The DOI matches its Crossref record; 34 of the 34 references it cites were found in a registry or an index.
Generation of NO by probiotic bacteria in the gastrointestinal tract
Abstract
Probiotic bacteria elicit a number of beneficial effects in the gut but the mechanisms for these health promoting effects are not entirely understood. Recent in vitro data suggest that lactobacilli can utilise nitrate and nitrite to generate nitric oxide, a gas with immunomodulating and antibacterial properties. Here we further characterised intestinal NO generation by bacteria. In rats, dietary supplementation with lactobacilli and nitrate resulted in a 3-8 fold NO increase in the small intestine and caecum, but not in colon. Caecal NO levels correlated to nitrite concentration in luminal contents. In neonates, colonic NO levels correlated to the nitrite content of breast milk and faeces. Lactobacilli and bifidobacteria isolated from the stools of two neonates, generated NO from nitrite in vitro, whereas S. aureus and E. coli rapidly consumed NO. We here show that commensal bacteria can be a significant source of NO in the gut in addition to the mucosal NO production. Intestinal NO generation can be stimulated by dietary supplementation with substrate and lactobacilli. The generation of NO by some probiotic bacteria can be counteracted by rapid NO consumption by other strains. Future studies will clarify the biological role of the bacteria-derived intestinal NO in health and disease.
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In the citing paper
“Similarly, there was decreased NO generation in a polymicrobial culture containing NO-consuming bacteria in rats[217].”
From Enterosalivary nitrate metabolism and the microbiome: Intersection of microbial metabolism, nitric oxide and diet in cardiac and pulmonary vascular health (2017) · cites this paper as [217]
In the citing paper
“commensal gut bacteria are able to directly produce NO and also modify NO production, potentially influencing regional blood flow, mucosal integrity, microbial diversity, and effective nitrate and nitrite uptake.”
From Enterosalivary nitrate metabolism and the microbiome: Intersection of microbial metabolism, nitric oxide and diet in cardiac and pulmonary vascular health (2017) · cites this paper as [217]
In the citing paper
“Many bacteria are capable of reducing nitrate to nitrite to NO via the denitrification pathway.”
From Enterosalivary nitrate metabolism and the microbiome: Intersection of microbial metabolism, nitric oxide and diet in cardiac and pulmonary vascular health (2017) · cites this paper as [217]
In the citing paper
“while Lactobacilli, Escherichia coli and Salmonella typhimurium all increase cecal NO production when supplied with nitrate[217,233,271,278].”
From Enterosalivary nitrate metabolism and the microbiome: Intersection of microbial metabolism, nitric oxide and diet in cardiac and pulmonary vascular health (2017) · cites this paper as [217]
In the citing paper
“both Lactobacilli and Bifidobacteria have been shown to generate NO from nitrite in culture”
From Enterosalivary nitrate metabolism and the microbiome: Intersection of microbial metabolism, nitric oxide and diet in cardiac and pulmonary vascular health (2017) · cites this paper as [217]
In the citing paper
“In polymicrobial environments, Lactobacilli engage in advantageous, mutualistic interactions with other bacteria to survive under hypoxia and alter NO generation[217,413]”
From Enterosalivary nitrate metabolism and the microbiome: Intersection of microbial metabolism, nitric oxide and diet in cardiac and pulmonary vascular health (2017) · cites this paper as [217]
In the citing paper
“the commonly available probiotic strain, L. rhamnosus, is capable of reducing nitrate to nitrite[217]”
From Enterosalivary nitrate metabolism and the microbiome: Intersection of microbial metabolism, nitric oxide and diet in cardiac and pulmonary vascular health (2017) · cites this paper as [217]
In the citing paper
“producing NO in the gut in response to oral nitrate administration[74,217,278]”
From Enterosalivary nitrate metabolism and the microbiome: Intersection of microbial metabolism, nitric oxide and diet in cardiac and pulmonary vascular health (2017) · cites this paper as [217]
In the citing paper
“More recently, the normal bacterial flora has been shown to generate NO and gut luminal NO levels have been measured in vivo in rats [15,16].”
