult to distinguish due to different carbohydrate fermentation patterns among strains of the same species.[2] As probiotic activity varies among strains of B. longum, interest exists in the exact classification of new strains, although this is made difficult by the high gene similarity between the three biotypes.[10] Currently, strain identification is done through polymerase chain reaction (PCR) on the subtly different 16S rRNA gene sequences.[10]

Subspecies B. infantis

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Bifidobacterium longum subsp. infantis (B. infantis) exists primarily in the intestine of breast-fed infants.[11] B. infantis is unique in its ability to digest and consume human milk oligosaccharides (HMOs).[11] Unlike the other subspecies, B. infantis contains a 43-kb gene cluster, or HMO Cluster I, that encodes transport proteins and glycolyl hydrolases that allow it to transport HMOs inside the cell and break them down completely.[12]

The presence of B. infantis in the gut of infants proves to have many health benefits. It has a competitive advantage which results in less diversity in the infant gut microbiota and therefore fewer luminal pathogens. It also decreases intestinal permeability while increasing stability of tight junction proteins.[13] It promotes the maturation of the innate immune response and promotes anti-inflammatory properties.[14] Therefore, premature infants without B. infantis, have gut dysbiosis and an increased risk of necrotizing enterocolitis and late-onset sepsis. Currently, there is research on the use of probiotics with B. infantis for premature infants.[14]

Environment

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B. longum colonizes the human gastrointestinal tract, where it, along with other Bifidobacterium species, represents up to 90% of the bacteria of an infant's gastrointestinal tract.[3] This number gradually drops to 3% in an adult's gastrointestinal tract as other enteric bacteria such as Bacteroides and Eubacterium begin to dominate.[7] Some strains of B. longum were found to have high tolerance for gastric acid and bile, suggesting that these strains would be able to survive the gastrointestinal tract to colonize the lower small and large intestines.[6][15] The persistence of B. longum in the gut is attributed to the glycoprotein-binding fimbriae structures and bacterial polysaccharides, the latter of which possess strong electrostatic charges that aid in the adhesion of B. longum to intestinal endothelial cells.[2][16] This adhesion is also enhanced by the fatty acids in the lipoteichoic acid of the B. longum cell wall.[16]

Metabolism

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B. longum is considered to be a scavenger, possessing multiple catabolic pathways to use a large variety of nutrients to increase its competitiveness among the gut microbiota.[7] Up to 19 types of permease exist to transport various carbohydrates with 13 being ATP-binding cassette transporters.[17] B. longum has several glycosyl hydrolases to metabolise complex oligosaccharides for carbon and energy.[3] This is necessary as mono- and disaccharides have usually been consumed by the time they reach the lower gastrointestinal tract where B. longum resides.[2] In addition, B. longum can uniquely ferment galactomannan-rich natural gum using glucosaminidases and alpha-mannosidases that participate in the fermentation of glucosamine and mannose, respectively.[2] The high number of genes associated with oligosaccharide metabolism is a result of gene duplication and horizontal gene transfer, indicating that B. longum is under selective pressure to increase its capability to compete for various substrates in the gastrointestinal tract.[2]

Furthermore, B. longum possesses hydrolases, deaminases, and dehydratases to ferment amino acids.[2] B. longum also has bile salt hydrolases to hydrolyze bile salts into amino acids and bile acids. The function of this is not clear, although B. longum could use the amino acids products to better tolerate bile salts.[18]

Among six tested strains of Bifidobacterium from human gut, only B. longum biotype infantis demonstrated significant growth on human milk oligosaccharides as the sole carbon source.[19]

Pathogenesis

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A number of cases of B. longum infection have been reported in the scientific literature. These are primarily cases in preterm infants that are undergoing probiotic treatment,[20][21][22] although there are also reports of infection in adults.[23][24][25] Infection in preterm infants manifests as bacteremia or necrotizing enterocolitis,[26] while in adults there have been reports of sepsis and peritonitis.[23][25]

