Bifidobacterium longum

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Bifidobacterium longum
Bifidobacterium longum en microscopie electronique.jpg
Scientific classification OOjs UI icon edit-ltr.svg
Domain: Bacteria
Phylum: Actinomycetota
Class: Actinomycetia
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 Representative morphologic characteristics of B. longum subsp. longum strains.jpg
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

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]

Environment

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] [11] 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] [12] This adhesion is also enhanced by the fatty acids in the lipoteichoic acid of the B. longum cell wall. [12]

Metabolism

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. [13] 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. [14]

Pathogenesis

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, [15] [16] [17] although there are also reports of infection in adults. [18] [19] [20] Infection in preterm infants manifests as bacteremia or necrotizing enterocolitis, [21] while in adults there have been reports of sepsis and peritonitis. [18] [20]

Research

B. longum is a constituent in VSL#3.

Immune system regulation

The use of B. longum was shown to shorten the duration and minimize the severity of symptoms associated with the common cold with a similar effect to that of neuraminidase inhibitors for influenza. [22]

Bifidobacterium longum 35624

Bifidobacterium longum ssp. longum 35624, previously classified as Bifidobacterium longum ssp. infantis 35624, classified as Bifidobacterium infantis 35624 before that and still marketed as such. It is sold under the brand name Align in the US and Canada and Alflorex in Ireland, the UK and other European countries. It is patented. This strain was isolated directly from the epithelium of the terminal ileum of a healthy human subject, and is one of the most researched probiotic strains. [23] Large scale clinical trials have shown that the strain is effective in controlling the symptoms of IBS including bloating, diarrhoea, abdominal pain and discomfort. [24]

Bifidobacterium longum BB536

Bifidobacterium longum BB536 was discovered in the intestines of healthy breastfed infants in 1969. [25] It is often used in nutritional supplement. In some small clinical trials, it has been shown to help defecation and relieve lactose intolerance symptoms. [26] [27]

See also

Related Research Articles

<span class="mw-page-title-main">Human microbiome</span> Microorganisms in or on human skin and biofluids

The human microbiome is the aggregate of all microbiota that reside on or within human tissues and biofluids along with the corresponding anatomical sites in which they reside, including the gastrointestinal tract, skin, mammary glands, seminal fluid, uterus, ovarian follicles, lung, saliva, oral mucosa, conjunctiva, and the biliary tract. Types of human microbiota include bacteria, archaea, fungi, protists, and viruses. Though micro-animals can also live on the human body, they are typically excluded from this definition. In the context of genomics, the term human microbiome is sometimes used to refer to the collective genomes of resident microorganisms; however, the term human metagenome has the same meaning.

<span class="mw-page-title-main">Probiotic</span> Microorganisms said to provide health benefits when consumed

Probiotics are live microorganisms promoted with claims that they provide health benefits when consumed, generally by improving or restoring the gut microbiota. Probiotics are considered generally safe to consume, but may cause bacteria-host interactions and unwanted side effects in rare cases. There is some evidence that probiotics are beneficial for some conditions, but there is little evidence for many of the health benefits claimed for them.

<i>Lactobacillus acidophilus</i> Species of bacterium

Lactobacillus acidophilus is a rod-shaped, Gram-positive, homofermentative, anaerobic microbe first isolated from infant feces in the year 1900. The species commonly found in humans, specifically the gastrointestinal tract and oral cavity as well as various fermented foods such as fermented milk or yogurt. The species most readily grows at low pH levels, and has an optimum growth temperature of 37 °C. Certain strains of L. acidophilus show strong probiotic effects, and are commercially used in dairy production. The genome of L. acidophilus has been sequenced.

<span class="mw-page-title-main">Gut microbiota</span> Community of microorganisms in the gut

Gut microbiota, gut microbiome, or gut flora are the microorganisms, including bacteria, archaea, fungi, and viruses, that live in the digestive tracts of animals. The gastrointestinal metagenome is the aggregate of all the genomes of the gut microbiota. The gut is the main location of the human microbiome. The gut microbiota has broad impacts, including effects on colonization, resistance to pathogens, maintaining the intestinal epithelium, metabolizing dietary and pharmaceutical compounds, controlling immune function, and even behavior through the gut–brain axis.