From Nitrate reduction to nitrite, nitric oxide and ammonia by gut bacteria under physiological conditions (2015) · cites this paper as [16]
Citations
Cites
Nitrite reduction to nitric oxide by deoxyhemoglobin vasodilates the human circulation
Cosby, K., Partovi, K. S., Crawford, J. H., Patel, R. P., Reiter, C. D., Martyr, S., Yang, B. K., Waclawiw, M. A., Zalos, G., Xu, X., et al. (2003) · Nature Medicine · doi:10.1038/nm954 · Cited by 1,807
Nitrate, bacteria and human health
Lundberg, J. O., Weitzberg, E., Cole, J. A., & Benjamin, N. (2004) · Nature Reviews Microbiology · doi:10.1038/nrmicro929 · Cited by 739
Self-citationDuncan, C., Dougall, H., Johnston, P., Green, S., Brogan, R., Leifert, C., Smith, L., Golden, M., & Benjamin, N. (1995) · Nature Medicine · doi:10.1038/nm0695-546 · Cited by 734
Cytoprotective effects of nitrite during in vivo ischemia-reperfusion of the heart and liver
Duranski, M. R., Greer, J. J. M., Dejam, A., Jaganmohan, S., Hogg, N., Langston, W., Patel, R. P., Yet, S.-F., Wang, X., Kevil, C. G., et al. (2005) · Journal of Clinical Investigation · doi:10.1172/jci22493 · Cited by 674
Benjamin, N., O'Driscoll, F., Dougall, H., Duncan, C., Smith, L., Golden, M., & McKenzie, H. (1994) · Nature · doi:10.1038/368502a0 · Cited by 665
Intragastric nitric oxide production in humans: measurements in expelled air.
Lundberg, J. O., Weitzberg, E., Lundberg, J. M., & Alving, K. (1994) · Gut · doi:10.1136/gut.35.11.1543 · Cited by 661
Self-citationInorganic nitrate is a possible source for systemic generation of nitric oxide
Lundberg, J. O., & Govoni, M. (2004) · Free Radical Biology and Medicine · doi:10.1016/j.freeradbiomed.2004.04.027 · Cited by 657
Self-citationThe emerging biology of the nitrite anion
Gladwin, M. T., Schechter, A. N., Kim-Shapiro, D. B., Patel, R. P., Hogg, N., Shiva, S., Cannon, R. O., Kelm, M., Wink, D. A., Espey, M. G., et al. (2005) · Nature Chemical Biology · doi:10.1038/nchembio1105-308 · Cited by 609
Self-citationWebb, A., Bond, R., McLean, P., Uppal, R., Benjamin, N., & Ahluwalia, A. (2004) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.0402927101 · Cited by 608
Non-Enzymatic Nitric Oxide Synthesis in Biological Systems
Zweier, J. L., Samouilov, A., & Kuppusamy, P. (1999) · Biochimica et Biophysica Acta (BBA) - Bioenergetics · doi:10.1016/s0005-2728(99)00018-3 · Cited by 363
Evaluation of bacterial nitrate reduction in the human oral cavity
Doel, J. J., Benjamin, N., Hector, M. P., Rogers, M., & Allaker, R. P. (2005) · European Journal of Oral Sciences · doi:10.1111/j.1600-0722.2004.00184.x · Cited by 362
Fatty Acid Transduction of Nitric Oxide Signaling
Baker, P. R. S., Lin, Y., Schopfer, F. J., Woodcock, S. R., Groeger, A. L., Batthyany, C., Sweeney, S., Long, M. H., Iles, K. E., Baker, L. M. S., et al. (2005) · Journal of Biological Chemistry · doi:10.1074/jbc.m504212200 · Cited by 358
Nitrite‐derived nitric oxide: a possible mediator of ‘acidic–metabolic’ vasodilation
Modin, A., Björne, H., Herulf, M., Alving, K., Weitzberg, E., & Lundberg, J. O. N. (2001) · Acta Physiologica Scandinavica · doi:10.1046/j.1365-201x.2001.00771.x · Cited by 346
Self-citationNO Generation From Nitrite and Its Role in Vascular Control
Lundberg, J. O., & Weitzberg, E. (2005) · Arteriosclerosis, Thrombosis, and Vascular Biology · doi:10.1161/01.atv.0000161048.72004.c2 · Cited by 341
Self-citationInhibitors of endogenous nitrosation mechanisms and implications in human cancer prevention
Bartsch, H., Ohshima, H., & Pignatelli, B. (1988) · Mutation Research - Fundamental and Molecular Mechanisms of Mutagenesis · doi:10.1016/0027-5107(88)90194-7 · Cited by 296
Nonenzymatic Nitric Oxide Production in Humans
Weitzberg, E., & Lundberg, J. O. N. (1998) · Nitric Oxide · doi:10.1006/niox.1997.0162 · Cited by 296
Self-citationGreatly increased luminal nitric oxide in ulcerative colitis
Lundberg, J. O. N., Lundberg, J. M., Alving, K., & Hellström, P. M. (1994) · The Lancet · doi:10.1016/s0140-6736(94)90460-x · Cited by 266
Self-citationNitrite in saliva increases gastric mucosal blood flow and mucus thickness
Björne, H., Petersson, J., Phillipson, M., Weitzberg, E., Holm, L., & Lundberg, J. O. (2004) · Journal of Clinical Investigation · doi:10.1172/jci19019 · Cited by 246
Self-citationCole, J. (1996) · FEMS Microbiology Letters · doi:10.1111/j.1574-6968.1996.tb08017.x · Cited by 195
Carlsson, S., Wiklund, N. P., Engstrand, L., Weitzberg, E., & Lundberg, J. O. N. (2001) · Nitric Oxide · doi:10.1006/niox.2001.0371 · Cited by 189
Self-citationCardioprotective effects of vegetables: is nitrate the answer?