Research on beneficial properties

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Along with B. adolescentis, B. longum has been found at relatively high levels in the GI tracts of healthy humans.[27][28] Numerous strains have been described, including several whose genomes have been completely sequenced, such as B. longum subsp. longum BBMN68,[29] KACC 91563,[30] GT15,[31] NCIMB 8809,[32] W11,[33] Jih1,[34] JCM7052,[35] BCBL-583,[36] and iVE-15,[37] and B. longum subsp. infantis ATCC15697,[38] CECT 7210,[39] B2-01,[40] and YLGB-1496.[41] From animal models or clinical trials, various B. longum strains have been demonstrated to improve migraine symptoms,[42] respiratory illness,[43] pollen allergies,[44] assorted gastrointestinal issues,[45][46][47][48][49] blood sugar[50][51] and triglyceride levels,[52] cognitive parameters,[53][54][55] and immunological protection.[56][57]

See also

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References

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  1. ↑ Parte, A.C. "Bifidobacterium". LPSN.
  2. 1 2 3 4 5 6 7 8 9 Schell, M. A.; Karmirantzou, M.; Snel, B.; Vilanova, D.; Berger, B.; Pessi, G.; Zwahlen, M. -C.; Desiere, F.; Bork, P.; Delley, M.; Pridmore, R. D.; Arigoni, F. (2002). "The genome sequence of Bifidobacterium longum reflects its adaptation to the human gastrointestinal tract". Proceedings of the National Academy of Sciences. 99 (22): 14422–14427. Bibcode:2002PNAS...9914422S. doi:10.1073/pnas.212527599. PMC 137899. PMID 12381787.
  3. 1 2 3 Garrido, D.; Ruiz-Moyano, S.; Jimenez-Espinoza, R.; Eom, H. J.; Block, D. E.; Mills, D. A. (2013). "Utilization of galactooligosaccharides by Bifidobacterium longum subsp. Infantis isolates". Food Microbiology. 33 (2): 262–270. doi:10.1016/j.fm.2012.10.003. PMC 3593662. PMID 23200660.
  4. ↑ Young Park, Shin; Lee, Do Kyung; Mi An, Hyang; Gyeong Cha, Min; Baek, Eun Hae; Rae Kim, Jung; Lee, Si Won; Kim, Mi Jin; Lee, Kang Oh; Joo Ha, Nam (1 July 2011). "Phenotypic and genotypic characterization of Bifidobacterium isolates from healthy adult Koreans". Iranian Journal of Biotechnology. 9 (3): 173–180. CiteSeerX 10.1.1.833.1384. {{cite journal}}: Cite uses deprecated parameter |citeseerx= (help)
  5. ↑ Pasolli, Edoardo; Schiffer, Lucas; Manghi, Paolo; Renson, Audrey; Obenchain, Valerie; Truong, Duy Tin; Beghini, Francesco; Malik, Faizan; Ramos, Marcel; Dowd, Jennifer B; Huttenhower, Curtis; Morgan, Martin; Segata, Nicola; Waldron, Levi (November 2017). "Accessible, curated metagenomic data through ExperimentHub". Nature Methods. 14 (11): 1023–1024. doi:10.1038/nmeth.4468. PMC 5862039. PMID 29088129.
  6. 1 2 Yazawa, Kazuyuki; Fujimori, Minoru; Amano, Jun; Kano, Yasunobu; Taniguchi, Shun'ichiro (February 2000). "Bifidobacterium longum as a delivery system for cancer gene therapy: Selective localization and growth in hypoxic tumors". Cancer Gene Therapy. 7 (2): 269–274. doi:10.1038/sj.cgt.7700122. PMID 10770636. S2CID 7375660.