<i>Lacticaseibacillus rhamnosus</i> Species of bacterium

Lacticaseibacillus rhamnosus is a bacterium that originally was considered to be a subspecies of L. casei, but genetic research found it to be a separate species in the L. casei clade, which also includes L. paracasei and L. zeae. It is a short Gram-positive homofermentative facultative anaerobic non-spore-forming rod that often appears in chains. Some strains of L. rhamnosus bacteria are being used as probiotics, and are particularly useful in treating infections of the female urogenital tract, most particularly very difficult to treat cases of bacterial vaginosis. The species Lacticaseibacillus rhamnosus and Limosilactobacillus reuteri are commonly found in the healthy female genito-urinary tract and are helpful to regain control of dysbiotic bacterial overgrowth during an active infection. L. rhamnosus sometimes is used in dairy products such as fermented milk and as non-starter-lactic acid bacterium (NSLAB) in long-ripened cheese. While frequently considered a beneficial organism, L. rhamnosus may not be as beneficial to certain subsets of the population; in rare circumstances, especially those primarily involving weakened immune system or infants, it may cause endocarditis. Despite the rare infections caused by L. rhamnosus, the species is included in the list of bacterial species with qualified presumed safety (QPS) status of the European Food Safety Agency.

Streptococcus bovis is a species of Gram-positive bacteria that in humans is associated with urinary tract infections, endocarditis, sepsis, and colorectal cancer. S. gallolyticus is commonly found in the alimentary tract of cattle, sheep, and other ruminants, and may cause ruminal acidosis or feedlot bloat. It is also associated with spontaneous bacterial peritonitis, a frequent complication occurring in patients affected by cirrhosis. Equivalence with Streptococcus equinus has been contested.

<i>Bifidobacterium animalis</i> Species of bacterium

Bifidobacterium animalis is a gram-positive, anaerobic, rod-shaped bacterium of the Bifidobacterium genus which can be found in the large intestines of most mammals, including humans.

<i>Bacteroides fragilis</i> Species of bacterium

Bacteroides fragilis is an anaerobic, Gram-negative, pleomorphic to rod-shaped bacterium. It is part of the normal microbiota of the human colon and is generally commensal, but can cause infection if displaced into the bloodstream or surrounding tissue following surgery, disease, or trauma.

Limosilactobacillus reuteri is a lactic acid bacterium found in a variety of natural environments, including the gastrointestinal tract of humans and other animals. It does not appear to be pathogenic and may have health effects.

Levilactobacillus brevis is a gram-positive, rod shaped species of lactic acid bacteria which is heterofermentative, creating CO2, lactic acid and acetic acid or ethanol during fermentation. L. brevis is the type species of the genus Levilactobacillus (previously L. brevis group), which comprises 24 species. It can be found in many different environments, such as fermented foods, and as normal microbiota. L. brevis is found in food such as sauerkraut and pickles. It is also one of the most common causes of beer spoilage. Ingestion has been shown to improve human immune function, and it has been patented several times. Normal gut microbiota L. brevis is found in human intestines, vagina, and feces.

<i>Pediococcus acidilactici</i> Species of bacterium

Pediococcus acidilactici is a species of Gram-positive cocci that is often found in pairs or tetrads. P. acidilactici is a homofermentative bacterium that can grow in a wide range of pH, temperature, and osmotic pressure, therefore being able to colonize the digestive tract. It has emerged as a potential probiotic that has shown promising results in animal and human experiments, though some of the results are limited. They are commonly found in fermented vegetables, fermented dairy products, and meat.

<i>Bifidobacterium</i> Genus of bacteria

Bifidobacterium is a genus of gram-positive, nonmotile, often branched anaerobic bacteria. They are ubiquitous inhabitants of the gastrointestinal tract though strains have been isolated from the vagina and mouth of mammals, including humans. Bifidobacteria are one of the major genera of bacteria that make up the gastrointestinal tract microbiota in mammals. Some bifidobacteria are used as probiotics.

<i>Lacticaseibacillus paracasei</i> Species of bacterium

Lacticaseibacillus paracasei (commonly abbreviated as Lc. paracasei) is a gram-positive, homofermentative species of lactic acid bacteria that are commonly used in dairy product fermentation and as probiotic cultures. Lc. paracasei is a bacterium that operates by commensalism. It is commonly found in many human habitats such as human intestinal tracts and mouths as well as sewages, silages, and previously mentioned dairy products. The name includes morphology, a rod-shaped bacterium with a width of 2.0 to 4.0μm and length of 0.8 to 1.0μm.