Lundberg, J. O., Feelisch, M., Björne, H., Jansson, E. Å., & Weitzberg, E. (2006) · Nitric Oxide · doi:10.1016/j.niox.2006.01.013 · Cited by 185
Self-citationGastrointestinal bacteria generate nitric oxide from nitrate and nitrite
Sobko, T., Reinders, C. I., Jansson, E. Å., Norin, E., Midtvedt, T., & Lundberg, J. O. (2005) · Nitric Oxide · doi:10.1016/j.niox.2005.08.002 · Cited by 160
Self-citationHigh Rate of Transfer of Staphylococcus aureus from Parental Skin to Infant Gut Flora
Lindberg, E., Adlerberth, I., Hesselmar, B., Saalman, R., Strannegård, I., Åberg, N., & Wold, A. E. (2004) · Journal of Clinical Microbiology · doi:10.1128/jcm.42.2.530-534.2004 · Cited by 108
Bengmark, S. (2005) · Gastroenterology Clinics of North America · doi:10.1016/j.gtc.2005.05.002 · Cited by 90
Herulf, M. (1998) · Scandinavian Journal of Gastroenterology · doi:10.1080/00365529850166897 · Cited by 78
Gastrointestinal nitric oxide generation in germ-free and conventional rats
Sobko, T., Reinders, C., Norin, E., Midtvedt, T., Gustafsson, L. E., & Lundberg, J. O. (2004) · American Journal of Physiology-Gastrointestinal and Liver Physiology · doi:10.1152/ajpgi.00203.2004 · Cited by 75
Self-citationNitric oxide and inflammation: The answer is blowing in the wind
Lundberg, J. O., Lundberg, J. M., Alving, K., & Weitzberg, E. (1997) · Nature Medicine · doi:10.1038/nm0197-30 · Cited by 70
Self-citationNitric oxide released by lactobacillus farciminis improvesTNBS‐induced colitis in rats
Lamine, F., Fioramonti, J., Bueno, L. P., Nepveu, F., Cauquil, E., Lobysheva, I. I., Eutamène, H., & Théodorou, V. (2004) · Scandinavian Journal of Gastroenterology · doi:10.1080/00365520310007152 · Cited by 68
Evaluation of nitric oxide production by lactobacilli
Xu, J., & Verstraete, W. (2001) · Applied Microbiology and Biotechnology · doi:10.1007/s002530100616 · Cited by 67
Reinders, C. I., Herulf, M., Ljung, T., Hollenberg, J., Weitzberg, E., Lundberg, J. O., & Hellström, P. M. (2005) · Clinical Gastroenterology and Hepatology · doi:10.1016/s1542-3565(05)00182-5 · Cited by 64
Self-citationWolf, G., Arendt, E. K., Pfähler, U., & Hammes, W. P. (1990) · International Journal of Food Microbiology · doi:10.1016/0168-1605(90)90079-k · Cited by 44
Nitric oxide may trigger lactation in humans
Iizuka, T., Sasaki, M., Oishi, K., Uemura, S., Koike, M., & Minatogawa, Y. (1997) · The Journal of Pediatrics · doi:10.1016/s0022-3476(97)70030-1 · Cited by 28
Sobko, T., Norman, M., Norin, E. L., Gustafsson, L. E., & Lundberg, J. O. (2005) · Allergy · doi:10.1111/j.1398-9995.2005.00737.x · Cited by 19
Self-citationN‐nitrosodimethylamine, nitrate and nitrate‐reducing microorganisms in human milk
Uibu, J., Tauts, O., Levin, A., Shimanovskaya, N. P., & Matto, R. (1996) · Acta Paediatrica · doi:10.1111/j.1651-2227.1996.tb18217.x · Cited by 8
Research works printed but not linked: 1
- Reinders, 2005, Rectal NO for differentiation between IBD and irritable bowel syndrome, Clin. Gastroenterol., 8, 777
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Sorted by citations
The gut-brain axis: interactions between enteric microbiota, central and enteric nervous systems.
