Probiotics and the gut microbiota in intestinal health and disease
Open accessAbstract
The use of probiotics is increasing in popularity for both the prevention and treatment of a variety of diseases. While a growing number of well-conducted, prospective, randomized, controlled, clinical trials are emerging and investigations of underlying mechanisms of action are being undertaken, questions remain with respect to the specific immune and physiological effects of probiotics in health and disease. This Review considers recent advances in clinical trials of probiotics for intestinal disorders in both adult and pediatric populations. An overview of recent in vitro and in vivo research related to potential mechanisms of action of various probiotic formulations is also considered.
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- Premisecitation
Breastfeeding lowers intestinal permeability in human infants relative to formula feeding.
“Breastfeeding reduces intestinal permeability in human infants compared with formula feeding.8”
Quote in the paperNot a substantial claim0 of 1 sources checked- cites [8] Taylor, S. N., Basile, L. A., Ebeling, M. & Wagner, C. L. Intestinal permeability in preterm infants by feeding type: mother's milk versus formula. Breastfeed. Med. 4, 11–15 (2009). source
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- Premisecitation
The gut microbial ecosystem acts like a virtual organ system that supports host nutrition and homeostasis.
“This microbial ecosystem has the ability to function as a ‘virtual’ organ system3 that aids host nutrition and maintenance of homeostasis.”
Quote in the paperNot a substantial claim0 of 1 sources checked- cites [3] Forsythe, P., Sudo, N., Dinan, T., Taylor, V. H. & Bienenstock, J. Mood and gut feelings. Brain Behav. Immun. 24, 9–16 (2010). source
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- Premisecitation
Caesarean delivery is linked to greater colonization by Klebsiella, Enterobacter, and Clostridia.
“By contrast, caesarean section births are associated with increased colonization by Klebsiella, Enterobacter and Clostridia,7 which are organisms prevalent in hospital settings.”
Quote in the paperNot a substantial claim0 of 1 sources checked- cites [7] Conroy, M. E., Shi, H. N. & Walker, W. A. The long-term health effects of neonatal microbial flora. Curr. Opin. Allergy Clin. Immunol. 9, 197–201 (2009). source
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- Premisecitation
Formula feeding is linked to more Clostridia and Bacteroides in the intestinal tract.
“Formula feeding is associated with an increased presence of both Clostridia and Bacteroides in the intestinal tract.7”
Quote in the paperNot a substantial claim0 of 1 sources checked- cites [7] Conroy, M. E., Shi, H. N. & Walker, W. A. The long-term health effects of neonatal microbial flora. Curr. Opin. Allergy Clin. Immunol. 9, 197–201 (2009). source
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- Premisecitation
Microbiota development in early infancy is shaped by delivery mode, gestational age, and perinatal antibiotic use.
“Development of the microbiota occurs in early infancy, and is influenced by route of delivery (vaginal versus caesarean section), gestational age (prematurity versus full term), and use of antibiotics in the perinatal period, especially in the neonatal intensive care unit setting.”
Quote in the paperNot a substantial claim0 of 3 sources checked- cites [5] Ley, R. E., Peterson, D. A. & Gordon, J. I. Ecological and evolutionary forces shaping microbial diversity in the human intestine. Cell 124, 837–848 (2006). source
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- cites [6] Chen, J., Cai, W. & Feng, Y. Development of intestinal bifidobacteria and lactobacilli in breast-fed neonates. Clin. Nutr. 26, 559–566 (2007). source
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- cites [7] Conroy, M. E., Shi, H. N. & Walker, W. A. The long-term health effects of neonatal microbial flora. Curr. Opin. Allergy Clin. Immunol. 9, 197–201 (2009). source
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- Premisecitation
B. lactis DN-173-010 improved altered gut motility in IBS patients.
“Altered gut motility was ameliorated in another study of Bifidobacterium lactis, strain DN-173-010, in patients with IBS.”
Quote in the paperNot a substantial claim0 of 1 sources checked- cites [31] Agrawal, A. et al. Clinical trial: the effects of a fermented milk product containing Bifidobacterium lactis DN-173-010 on abdominal distension and gastrointestinal transit in irritable bowel syndrome with constipation. Aliment. Pharmacol. Ther. 29, 104–114 (2008). source
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- Premisecitation
An L. lactis strain modified to secrete IL-10 in the colon directly modulates the mucosal immune system.
“Direct modulation of the mucosal immune system has been demonstrated by an L. lactis strain that was engineered to produce IL-10 locally in the colon.”
Quote in the paperSubstantial claim0 of 1 sources checked- cites [120] Steidler, L. et al. Treatment of murine colitis by Lactococcus lactis secreting interleukin-10. Science 289, 1352–1355 (2000). source
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- Premisecitation
Early microbial exposure is fundamental in shaping an individual's microbiota.