<i>Lactobacillus bulgaricus</i> GLB44 Subspecies of bacterium

Lactobacillus delbrueckii subsp. bulgaricus is a bacterial subspecies traditionally isolated from European yogurts. Lactobacillus bulgaricusGLB44 differs from other L. bulgaricus strains because it was isolated from the leaves of Galanthus nivalis in Bulgaria.

Bifidobacterium breve is a bacterial species of the genus Bifidobacterium which has probiotic properties. Bifidobacteria are a type of bacteria that live symbiotically in the intestines of humans. They have been used to treat a number of conditions including constipation, diarrhea, irritable bowel syndrome and even the cold and flu. Some of these uses have been backed up by scientific research, but others have not. B. breve is a gram positive, anaerobic, rod shaped organism that is non motile and forms branches with its neighbors.

Psychobiotics is a term used in preliminary research to refer to live bacteria that, when ingested in appropriate amounts, might confer a mental health benefit by affecting microbiota of the host organism. Whether bacteria might play a role in the gut-brain axis is under research. A 2020 literature review suggests that the consumption of psychobiotics could be considered as a viable option to restore mental health although lacking randomized controlled trials on clear mental health outcomes in humans.

Proteobiotics are natural metabolites which are produced by fermentation process of specific probiotic strains. These small oligopeptides were originally discovered in and isolated from culture media used to grow probiotic bacteria and may account for some of the health benefits of probiotics.

<span class="mw-page-title-main">Human milk microbiome</span> Community of microorganisms in human milk

The human milk microbiota, also known as human milk probiotics (HMP), encompasses the microbiota–the community of microorganisms–present within the human mammary glands and breast milk. Contrary to the traditional belief that human breast milk is sterile, advancements in both microbial culture and culture-independent methods have confirmed that human milk harbors diverse communities of bacteria. These communities are distinct in composition from other microbial populations found within the human body which constitute the human microbiome.

Postbiotics - also known as metabiotics, biogenics, or simply metabolites - are soluble factors, secreted by live bacteria, or released after bacterial lysis providing physiological benefits to the host.

Lacto-<i>N</i>-tetraose Chemical compound

Lacto-N-tetraose is a complex sugar found in human milk. It is one of the few characterized human milk oligosaccharides (HMOs) and is enzymatically synthesized from the substrate lactose. It is biologically relevant in the early development of the infant gut flora.

References

  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 .
  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. 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. 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.
  12. 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.
  13. 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.
  14. 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.
  15. 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.
  16. 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.
  17. 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.
  18. 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.
  19. 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.
  20. 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.
  21. 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.
  22. De Vrese, M.; Winkler, P.; Rautenberg, P.; Harder, T.; Noah, C.; Laue, C.; Ott, S.; Hampe, J.; Schreiber, S.; Heller, K.; Schrezenmeir, J. R. (2005). "Effect of Lactobacillus gasseri PA 16/8, Bifidobacterium longum SP 07/3, B. Bifidum MF 20/5 on common cold episodes: A double blind, randomized, controlled trial". Clinical Nutrition. 24 (4): 481–491. doi:10.1016/j.clnu.2005.02.006. PMID   16054520.
  23. "Bifantis (Bifidobacterium infantis 35624) – Professional Monograph" (PDF). Procter & Gamble. 2007. Archived from the original (PDF) on 7 March 2017. Retrieved 4 January 2018.
  24. 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. PMID   16863564. S2CID   3352959.
  25. Minami, Miki; Tsuji, Shoji; Akagawa, Shohei; Akagawa, Yuko; Yoshimoto, Yuki; Kawakami, Hirosato; Kohno, Mamiko; Kaneko, Kazunari (2022-11-15). "Effect of a Bifidobacterium-Containing Acid-Resistant Microcapsule Formulation on Gut Microbiota: A Pilot Study". Nutrients. 14 (22): 4829. doi: 10.3390/nu14224829 . ISSN   2072-6643. PMC   9693766 . PMID   36432516.
  26. 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. ISSN   0002-9270. PMC   9973440 . PMID   36216361.
  27. Vitellio, Paola; Celano, Giuseppe; Bonfrate, Leonilde; Gobbetti, Marco; Portincasa, Piero; De Angelis, Maria (2019-04-19). "Effects of Bifidobacterium longum and Lactobacillus rhamnosus on Gut Microbiota in Patients with Lactose Intolerance and Persisting Functional Gastrointestinal Symptoms: A Randomised, Double-Blind, Cross-Over Study". Nutrients. 11 (4): 886. doi: 10.3390/nu11040886 . ISSN   2072-6643. PMC   6520754 . PMID   31010241.