  7. 1 2 3 Yuan, Jing; Zhu, Li; Liu, Xiankai; Li, Ting; Zhang, Ying; Ying, Tianyi; Wang, Bin; Wang, Junjun; Dong, Hua; Feng, Erling; Li, Qiang; Wang, Jie; Wang, Hongxia; Wei, Kaihua; Zhang, Xuemin; Huang, Cuifeng; Huang, Peitang; Huang, Liuyu; Zeng, Ming; Wang, Hengliang (June 2006). "A Proteome Reference Map and Proteomic Analysis of Bifidobacterium longum NCC2705". Molecular & Cellular Proteomics. 5 (6): 1105–1118. doi:10.1074/mcp.M500410-MCP200. PMID 16549425.
  8. ↑ Sakata, Shinji; Kitahara, Maki; Sakamoto, Mitsuo; Hayashi, Hidenori; Fukuyama, Masafumi; Benno, Yoshimi (1 November 2002). "Unification of Bifidobacterium infantis and Bifidobacterium suis as Bifidobacterium longum". International Journal of Systematic and Evolutionary Microbiology. 52 (6): 1945–1951. Bibcode:2002IJSEM..52.1945S. doi:10.1099/00207713-52-6-1945. PMID 12508852.
  9. ↑ Mattarelli, P.; Bonaparte, C.; Pot, B.; Biavati, B. (1 April 2008). "Proposal to reclassify the three biotypes of Bifidobacterium longum as three subspecies: Bifidobacterium longum subsp. longum subsp. nov., Bifidobacterium longum subsp. infantis comb. nov. and Bifidobacterium longum subsp. suis comb. nov". International Journal of Systematic and Evolutionary Microbiology. 58 (4): 767–772. doi:10.1099/ijs.0.65319-0. PMID 18398167.
  10. 1 2 Šrůtková, Dagmar; Španova, Alena; Špano, Miroslav; Dráb, Vladimír; Schwarzer, Martin; Kozaková, Hana; Rittich, Bohuslav (October 2011). "Efficiency of PCR-based methods in discriminating Bifidobacterium longum ssp. longum and Bifidobacterium longum ssp. infantis strains of human origin". Journal of Microbiological Methods. 87 (1): 10–16. doi:10.1016/j.mimet.2011.06.014. PMID 21756944.
  11. 1 2 Li, Mingjie; Zhou, Xingya; Stanton, Catherine; Ross, R. Paul; Zhao, Jianxin; Zhang, Hao; Yang, Bo; Chen, Wei (Aug 11, 2021). "Comparative Genomics Analyses Reveal the Differences between B. longum subsp. infantis and B. longum subsp. longum in Carbohydrate Utilisation, CRISPR-Cas Systems and Bacteriocin Operons". Microorganisms. 9 (8): 1713. doi:10.3390/microorganisms9081713. PMC 8399906. PMID 34442792.
  12. ↑ Underwood, Mark A.; German, J. Bruce; Lebrilla, Carlito B.; Mills, David A. (Jan 14, 2015). "Bifidobacterium longum subspecies infantis: champion colonizer of the infant gut". Pediatric Research. 77 (1–2): 229–235. doi:10.1038/pr.2014.156. PMC 4350908. PMID 25303277.
  13. ↑ Chichlowski, Maciej; Shah, Neil; Wampler, Jennifer L.; Wu, Steven S.; Vanderhoof, Jon A. (May 28, 2020). "Bifidobacterium longum Subspecies infantis (B. infantis) in Pediatric Nutrition: Current State of Knowledge". Nutrients. 12 (6): 1581. doi:10.3390/nu12061581. PMC 7352178. PMID 32481558.
  14. 1 2 Batta, Vamsi K.; Rao, Shripada C.; Patole, Sanjay K. (Dec 14, 2023). "Bifidobacterium infantis as a probiotic in preterm infants: a systematic review and meta-analysis". Pediatric Research. 94 (6): 1887–1905. doi:10.1038/s41390-023-02716-w. PMC 10665187. PMID 37460707.
  15. ↑ Xiao, J.Z.; Kondo, S.; Takahashi, N.; Miyaji, K.; Oshida, K.; Hiramatsu, A.; Iwatsuki, K.; Kokubo, S.; Hosono, A. (July 2003). "Effects of Milk Products Fermented by Bifidobacterium longum on Blood Lipids in Rats and Healthy Adult Male Volunteers". Journal of Dairy Science. 86 (7): 2452–2461. doi:10.3168/jds.S0022-0302(03)73839-9. PMID 12906063.