“Early environmental exposure to microbes is fundamental in shaping an individual’s microbiota.11”
Quote in the paperSubstantial claim0 of 1 sources checked- cites [11] Turnbaugh, P. J. & Gordon, J. I. The core gut microbiome, energy balance and obesity. J. Physiol. 587, 4153–4158 (2009). source
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- Premisecitation
A multicenter randomized double-blind controlled trial of B. animalis DN-173 010 reported improved health-related quality of life in constipation-predominant IBS.
“These findings are supported by a multicenter, randomized, double-blind, controlled trial using Bifidobacterium animalis, strain DN-173 010. This trial reported an improved health-related quality of life score in patients with constipation-predominant IBS.32”
Quote in the paperSubstantial claim0 of 1 sources checked- cites [32] Guyonnet, D. et al. Effect of a fermented milk containing Bifidobacterium animalis DN-173 010 on the health-related quality of life and symptoms in irritable bowel syndrome in adults in primary care: a multicentre, randomized, double-blind, controlled trial. Aliment. Pharmacol. Ther. 26, 475–486 (2007). source
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- Premisecitation
In rodents, the microbiota is easily changed early in life but becomes more resistant to change in adulthood.
“In rodents the microbiota can be easily altered in early life, but becomes more resistant to change in adulthood.12”
Quote in the paperNot a substantial claim0 of 1 sources checked- cites [12] Friswell, M. K. et al. Site and strain-specific variation in gut microbiota profiles and metabolism in experimental mice. PLoS ONE 5, e8584 (2010). source
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- Premisecitation
In twins, lower F. prausnitzii and higher E. coli abundance are associated with an ileal Crohn's disease phenotype.
“A recent study in twins revealed that a reduced abundance of the commensal bacterium Fecalibacterium prausnitzii and an increased abundance of Escherichia coli species was associated with an ileal Crohn’s disease phenotype.”
Quote in the paperNot a substantial claim0 of 1 sources checked- cites [22] Willing, B. et al. Twin studies reveal specific imbalances in the mucosa-associated microbiota of patients with ileal Crohn's disease. Inflamm. Bowel Dis. 15, 653–660 (2009). source
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- Premisecitation
The genetically modified IL-10-producing L. lactis organism was well tolerated in all 10 patients in the phase I trial.
“The genetically modified organism was well tolerated in all 10 patients, but whether this strategy has a beneficial impact on disease activity remains to be determined.”
Quote in the paperNot a substantial claim0 of 1 sources checked- cites [121] Braat, H. et al. A phase I trial with transgenic bacteria expressing interleukin-10 in Crohn's disease. Clin. Gastroenterol. Hepatol. 4, 754–759 (2006). source
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- Premisecitation
A phase I clinical trial administered L. lactis producing human IL-10 to patients with Crohn's disease.
“The potential for designer probiotics to serve as a credible therapeutic approach has been further demonstrated in a phase I clinical trial in patients with Crohn’s disease who were administered a strain of L. lactis that produced human IL-10.121”
Quote in the paperSubstantial claim0 of 1 sources checked- cites [121] Braat, H. et al. A phase I trial with transgenic bacteria expressing interleukin-10 in Crohn's disease. Clin. Gastroenterol. Hepatol. 4, 754–759 (2006). source
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- Premisecitation
These symptom improvements were associated with increased IL-10 production in isolated peripheral blood mononuclear cells in vitro.
“These improvements in clinical symptoms were associated with increased production of the immunomodulatory cytokine interleukin (IL)-IO in isolated peripheral blood mononuclear cells in vitro.29”
Quote in the paperNot a substantial claim0 of 1 sources checked- cites [29] O'Mahony, L. et al. Lactobacillus and Bifidobacterium in irritable bowel syndrome: symptom responses and relationship to cytokine profiles. Gastroenterology 128, 541–551 (2005). source
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- Premisecitation
The IL-10-producing L. lactis strain ameliorates disease in mice with DSS-induced colitis.
“This modified probiotic organism has been shown to ameliorate disease in mice with DSS-induced colitis, and prevent disease development in IL-10−/− mouse.120”
Quote in the paperSubstantial claim0 of 1 sources checked- cites [120] Steidler, L. et al. Treatment of murine colitis by Lactococcus lactis secreting interleukin-10. Science 289, 1352–1355 (2000). source
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- Interpretationnone given
Not every probiotic is helpful in every situation.
“However, not all probiotics are beneficial in all circumstances.”
Quote in the paperSubstantial claim - Premisecitation
The IL-10-producing L. lactis strain prevents disease development in IL-10−/− mice.
“This modified probiotic organism has been shown to ameliorate disease in mice with DSS-induced colitis, and prevent disease development in IL-10−/− mouse.120”
Quote in the paperSubstantial claim0 of 1 sources checked- cites [120] Steidler, L. et al. Treatment of murine colitis by Lactococcus lactis secreting interleukin-10. Science 289, 1352–1355 (2000). source
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- Premisecitation
This dysbiosis correlated more strongly with disease phenotype than with patient genotype.