(2015) · PubMed Central · Cited by 2,540
Food sources of nitrates and nitrites: The physiologic context for potential health benefits
Hord, N. G., Tang, Y., & Bryan, N. S. (2009) · The American Journal of Clinical Nutrition · doi:10.3945/ajcn.2008.27131 · Cited by 1,069
Gut microbiota imbalance and colorectal cancer
Gagnière, J. (2016) · World Journal of Gastroenterology · doi:10.3748/wjg.v22.i2.501 · Cited by 890
Microbiome, probiotics and neurodegenerative diseases: deciphering the gut brain axis
Westfall, S., Lomis, N., Kahouli, I., Dia, S. Y., Singh, S. P., & Prakash, S. (2017) · Cellular and Molecular Life Sciences · doi:10.1007/s00018-017-2550-9 · Cited by 570
Analysis of Gut Microbiota in Patients with Parkinson’s Disease
Petrov, V. A., Saltykova, I. V., Zhukova, I. A., Alifirova, V. M., Zhukova, N. G., Dorofeeva, Y. B., Tyakht, A. V., Kovarsky, B. A., Alekseev, D. G., Kostryukova, E. S., et al. (2017) · Bulletin of Experimental Biology and Medicine · doi:10.1007/s10517-017-3700-7 · Cited by 487
Metadata
- Authors
- Sobko, T., Huang, L., Midtvedt, T., Norin, E., Gustafsson, L. E., Norman, M., Jansson, E. Å., & Lundberg, J. O.
- Affiliations
- Karolinska Institutet (SE)
- Corresponding author
- Sobko, Tanja
- Venue
- Free Radical Biology and Medicine
- Publisher
- Elsevier BV
- Published
- 2006-09
- Volume
- 41
- Issue
- 6
- Pages
- 985-991
- ISSN
- 0891-5849 (ISSN-L)
- OpenAlex
- W2093280926
- Cited by
- 118
- References
- 34
- Citations by year
- 2026: 2 · 2025: 3 · 2024: 6 · 2023: 6 · 2022: 8 · 2021: 6 · 2020: 7 · 2019: 6 · 2018: 9 · 2017: 9 · 2016: 13 · 2015: 7 · 2014: 6 · 2013: 3 · 2012: 6
- FWCI
- 8.05
- Type
- journal article
- Language
- en
- Open access
- closed
- Licence
- Locations
- Free Radical Biology and Medicine (publishedVersion)
- PubMed (publishedVersion)
- The HKU Scholars Hub (University of Hong Kong) (submittedVersion)
- Funders
- European Commission
- Hjärt-Lungfonden
- Vetenskapsrådet
- Ekhagastiftelsen
- Topics
- Life Sciences › Agricultural and Biological Sciences › Food Science › Probiotics and Fermented Foods
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Gut microbiota and health
- Health Sciences › Nursing › Nutrition and Dietetics › Infant Nutrition and Health
- Keywords
- nitric oxide, probiotic bacteria, lactobacilli, Bifidobacterium, nitrate, nitrite, gastrointestinal tract, commensal bacteria, nitrate supplementation, neonates, breast milk, cecum, small intestine, Staphylococcus aureus, Escherichia coli, gut microbiota
- MeSH terms
- Animals, Cecum, Colon, Female, Gastric Mucosa, Humans, Infant, Newborn, Intestine, Small, Male, Nitric Oxide, Stomach, Rats, Wistar, Probiotics, Delivery, Obstetric, Rats, Lacticaseibacillus rhamnosus
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