  16. 1 2 Abbad Andaloussi, S.; Talbaoui, H.; Marczak, R.; Bonaly, R. (November 1995). "Isolation and characterization of exocellular polysaccharides produced by Bifidobacterium longum". Applied Microbiology and Biotechnology. 43 (6): 995–1000. doi:10.1007/BF00166915. PMID 8590666. S2CID 10837355.
  17. ↑ Parche, S.; Amon, J.; Jankovic, I.; Rezzonico, E.; Beleut, M.; Barutçu, H.; Schendel, I.; Eddy, M. P.; Burkovski, A.; Arigoni, F.; Titgemeyer, F. (2007). "Sugar Transport Systems of Bifidobacterium longum NCC2705". Journal of Molecular Microbiology and Biotechnology. 12 (1–2): 9–19. doi:10.1159/000096455. PMID 17183207. S2CID 21532161.
  18. ↑ Tanaka, H.; Hashiba, H.; Kok, J.; Mierau, I. (2000). "Bile salt hydrolase of Bifidobacterium longum-biochemical and genetic characterization". Applied and Environmental Microbiology. 66 (6): 2502–2512. Bibcode:2000ApEnM..66.2502T. doi:10.1128/aem.66.6.2502-2512.2000. PMC 110569. PMID 10831430.
  19. ↑ German, JB; Lebrilla, CB; Mills, DA (2012). "Human milk oligosaccharides: evolution, structures and bioselectivity as substrates for intestinal bacteria". Nestle Nutr Workshop Ser Pediatr Program. Nestlé Nutrition Workshop Series: Pediatric Program. 62: 205–22. doi:10.1159/000146322. ISBN 978-3-8055-8553-8. PMC 2861563. PMID 18626202.{{cite journal}}: CS1 maint: periodical has ISBN (link)
  20. ↑ Zbinden, Andrea; Zbinden, Reinhard; Berger, Christoph; Arlettaz, Romaine (2015). "Case Series of Bifidobacterium longum Bacteremia in Three Preterm Infants on Probiotic Therapy" (PDF). Neonatology. 107 (1): 56–59. doi:10.1159/000367985. PMID 25402825. S2CID 33816095.
  21. ↑ Esaiassen, Eirin; Cavanagh, Pauline; Hjerde, Erik; Simonsen, Gunnar S.; Støen, Ragnhild; Klingenberg, Claus (September 2016). "Subspecies Bacteremia in 3 Extremely Preterm Infants Receiving Probiotics". Emerging Infectious Diseases. 22 (9): 1664–1666. doi:10.3201/eid2209.160033. PMC 4994345. PMID 27532215.
  22. ↑ Bertelli, Claire; Pillonel, Trestan; Torregrossa, Anaïs; Prod'hom, Guy; Fischer, Céline Julie; Greub, Gilbert; Giannoni, Eric (15 March 2015). "Bifidobacterium longum Bacteremia in Preterm Infants Receiving Probiotics". Clinical Infectious Diseases. 60 (6): 924–927. doi:10.1093/cid/ciu946. PMID 25472946.
  23. 1 2 Ha, Gyoung Yim; Yang, Chang Heon; Kim, Heesoo; Chong, Yunsop (April 1999). "Case of Sepsis Caused by Bifidobacterium longum". Journal of Clinical Microbiology. 37 (4): 1227–1228. doi:10.1128/JCM.37.4.1227-1228.1999. ISSN 0095-1137. PMC 88684. PMID 10074561.
  24. ↑ Wilson, Heather L.; Ong, Chong Wei (October 2017). "Bifidobacterium longum vertebrodiscitis in a patient with cirrhosis and prostate cancer". Anaerobe. 47: 47–50. doi:10.1016/j.anaerobe.2017.04.004. PMID 28408274.
  25. 1 2 Tena, Daniel; Losa, Cristina; Medina, María José; Sáez-Nieto, Juan Antonio (June 2014). "Peritonitis caused by Bifidobacterium longum: Case report and literature review". Anaerobe. 27: 27–30. doi:10.1016/j.anaerobe.2014.03.005. PMID 24657157.