“This dysbiosis correlated better with disease phenotype than with the genotype of the patient.22”
Quote in the paperNot a substantial claim0 of 1 sources checked- cites [22] Willing, B. et al. Twin studies reveal specific imbalances in the mucosa-associated microbiota of patients with ileal Crohn's disease. Inflamm. Bowel Dis. 15, 653–660 (2009). source
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- Interpretationnone given
Using probiotics to treat IBS remains controversial.
“The use of probiotics for the treatment of patients with IBS remains controversial.”
Quote in the paperNot a substantial claim - Premisecitation
Lower microbial diversity in infancy is associated with a higher risk of atopic disease later in childhood.
“Decreased microbial diversity in infancy seems to be associated with an increased risk of atopic disease later in childhood.14”
Quote in the paperNot a substantial claim0 of 1 sources checked- cites [14] Vael, C. & Desager, K. The importance of the development of the intestinal microbiota in infancy. Curr. Opin. Pediatr. 21, 794–800 (2009). source
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- Premisecitation
In women with IBS, B. infantis 35624 reduced abdominal pain, bloating, bowel dysfunction, incomplete evacuation, straining, and gas compared with placebo after 4 weeks.
“A study in women with IBS revealed that treatment with B. infantis, strain 35624, reduced abdominal pain, bloating, bowel dysfunction, incomplete evacuation, straining, and gas, compared with placebo after 4 weeks of therapy30”
Quote in the paperSubstantial claim0 of 1 sources checked- cites [30] Whorwell, P. J. et al. Efficacy of an encapsulated probiotic Bifidobacterium infantis 35624 in women with irritable bowel syndrome. Am. J. Gastroenterol. 101, 1581–1590 (2006). source
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- Interpretationnone given
Reduced gut microbiome diversity recurs in conditions potentially tied to dysbiosis, including chronic IBD, chronic diarrhea, and necrotizing enterocolitis.
“Decreased diversity of the gut microbiome is a recurring theme in a variety of conditions that are potentially related to dysbiosis, including chronic IBD, chronic diarrhea and necrotizing enterocolitis.”
Quote in the paperNot a substantial claim - Premisecitation
Chronic autoimmune inflammatory diseases such as celiac disease, type 2 diabetes, and obesity are associated with intestinal dysbiosis.
“Chronic autoimmune inflammatory diseases, including celiac disease,17 type 2 diabetes18 and obesity19 are associated with intestinal dysbiosis.”
Quote in the paperNot a substantial claim0 of 3 sources checked- cites [17] De Palma, G. et al. Intestinal dysbiosis and reduced immunoglobulin-coated bacteria associated with coeliac disease in children. BMC Microbiol. 10, 63 (2010). source
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- cites [18] Larsen, N. et al. Gut microbiota in human adults with type 2 diabetes differs from non-diabetic adults. PLoS ONE 5, e9085 (2010). source
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- cites [19] Turnbaugh, P. J. et al. A core gut microbiome in obese and lean twins. Nature 457, 480–484 (2009). source
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- Premisecitation
Levels of these bacteria return toward normal after S. boulardii is given.
“The levels of these bacteria return towards normal values following administration of the yeast probiotic Saccharomyces boulardii.21”
Quote in the paperNot a substantial claim0 of 1 sources checked- cites [21] Swidsinski, A., Loening-Baucke, V., Verstraelen, H., Osowska, S. & Doerffel, Y. Biostructure of fecal microbiota in healthy subjects and patients with chronic idiopathic diarrhea. Gastroenterology 135, 568–579 (2008). source
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- Premisecitation
Rare cases of meningitis have been reported in children who have short bowel syndrome and a central venous catheter and are receiving probiotics.
“For example, bacteremia,127 sepsis128 and meningitis129 have been described on rare occasions in children with short bowel syndrome and a central venous catheter on probiotics.”
Quote in the paperNot a substantial claim0 of 1 sources checked- cites [129] Barton, L. L., Rider, E. D. & Coen, R. W. Bacteremic infection with Pediococcus: vancomycin-resistant opportunist. Pediatrics 107, 775–776 (2001). source
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- Premisecitation
In IL-10−/− mice, a modified L. gasseri carrying a manganese SOD gene from S. thermophilus reduced inflammation after four weeks more than L. gasseri alone.
“After 4 weeks, inflammation was significantly improved in mice treated with this designer probiotic compared to mice treated with L. gasseri alone.125”
Quote in the paperSubstantial claim0 of 1 sources checked- cites [125] Carroll, I. M. et al. Anti-inflammatory properties of Lactobacillus gasseri expressing manganese superoxide dismutase using the interleukin 10-deficient mouse model of colitis. Am. J. Physiol. Gastrointest. Liver Physiol. 293, G729–G738 (2007). source
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- Premisecitation
Rare cases of bacteremia have been reported in children who have short bowel syndrome and a central venous catheter and are receiving probiotics.
“For example, bacteremia,127 sepsis128 and meningitis129 have been described on rare occasions in children with short bowel syndrome and a central venous catheter on probiotics.”
Quote in the paperNot a substantial claim0 of 1 sources checked- cites [127] De Groote, M. A., Frank, D. N., Dowell, E., Glode, M. P. & Pace, N. R. Lactobacillus rhamnosus GG bacteremia associated with probiotic use in a child with short gut syndrome. Pediatr. Infect. Dis. J. 24, 278–280 (2005). source
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- Premisecitation
Those who died in the trial showed signs of necrotizing jejunitis.
“The patients who died had evidence of necrotizing jejunitis.”
Quote in the paperSubstantial claim0 of 1 sources checked- cites [131] Besselink, M. G. et al. Probiotic prophylaxis in predicted severe acute pancreatitis: a randomised, double-blind, placebo-controlled trial. Lancet 371, 651–659 (2008). source
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- Interpretationreasoning
Dependence on exogenous thymidine for growth restricts the organism's ability to spread outside the mammalian host.
“This strategy limits the potential for the organism to spread into the environment beyond the mammalian host.”
Quote in the paperSubstantial claim - Premisecitation
That trial did not lower the rate of infectious complications from acute pancreatitis.
“Although initial animal studies indicated the potential for benefit,130 this clinical trial did not result in a reduced frequency of infectious complications of acute pancreatitis.”
Quote in the paperSubstantial claim0 of 1 sources checked- cites [131] Besselink, M. G. et al. Probiotic prophylaxis in predicted severe acute pancreatitis: a randomised, double-blind, placebo-controlled trial. Lancet 371, 651–659 (2008). source
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- Premisereasoning
So far, no other clinical trial has linked probiotic use to a higher death risk.
“To date, this is the only study to associate probiotic use with an increased risk of death in the setting of a clinical trial.”
Quote in the paperSubstantial claim - Premisecitation
In that pancreatitis trial, the group given the probiotic had a significantly higher death risk.
“Moreover, a significantly increased risk of death was reported in the population receiving the probiotic formulation.131”
Quote in the paperSubstantial claim0 of 1 sources checked- cites [131] Besselink, M. G. et al. Probiotic prophylaxis in predicted severe acute pancreatitis: a randomised, double-blind, placebo-controlled trial. Lancet 371, 651–659 (2008). source
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- Interpretationcitation
For some groups of patients, probiotics might be inadvisable.
“Although generally considered safe, some studies have highlighted that probiotics may be ill advised in specific patient populations.”
Quote in the paperSubstantial claim - Premisecitation
In vitro, among three Lactobacillus strains, L. paracasei stimulated dendritic cells least, compared with L. plantarum and LGG.
“For example, testing three different Lactobacillus strains in vitro indicated that L. paracasei has the least stimulatory effects on dendritic cells compared with L. plantarum and LGG.25”
Quote in the paperSubstantial claim0 of 1 sources checked- cites [25] Mileti, E., Matteoli, G., Iliev, I. D. & Rescigno, M. Comparison of the immunomodulatory properties of three probiotic strains of Lactobacilli using complex culture systems: prediction for in vivo efficacy. PLoS ONE 4, e7056 (2009). source
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- Premisecitation
Preclinical assessment of a microorganism's probiotic potential covers antibiotic resistance, safety, and possible efficacy.
“Testing for the probiotic potential of various microorganisms starts at the preclinical level and includes evaluations of antibiotic resistance, safety and potential efficacy132”
Quote in the paperNot a substantial claim0 of 1 sources checked- cites [132] Sorokulova, I. Preclinical testing in the development of probiotics: a regulatory perspective with Bacillus strains as an example. Clin. Infect. Dis. 46 (Suppl. 2), S92–S95 (2008). source
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- Premisecitation
The recombinant TFF-producing L. lactis reduces DSS-induced disease in mice.
“Instead of traditional orogastric administration of TFF, which sticks to the mucus layer in the small bowel preventing its localization in the colon, use of the recombinant bacterium enables delivery of TFF directly to the colonic mucosa and results in amelioration of DSS-induced disease in mice.123”
Quote in the paperSubstantial claim0 of 1 sources checked- cites [123] Vandenbroucke, K. et al. Active delivery of trefoil factors by genetically modified Lactococcus lactis prevents and heals acute colitis in mice. Gastroenterology 127, 502–513 (2004). source
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- Premisecitation
Trefoil factors have been studied in animal models of gastric ulcers, colitis, and necrotizing enterocolitis.
“TFFs are cytoprotective compounds that promote wound healing in the intestinal tract and have been used in models of gastric ulceration, colitis and necrotizing enterocolitis.122”
Quote in the paperNot a substantial claim0 of 1 sources checked- cites [122] Sturm, A. & Dignass, A. U. Epithelial restitution and wound healing in inflammatory bowel disease. World J. Gastroenterol. 14, 348–353 (2008). source
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- Interpretationreasoning
Collectively, the cited work points to possible benefits from designer probiotics.