  26. ↑ Zbinden, Andrea; Zbinden, Reinhard; Berger, Christoph; Arlettaz, Romaine (2015). "Case Series of Bifidobacterium longum Bacteremia in Three Preterm Infants on Probiotic Therapy" (PDF). Neonatology. 107 (1): 56–59. doi:10.1159/000367985. PMID 25402825. S2CID 33816095.
  27. ↑ Odamaki, Toshitaka; Bottacini, Francesca; Kato, Kumiko; Mitsuyama, Eri; Yoshida, Keisuke; Horigome, Ayako; Xiao, Jin-zhong; van Sinderen, Douwe (8 January 2018). "Genomic diversity and distribution of Bifidobacterium longum subsp. longum across the human lifespan". Scientific Reports. 8 (1) 85. Bibcode:2018NatSR...8...85O. doi:10.1038/s41598-017-18391-x. PMC 5758520.
  28. ↑ Van Haute, Mallory J.; Chacón-Vargas, Katherine; Christensen, Chloe M.; Yumul, Shara R. P.; Abdulaali, Fatimah F.; Benson, Andrew K.; Hutkins, Robert; Auchtung, Thomas A. (25 November 2025). "Comparative genomic and phenotypic analysis of potential beneficial properties of Bifidobacterium adolescentis". mSphere. 10 (11) e00673-25. doi:10.1128/msphere.00673-25.
  29. ↑ Hao, Yanling; Huang, Dawei; Guo, Huiyuan; Xiao, Man; An, Haoran; Zhao, Liang; Zuo, Fanglei; Zhang, Bing; Hu, Songnian; Song, Shuhui; Chen, Shangwu; Ren, Fazheng (February 2011). "Complete Genome Sequence of Bifidobacterium longum subsp. longum BBMN68, a New Strain from a Healthy Chinese Centenarian". Journal of Bacteriology. 193 (3): 787–788. doi:10.1128/JB.01213-10. PMC 3021241. PMID 21097614.
  30. ↑ Ham, Jun-Sang; Lee, Taeheon; Byun, Mi-Jeong; Lee, Kyung-Tae; Kim, Min-Kyung; Han, Gi-Sung; Jeong, Seok-Geun; Oh, Mi-Hwa; Kim, Dong-Hun; Kim, Heebal (15 September 2011). "Complete Genome Sequence of Bifidobacterium longum subsp. longum KACC 91563". Journal of Bacteriology. 193 (18): 5044. doi:10.1128/JB.05620-11. PMC 3165663. PMID 21742881.
  31. ↑ Zakharevich, Natalia V.; Averina, Olga V.; Klimina, Ksenia M.; Kudryavtseva, Anna V.; Kasianov, Artem S.; Makeev, Vsevolod J.; Danilenko, Valery N. (October 2015). "Complete Genome Sequence of Bifidobacterium longum GT15: Identification and Characterization of Unique and Global Regulatory Genes". Microbial Ecology. 70 (3): 819–834. Bibcode:2015MicEc..70..819Z. doi:10.1007/s00248-015-0603-x.
  32. ↑ O’Callaghan, A.; Bottacini, F.; O’Connell Motherway, M.; van Sinderen, D. (December 2015). "Pangenome analysis of Bifidobacterium longum and site-directed mutagenesis through by-pass of restriction-modification systems". BMC Genomics. 16 (1) 832. Bibcode:2015BMCG...16..832O. doi:10.1186/s12864-015-1968-4. PMC 4618763.
  33. ↑ Inturri, Rosanna; Ventura, Marco; Ruas-Madiedo, Patricia; Lugli, Gabriele Andrea; Blandino, Giovanna (9 March 2017). "Complete Genome Sequence of Bifidobacterium longum W11 (LMG P-21586), Used as a Probiotic Strain". Genome Announcements. 5 (10) e01659-16. doi:10.1128/genomeA.01659-16. PMC 5347242.
  34. ↑ Inoue, Hikaru; Shibata, Sayaka; Ii, Konosuke; Inoue, Joe; Fukuda, Shinji; Arakawa, Kazuharu (28 May 2020). "Complete Genome Sequence of Bifidobacterium longum Strain Jih1, Isolated from Human Feces". Microbiology Resource Announcements. 9 (22) e00319-20. doi:10.1128/MRA.00319-20. PMC 7256257.