“Taken together, these studies highlight the potential beneficial effects of designer probiotics.”
Quote in the paperSubstantial claim - Premisecitation
Rare cases of sepsis have been reported in children who have short bowel syndrome and a central venous catheter and are receiving probiotics.
“For example, bacteremia,127 sepsis128 and meningitis129 have been described on rare occasions in children with short bowel syndrome and a central venous catheter on probiotics.”
Quote in the paperNot a substantial claim0 of 1 sources checked- cites [128] Land, M. H. et al. Lactobacillus sepsis associated with probiotic therapy. Pediatrics 115, 178–181 (2005). source
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- Premisecitation
A trial examined a six-bacteria probiotic mixture given into the duodenum of intensive-care patients with severe pancreatitis.
“A study has tested the safety and efficacy of intra-duodenal administration of a probiotic mixture of six bacteria in patients with severe pancreatitis who were cared for in an intensive care unit setting.”
Quote in the paperSubstantial claim0 of 1 sources checked- cites [131] Besselink, M. G. et al. Probiotic prophylaxis in predicted severe acute pancreatitis: a randomised, double-blind, placebo-controlled trial. Lancet 371, 651–659 (2008). source
Not checked in the free run.
- Interpretationreasoning
Such patients face a higher risk that organisms, including probiotic bacteria and fungi, cross into the bloodstream.
“These individuals are at increased risk of translocation of organisms, including viable bacteria and fungi strains that are employed in the clinical setting as probiotics.”
Quote in the paperSubstantial claim - Premisecitation
In IBD patients, mucosal biopsies show an imbalance between reactive oxygen species and antioxidant micronutrients, including lower superoxide dismutase.
“Biopsy specimens obtained from patients with IBD have been shown to have imbalances in the formation of reactive oxygen species (ROS) and antioxidant micronutrients, with decreases in the ROS-neutralizing enzyme superoxide dismutase (SOD).”
Quote in the paperSubstantial claim0 of 1 sources checked- cites [124] Lih-Brody, L. et al. Increased oxidative stress and decreased antioxidant defenses in mucosa of inflammatory bowel disease. Dig. Dis. Sci. 41, 2078–2086 (1996). source
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- Premisecitation
A recombinant bacterium that produces TFF can deliver the factor straight to the colonic mucosa.
“Instead of traditional orogastric administration of TFF, which sticks to the mucus layer in the small bowel preventing its localization in the colon, use of the recombinant bacterium enables delivery of TFF directly to the colonic mucosa and results in amelioration of DSS-induced disease in mice.123”
Quote in the paperSubstantial claim0 of 1 sources checked- cites [123] Vandenbroucke, K. et al. Active delivery of trefoil factors by genetically modified Lactococcus lactis prevents and heals acute colitis in mice. Gastroenterology 127, 502–513 (2004). source
Not checked in the free run.
- May combine two claims. 15
- Classified as probably not a substantial claim. 5
- The quote only partly states this claim. 1
May combine two claims.
PremisecitationA mutually beneficial relationship between helpful symbionts and commensals is needed for health, and disturbing this balance causes dysbiosis and clinical disease.
“A mutualistic relationship between beneficial symbionts and commensals is important for the maintenance of health and wellbeing; alterations in this balance leads to dysbiosis and ultimately clinical disease expression.1”
Quote in the paperSubstantial claim0 of 1 sources checked- cites [1] Round, J. L. & Mazmanian, S. K. The gut microbiota shapes intestinal immune responses during health and disease. Nat. Rev. Immunol. 9, 313–323 (2009). source
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May combine two claims.
PremisecitationVaginal delivery is linked to greater intestinal colonization by bifidobacteria, but not lactobacilli, than caesarean delivery.
“For example, increased intestinal colonization with bifidobacteria, but not lactobacilli, is associated with vaginal births compared with caesarean section deliveries.6”
Quote in the paperNot a substantial claim0 of 1 sources checked- cites [6] Chen, J., Cai, W. & Feng, Y. Development of intestinal bifidobacteria and lactobacilli in breast-fed neonates. Clin. Nutr. 26, 559–566 (2007). source
Not checked in the free run.
May combine two claims.
InterpretationreasoningDelivery route and early feeding patterns affect intestinal colonization.
“Therefore, route of delivery and early life feeding patterns have an influence on intestinal colonization.”
Quote in the paperSubstantial claimMay combine two claims.
InterpretationcitationSeveral proposed mechanisms explain probiotics' reported benefits in intestinal disease, and they vary by strain and disease model.
“Multiple different putative mechanisms for the reported beneficial effect of probiotics in intestinal disease exist. These mechanisms differ according to the specific strain of probiotic organism and disease model tested”
Quote in the paperNot a substantial claim0 of 1 sources checked- cites [26] Sherman, P. M., Ossa, J. C. & Johnson-Henry, K. Unraveling mechanisms of action of probiotics. Nutr. Clin. Pract. 24, 10–14 (2009). source
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May combine two claims.
PremisecitationDysbiosis is associated with protracted diarrhea and reduced F. prausnitzii and Bacteroides.
“Dysbiosis has been shown to be associated with protracted diarrhea resulting in a reduction in F. prausnitzii and Bacteroides in such patients.21”
Quote in the paperNot a substantial claim0 of 1 sources checked- cites [21] Swidsinski, A., Loening-Baucke, V., Verstraelen, H., Osowska, S. & Doerffel, Y. Biostructure of fecal microbiota in healthy subjects and patients with chronic idiopathic diarrhea. Gastroenterology 135, 568–579 (2008). source
Not checked in the free run.
May combine two claims.
PremisecitationIn constipation-predominant IBS, B. lactis DN-173-010 produced less abdominal distension and increased colonic transit times compared with placebo.
“Patients with constipation-predominant IBS who received this probiotic demonstrated less abdominal distension and increased colonic transit times compared with patients who received placebo.31”
Quote in the paperSubstantial claim0 of 1 sources checked- cites [31] Agrawal, A. et al. Clinical trial: the effects of a fermented milk product containing Bifidobacterium lactis DN-173-010 on abdominal distension and gastrointestinal transit in irritable bowel syndrome with constipation. Aliment. Pharmacol. Ther. 29, 104–114 (2008). source
Not checked in the free run.
Probably not a substantial claim: may not pass S3 (load-bearing), S4 (based).
Interpretationnone givenOrganisms can act differently when given in combinations than when given alone.
“Organisms may behave differently when administered in combinations than in isolation.”
Quote in the paperNot a substantial claimProbably not a substantial claim: may not pass S3 (load-bearing).
PremisecitationThe appropriateness of study designs has been criticized.
“However, it is important to acknowledge that the appropriateness of the design of studies has been criticized.34”
Quote in the paperNot a substantial claim0 of 1 sources checked- cites [34] Brenner, D. M., Moeller, M. J., Chey, W. D. & Schoenfeld, P. S. The utility of probiotics in the treatment of irritable bowel syndrome: a systematic review. Am. J. Gastroenterol. 104, 1033–1049 (2009). source
Not checked in the free run.
May combine two claims.
InterpretationreasoningEarly exposure to certain bacteria and changes in gut microbiome diversity can strongly affect health across life.
“Therefore, exposure to certain bacteria in early life and changes in the diversity of the gut microbiome can have a profound effect on health and wellbeing throughout an individual’s life.”
Quote in the paperSubstantial claimMay combine two claims.
PremisecitationIn IBS patients, B. infantis 35624, but not L. salivarius UCC4331, improved quality of life and reduced abdominal pain and bloating without changing stool consistency.
“Patients with IBS treated with Bifidobacterium infantis, strain 35624, but not Lactobacillus salivarius, strain UCC4331, reported improved quality of life and reduced abdominal pain and bloating in the absence of changes in stool consistency.”
Quote in the paperSubstantial claim0 of 1 sources checked- cites [29] O'Mahony, L. et al. Lactobacillus and Bifidobacterium in irritable bowel syndrome: symptom responses and relationship to cytokine profiles. Gastroenterology 128, 541–551 (2005). source
Not checked in the free run.
Probably not a substantial claim: may not pass S3 (load-bearing).
PremisecitationA previous study found that Crohn's-disease-associated ulceration was not linked to dysbiosis.
“This finding is in contrast with a previous study, which found that Crohn’s-disease-associated ulceration was not linked to dysbiosis.23”
Quote in the paperNot a substantial claim0 of 1 sources checked- cites [23] Seksik, P. et al. Search for localized dysbiosis in Crohn's disease ulcerations by temporal temperature gradient gel electrophoresis of 16S rRNA. J. Clin. Microbiol. 43, 4654–4658 (2005). source
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May combine two claims.
PremisecitationIBS is associated with increased intestinal permeability, altered motility, visceral hypersensitivity, altered bacterial colonization, and extraintestinal anxiety and depression.
“IBS is associated with increased intestinal permeability, altered motility, visceral hypersensitivity, altered bacterial colonization, as well as extraintestinal manifestations, including concomitant anxiety and depression.27”
Quote in the paperNot a substantial claim0 of 1 sources checked- cites [27] Ford, A. C., Talley, N. J., Schoenfeld, P. S., Quigley, E. M. & Moayyedi, P. Efficacy of antidepressants and psychological therapies in irritable bowel syndrome: systematic review and meta-analysis. Gut 58, 367–378 (2009). source
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May combine two claims.
PremisecitationIBD, especially Crohn's disease, and chronic diarrhea are associated with altered microbial composition of the large bowel.