  35. ↑ Yamamoto, Isamu; Ueno, Yumiko; Geshi, Miho; Inagaki, Yoshishige; Odamaki, Toshitaka; Fujita, Kiyotaka (8 April 2021). "Complete Genome Sequence of Bifidobacterium longum subsp. longum JCM7052". Microbiology Resource Announcements. 10 (14) e01193-20. doi:10.1128/MRA.01193-20. PMC 8032470.
  36. ↑ Kim, You-Tae; Kim, Chul-Hong; Kwon, Joon-Gi; Cho, Jae Hyoung; Shin, Young-Sup; Kim, Hyeun Bum; Lee, Ju-Hoon (17 June 2022). "In vivo Trial of Bifidobacterium longum Revealed the Complex Network Correlations Between Gut Microbiota and Health Promotional Effects". Frontiers in Microbiology. 13 886934. doi:10.3389/fmicb.2022.886934. PMC 9247516.
  37. ↑ Van Haute, Mallory J.; Chacón-Vargas, Katherine; Yumul, Shara R. P.; Christensen, Chloe M.; Hutkins, Robert; Auchtung, Thomas A. (10 July 2026). "Complete genome sequence of Bifidobacterium longum subsp. longum strain iVE-15". Microbiology Resource Announcements e00202-26. doi:10.1128/mra.00202-26.
  38. ↑ Sela, D. A.; Chapman, J.; Adeuya, A.; Kim, J. H.; Chen, F.; Whitehead, T. R.; Lapidus, A.; Rokhsar, D. S.; Lebrilla, C. B.; German, J. B.; Price, N. P.; Richardson, P. M.; Mills, D. A. (2 December 2008). "The genome sequence of Bifidobacterium longum subsp. infantis reveals adaptations for milk utilization within the infant microbiome". Proceedings of the National Academy of Sciences. 105 (48): 18964–18969. Bibcode:2008PNAS..10518964S. doi:10.1073/pnas.0809584105. PMC 2596198.
  39. ↑ Chenoll, Empar; Rivero, Montserrat; Codoñer, Francisco M.; Martinez-Blanch, Juan F.; Ramón, Daniel; Genovés, Salvador; Moreno Muñoz, Jose Antonio (30 April 2015). "Complete Genome Sequence of Bifidobacterium longum subsp. infantis Strain CECT 7210, a Probiotic Strain Active against Rotavirus Infections". Genome Announcements. 3 (2) e00105-15. doi:10.1128/genomeA.00105-15. PMC 4384477.
  40. ↑ Peng, Yun-Yan; Zhong, Shu-Ying; Xu, Xi-Lin; Liu, Dong-Mei (November 2023). "Analysis of the safety and probiotic properties of Bifidobacterium longum B2-01 by complete genome sequencing combined with corresponding phenotypes". LWT. 189 115445. doi:10.1016/j.lwt.2023.115445.
  41. ↑ Li, Xiaoxia; Yang, Jianjun; Shi, Shaoqi; Lan, Hanglian; Zhao, Wen; Hung, Weilian; He, Jian; Wang, Ran (8 April 2024). "The Genome of Bifidobacterium longum subsp. infantis YLGB-1496 Provides Insights into Its Carbohydrate Utilization and Genetic Stability". Genes. 15 (4): 466. doi:10.3390/genes15040466.
  42. ↑ Fan, Pi-Chuan; Chua, Huey-Huey; Lin, Chia-Ray; Lai, Tzu-Hsuan; Chiou, Lih-Chu; Lee, Wang-Tso; Chen, Huey-Ling; Ni, Yen-Hsuan (31 December 2026). "Targeting the microbiome in pediatric migraine: gastrointestinal manifestations and the therapeutic role of Bifidobacterium longum". Gut Microbes. 18 (1) 2606487. doi:10.1080/19490976.2025.2606487.
  43. ↑ Lau, A.S.-Y.; Yanagisawa, N.; Hor, Y.-Y.; Lew, L.-C.; Ong, J.-S.; Chuah, L.-O.; Lee, Y.-Y.; Choi, S.-B.; Rashid, F.; Wahid, N.; Sugahara, H.; Xiao, J.-Z.; Liong, M.-T. (29 January 2018). "Bifidobacterium longum BB536 alleviated upper respiratory illnesses and modulated gut microbiota profiles in Malaysian pre-school children". Beneficial Microbes. 9 (1): 61–70. doi:10.3920/BM2017.0063.
  44. ↑ Xiao, J.-Z.; Kondo, S.; Yanagisawa, N.; Takahashi, N.; Odamaki, T.; Iwabuchi, N.; Miyaji, K.; Iwatsuki, K.; Togashi, H.; Enomoto, K.; Enomoto, T. (November 2006). "Probiotics in the treatment of Japanese cedar pollinosis: a double-blind placebo-controlled trial". Clinical & Experimental Allergy. 36 (11): 1425–1435. doi:10.1111/j.1365-2222.2006.02575.x.
  45. ↑ Takeda, Tsutomu; Asaoka, Daisuke; Nojiri, Shuko; Yanagisawa, Naotake; Nishizaki, Yuji; Osada, Taro; Koido, Shigeo; Nagahara, Akihito; Katsumata, Noriko; Odamaki, Toshitaka; Xiao, Jin-Zhong; Ohkusa, Toshifumi; Sato, Nobuhiro (March 2023). "Usefulness of Bifidobacterium longum BB536 in Elderly Individuals With Chronic Constipation: A Randomized Controlled Trial". American Journal of Gastroenterology. 118 (3): 561–568. doi:10.14309/ajg.0000000000002028. PMC 9973440.
  46. ↑ Whorwell, Peter J; Altringer, Linda; Morel, Jorge; Bond, Yvonne; Charbonneau, Duane; O'Mahony, Liam; Kiely, Barry; Shanahan, Fergus; Quigley, Eamonn M M (July 2006). "Efficacy of an Encapsulated Probiotic Bifidobacterium infantis 35624 in Women with Irritable Bowel Syndrome". The American Journal of Gastroenterology. 101 (7): 1581–1590. doi:10.1111/j.1572-0241.2006.00734.x.
  47. ↑ Pinto-Sanchez, Maria Ines; Hall, Geoffrey B.; Ghajar, Kathy; Nardelli, Andrea; Bolino, Carolina; Lau, Jennifer T.; Martin, Francois-Pierre; Cominetti, Ornella; Welsh, Christopher; Rieder, Amber; Traynor, Jenna; Gregory, Caitlin; De Palma, Giada; Pigrau, Marc; Ford, Alexander C.; Macri, Joseph; Berger, Bernard; Bergonzelli, Gabriela; Surette, Michael G.; Collins, Stephen M.; Moayyedi, Paul; Bercik, Premysl (August 2017). "Probiotic Bifidobacterium longum NCC3001 Reduces Depression Scores and Alters Brain Activity: A Pilot Study in Patients With Irritable Bowel Syndrome". Gastroenterology. 153 (2): 448–459.e8. doi:10.1053/j.gastro.2017.05.003.
  48. ↑ Tamaki, Hiroyuki; Nakase, Hiroshi; Inoue, Satoko; Kawanami, Chiharu; Itani, Toshinao; Ohana, Masaya; Kusaka, Toshihiro; Uose, Suguru; Hisatsune, Hiroshi; Tojo, Masahide; Noda, Teruyo; Arasawa, Souichi; Izuta, Masako; Kubo, Atsushi; Ogawa, Chikara; Matsunaka, Toshihiro; Shibatouge, Mitsushige (January 2016). "Efficacy of probiotic treatment with Bifidobacterium longum 536 for induction of remission in active ulcerative colitis: A randomized, double-blinded, placebo-controlled multicenter trial". Digestive Endoscopy. 28 (1): 67–74. doi:10.1111/den.12553.
  49. ↑ Yang, Yinyin; Gu, Xuhao; Liu, Chang; Zou, Li; Xie, Liwei; Liu, Yulong; Zhao, Peifeng; Tian, Ye; Cai, Shang (10 November 2025). "A phase II clinical trial of Bifidobacterium longum subsp. longum BL21 for preventing acute radiation enteritis among pelvic radiotherapy patients". Frontiers in Nutrition. 12 1626169. doi:10.3389/fnut.2025.1626169. PMC 12643464.