“IBD, in particular Crohn’s disease,20 and chronic diarrhea21 are conditions among those recognized to be associated with an altered microbial composition of the large bowel.”
Quote in the paperSubstantial claim0 of 2 sources checked- cites [20] Tannock, G. W. Molecular analysis of the intestinal microflora in IBD. Mucosal Immunol. 1 (Suppl. 1), S15–S18 (2008). source
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- cites [21] Swidsinski, A., Loening-Baucke, V., Verstraelen, H., Osowska, S. & Doerffel, Y. Biostructure of fecal microbiota in healthy subjects and patients with chronic idiopathic diarrhea. Gastroenterology 135, 568–579 (2008). source
Not checked in the free run.
Probably not a substantial claim: may not pass S3 (load-bearing). May combine two claims.
Interpretationnone givenPoor identification of probiotic strains in the literature blocks verification of published studies and hinders investigators and the public.
“The inadequate identification in the literature of probiotic strains prevents the verification of published studies and continues to be an obstacle to both investigators and the general population.”
Quote in the paperNot a substantial claimMay combine two claims.
PremisecitationMany animal and human studies find that some probiotic strains lessen disease severity while others do not.
“Numerous studies, both in animal models and in human clinical trials, report success in reducing the severity of a number of diseases by use of certain probiotic strains, but not by use of others.”
Quote in the paperSubstantial claimMay combine two claims.
InterpretationreasoningEvidence is accumulating that probiotics may help prevent and treat several human diseases, but only particular organisms are likely to work for particular conditions.
“There is a growing body of evidence to support the potential use of probiotics in the prevention and treatment of various human diseases, the caveat being that only specific organisms may be effective for certain disease manifestations.”
Quote in the paperSubstantial claimMay combine two claims.
PremisecitationWhen TFF is given by the traditional orogastric route, it adheres to small-bowel mucus and does not reach the colon.
“Instead of traditional orogastric administration of TFF, which sticks to the mucus layer in the small bowel preventing its localization in the colon, use of the recombinant bacterium enables delivery of TFF directly to the colonic mucosa and results in amelioration of DSS-induced disease in mice.123”
Quote in the paperSubstantial claim0 of 1 sources checked- cites [123] Vandenbroucke, K. et al. Active delivery of trefoil factors by genetically modified Lactococcus lactis prevents and heals acute colitis in mice. Gastroenterology 127, 502–513 (2004). source
Not checked in the free run.
Classified as probably not a substantial claim.
PremisecitationThose results prompted a test of L. paracasei in mice with DSS-induced colitis.
“These findings led to testing of the L. paracasei strain in mice with DSS-induced colitis.25”
Quote in the paperSubstantial claim0 of 1 sources checked- cites [25] Mileti, E., Matteoli, G., Iliev, I. D. & Rescigno, M. Comparison of the immunomodulatory properties of three probiotic strains of Lactobacilli using complex culture systems: prediction for in vivo efficacy. PLoS ONE 4, e7056 (2009). source
Not checked in the free run.
May combine two claims.
PremisecitationTrefoil factors are cytoprotective substances that aid wound healing in the gut.
“TFFs are cytoprotective compounds that promote wound healing in the intestinal tract and have been used in models of gastric ulceration, colitis and necrotizing enterocolitis.122”
Quote in the paperSubstantial claim0 of 1 sources checked- cites [122] Sturm, A. & Dignass, A. U. Epithelial restitution and wound healing in inflammatory bowel disease. World J. Gastroenterol. 14, 348–353 (2008). source
Not checked in the free run.
The quote only partly states this claim.
PremisecitationA modified Bacteroides ovatus strain BOV975 that releases human keratinocyte growth factor 2 when exposed to dietary xylan lessened colitis in a DSS mouse model of IBD.
“This recombinant organism improved colitis in a DSS-induced mouse model of IBD.126”
Quote in the paperSubstantial claim0 of 1 sources checked- cites [126] Hamady, Z. Z. et al. Xylan-regulated delivery of human keratinocyte growth factor-2 to the inflamed colon by the human anaerobic commensal bacterium Bacteroides ovatus. Gut 59, 461–469 (2010). source
Not checked in the free run.
The paper relies on this without support.
Maintaining the gut epithelial barrier is important for stopping luminal antigens from entering the body and systemic circulation.
“Maintenance of gut epithelial barrier function is important to prevent luminal antigens from entering the body and systemic circulation.”
The paper relies on this without support.
The intestinal tract is the largest reservoir of microbes in the human body.
“Given that the intestinal tract is the largest reservoir of microbes in the human body, it is not surprising that the use of probiotic organisms in disease has been investigated extensively in intestinal disorders”
Claims other papers make about this one
Each is checked against this paper’s own text: does it say what the citing paper says it does?