  50. ↑ Zhu, Chengsheng; Liu, Yinhua; Chen, Yanyan; Wang, Zhiying; Gao, Ya; Xu, Fei; Huang, Junyi (January 2026). "Probiotic Supplementation With Bifidobacterium longum Subsp. Longum BL21 Improves Glycemic Control and Modulates Gut Microbiota in Type 2 Diabetes: A Randomized Controlled Trial". Food Science & Nutrition. 14 (1) e71437. doi:10.1002/fsn3.71437.
  51. ↑ Choi, Yukyung; Kim, Ji-Eun; Kim, Kyung Hwan; Lee, Sunghee; Shin, Chang Hun (18 December 2025). "Glucose-Lowering Effects and Safety of Bifidobacterium longum CKD1 in Diabetic Dogs and Cats". Microorganisms. 13 (12): 2881. doi:10.3390/microorganisms13122881.
  52. ↑ Wang, Xiaoya; Xing, Zefeng; Wang, Rui; Zhang, Guoming; Liu, Guodong; Li, Zhen; Li, Lixiang (17 July 2025). "Multi-omics analyses the effect of Bifidobacterium longum subsp. longum BL21 supplementation on overweight and obese subjects: a randomized, double-blind, placebo-controlled study". Nutrition & Metabolism. 22 (1) 79. doi:10.1186/s12986-025-00969-2. PMC 12273011.
  53. ↑ Lewis, Erin D.; Antony, Joseph M.; Crowley, David C.; Piano, Amanda; Bhardwaj, Renu; Tompkins, Thomas A.; Evans, Malkanthi (21 April 2020). "Efficacy of Lactobacillus paracasei HA-196 and Bifidobacterium longum R0175 in Alleviating Symptoms of Irritable Bowel Syndrome (IBS): A Randomized, Placebo-Controlled Study". Nutrients. 12 (4): 1159. doi:10.3390/nu12041159. PMC 7230591.
  54. ↑ Shi, Shaoqi; Zhang, Qi; Sang, Yue; Ge, Shaoyang; Wang, Qi; Wang, Ran; He, Jingjing (22 December 2022). "Probiotic Bifidobacterium longum BB68S Improves Cognitive Functions in Healthy Older Adults: A Randomized, Double-Blind, Placebo-Controlled Trial". Nutrients. 15 (1): 51. doi:10.3390/nu15010051. PMC 9824790.
  55. ↑ Bercik, P.; Park, A. J.; Sinclair, D.; Khoshdel, A.; Lu, J.; Huang, X.; Deng, Y.; Blennerhassett, P. A.; Fahnestock, M.; Moine, D.; Berger, B.; Huizinga, J. D.; Kunze, W.; McLean, P. G.; Bergonzelli, G. E.; Collins, S. M.; Verdu, E. F. (December 2011). "The anxiolytic effect of Bifidobacterium longum NCC3001 involves vagal pathways for gut-brain communication". Neurogastroenterology & Motility. 23 (12): 1132–1139. doi:10.1111/j.1365-2982.2011.01796.x. PMC 3413724. PMID 21988661.
  56. ↑ Fukuda, Shinji; Toh, Hidehiro; Hase, Koji; Oshima, Kenshiro; Nakanishi, Yumiko; Yoshimura, Kazutoshi; Tobe, Toru; Clarke, Julie M.; Topping, David L.; Suzuki, Tohru; Taylor, Todd D.; Itoh, Kikuji; Kikuchi, Jun; Morita, Hidetoshi; Hattori, Masahira; Ohno, Hiroshi (January 2011). "Bifidobacteria can protect from enteropathogenic infection through production of acetate". Nature. 469 (7331): 543–547. Bibcode:2011Natur.469..543F. doi:10.1038/nature09646.
  57. ↑ Chen, Yang; Chen, Haiqin; Ding, Jiuhong; Stanton, Catherine; Ross, R. Paul; Zhao, Jianxin; Zhang, Hao; Yang, Bo; Chen, Wei (8 December 2021). "Bifidobacterium longum Ameliorates Dextran Sulfate Sodium-Induced Colitis by Producing Conjugated Linoleic Acid, Protecting Intestinal Mechanical Barrier, Restoring Unbalanced Gut Microbiota, and Regulating the Toll-Like Receptor-4/Nuclear Factor-κB Signaling Pathway". Journal of Agricultural and Food Chemistry. 69 (48): 14593–14608. Bibcode:2021JAFC...6914593C. doi:10.1021/acs.jafc.1c06176.
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