In a normal physiological state, beneficial and pathogenic bacteria are balanced; probiotics account for the majority and can compete with harmful bacteria for nutrients.
“In a normal physiological state, beneficial and pathogenic bacteria are balanced; probiotics account for the majority and can compete with harmful bacteria for nutrients (Gareau, Sherman & Walker, 2010).”
From The modulatory effects of gut microbes and metabolites on blood-brain barrier integrity and brain function in sepsis-associated encephalopathy (2023) · cites this paper as Gareau, Sherman & Walker, 2010
Most indications of a microbiota-gut-brain axis in humans have come from patients with gastrointestinal disorders.
“Most indications of a ‘microbiota-gut-brain axis’ in humans have come from patients with gastrointestinal disorders (Brenner et al. 2009; Gareau et al. 2010; Kennedy et al. 2012).”
From Prebiotic intake reduces the waking cortisol response and alters emotional bias in healthy volunteers (2015) · cites this paper as Gareau et al. 2010
Probiotic bacteria, particularly Lactobacillus and Bifidobacterium species, are known to modify GI microbiota and reduce GI episode severity and respiratory tract infections associated with training.
“Probiotic bacteria, particularly the gram-positive genera Lactobacillus and Bifidobacterium species, are known to modify GI microbiota [17,18,19], and have been shown to reduce GI episode severity [20] and respiratory tract infections commonly associated with training [21].”
Self-check
Percentages, sums and reported differences re-computed from the paper’s own numbers.
Each contradiction between two passages listed here was confirmed by an independent check.
LGG is assigned to two different species
MinorThe text identifies LGG as Lactobacillus rhamnosus GG elsewhere, but here calls it a strain of L. helveticus.
“L. helveticus, strains R0052 and LGG both prevent EHEC-induced increases in epithelial permeability”
“L. rhamnosus GG (LGG)”
The third cited meta-analysis is described as a different type of study
MinorThe text groups reference 86 with meta-analyses of necrotizing enterocolitis and mortality. The cited reference is titled as a study of growth and neurodevelopmental outcomes, not as a meta-analysis of those outcomes.
“Three meta-analyses84–86 indicate that probiotic supplementation in preterm infants significantly reduces the incidence of both severe necrotizing enterocolitis and mortality”
“86. Chou IC Lack of effects of oral probiotics on growth and neurodevelopmental outcomes in preterm very low birth weight infants J. Pediatr 2010 156 393 396 19914635 10.1016/j.jpeds.2009.09.051”
No citation lists for this paper
No citation lists for this paper yet — checked again daily.
References 132 · Cited by 907
- Authors
- Gareau, M. G., Sherman, P. M., & Walker, W. A.
- Affiliations
- University of Toronto (CA)
- Harvard University (US)
- Corresponding author
- Sherman, Philip M.
- Venue
- Nature Reviews Gastroenterology & Hepatology
- Published
- 2010-07-27
- Volume
- 7
- Issue
- 9
- Pages
- 503-514
- ISSN
- 1759-5045 (ISSN-L)
- 1759-5053
- PMC
- PMC4748966
- OpenAlex
- W2018359273
- Cited by
- 907
- References
- 132
- Citations by year
- 2026: 36 · 2025: 66 · 2024: 57 · 2023: 59 · 2022: 102 · 2021: 62 · 2020: 84 · 2019: 63 · 2018: 67 · 2017: 44 · 2016: 54 · 2015: 39 · 2014: 44 · 2013: 53 · 2012: 41
- FWCI
- 4.97
- Type
- journal article
- Language
- en
- Open access
- green
- www.ncbi.nlm.nih.gov
- Locations
- Nature Reviews Gastroenterology & Hepatology (publishedVersion)
- PubMed (publishedVersion)
- PubMed Central (acceptedVersion)
- Funders
- Canadian Institutes of Health Research
- National Institute of Diabetes and Digestive and Kidney Diseases (P01DK033506, R01DK070260, P30DK040561)
- Eunice Kennedy Shriver National Institute of Child Health and Human Development (R01HD012437)
- 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 › Medicine › Gastroenterology › Gastrointestinal motility and disorders
- Keywords
- probiotics, gut microbiota, gut health, intestinal disorders, probiotic mechanisms of action
- MeSH terms
- Diarrhea, Gastrointestinal Diseases, Humans, Inflammatory Bowel Diseases, Probiotics, Gastrointestinal Tract
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Registry, retraction, Cites and statistics results are computed, not judged, with one exception: a printed reference that no index lists is read once by a model before it counts as a citation error. Claims are extracted by a model and kept only when their quote appears verbatim in the text; each cited source is then checked, with a model’s help, for whether it says what the claim relies on. Those verdicts can be wrong — read the claim’s quote and the cited source before relying on one.
Claims read by deepseek-v4.1-flash under definition version 3 (extract-v3) on 2026-10-06.
Classified by jev-1.13-20260917 (gold-guideline-v0.2) on 2026-10-06.
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