Probiotics (living agents) & Ulcerative Colitis (UC)

Why are probiotics considered for the treatment of ulcerative colitis?

Ulcerative colitis is an inflammatory condition that affects the colon, with an annual incidence rate of about 10 to 20 cases per 100,000 people. Most individuals with ulcerative colitis can achieve remission, but there remains a group that does not respond to first- or second-line therapies. A significant number of people experience adverse effects from current treatments. As a result, there is a continuous search for new alternatives in the treatment of ulcerative colitis. Probiotics, which are live microbial feed supplements, may offer benefits to the host by improving intestinal microbial balance, enhancing gut barrier function, and boosting the local immune response (1). Probiotics, such as Lactobacillus, Bifidobacterium, and E. coli Nissle, play a crucial role in maintaining gut health. They compete for adhesion sites, which helps in preventing harmful bacteria from taking hold. Additionally, they enhance the barrier function of the gut lining, making it more robust against potential threats. Probiotics also have the ability to reduce pro-inflammatory cytokines like Tumor Necrosis Factor alfa (TNF-alfa) and Interleukin-1 (IL-1) / Interleukin-1 family, which are often associated with inflammation. Furthermore, they boost the production of Interleukin-10 (IL-10), an anti-inflammatory cytokine, through the activation of the PI3K/Akt and NFKB pathways (7). Escherichia coli Nissle 1917 demonstrated strong evidence for maintenance treatment of UC in remission. Bifidobacterium and VSL#3 showed strong evidence for inducing remission in patients with mild to moderately active UC (17). Several probiotic strains, such as Bifidobacterium longum and Lactobacillus rhamnosus, have been approved as oral supplements for the treatment of ulcerative colitis (UC) in clinical trials (7, 8). However, there is still no consensus that probiotics perform better than a placebo (9). Probotics are a potential treatment modality for ulcerative colitis (UC), but their efficacy is often compromised by gastrointestinal disease (2, 3).

What systematic reviews and meta-analyses focus on the use of probiotics in ulcerative colitis?

• Estevinho et al. 2024 United European Gastroenterol J 12(7): 960-981 (18)


• Lorentz & Müller 2022 J Gastrointestin Liver Dis 31(1): 74-84 (19)


• Iheozor-Ejiofor et al. 2020 Cochrane Database Syst Rev 3: Cd007443 (1)


• Kaur et al. 2020 Cochrane Database of Systematic Reviews 10.1002/14651858.CD005573.pub3 (4)


• Astó et al. 2019 Nutrients 11(2): 293 (5)


• Ghouri et al. 2014 Clin Exp Gastroenterol. 7: 473-87 (6)

What forms of therapeutic management of ulcerative colitis need to be distinguished?

Induction therapy for active UC and maintenance therapy for UC in remission

What is the significance of prebiotics in maintaining clinical remission of Ulcerative Colitis (UC) according to systematic reviews and meta-analyses?

As of September 2023: According to a meta-analysis of 32 randomized, clinical trials involving 3225 participants, participants treated with probiotics showed higher odds of remission versus control, with OR 2.00 and 95% CI 1.28–3.11, and a trend toward reduced clinical recurrence in inactive UC, with OR 0.65 and 95% CI 0.42-1.01). Multi-strain formulations are superior for UC remission and recurrence prevention. However, overall certainty of evidence is low (18).

As of June 2021: According to a systematic review of 16 randomized, clinical trials involving 1638 participants, participants treated with probiotics showed a possibly beneficial role as an adjunct to standard therapy in active UC, whereas evidence remains inconclusive for placebo-controlled maintenance therapy in inactive UC (19).

As of October 2019: The Cochrane review (CD007443) focusing on Maintenance Therapy for UC in Remission included 12 studies involving 1,473 randomized participants who met the inclusion criteria. The majority of participants were adults, with an average age ranging from 32 to 51 years, and an overall age range of 18 to 88 years.

• The evidence does not clearly indicate whether there is a difference in the occurrence of clinical relapse when comparing probiotics to a placebo.


• When comparing probiotics with 5-ASA, the evidence suggests there may be little or no difference in clinical relapse, with a relative risk (RR) of 1.01 and a 95% confidence interval (CI) ranging from 0.84 to 1.22, based on two studies involving 452 participants.


• When probiotics combined with 5-ASA are compared to 5-ASA alone, it remains uncertain if there is any difference in clinical relapse.
  The effectiveness of probiotics in maintaining remission for individuals with ulcerative colitis is still uncertain. This uncertainty arises from evidence that is of low to very low certainty, primarily due to poorly conducted studies that provide limited data from a small number of participants. Future research should focus on comparing probiotics with 5-ASA instead of a placebo, as this would more accurately represent the standard care provided to those with ulcerative colitis. It is essential to conduct studies that are appropriately powered and have a minimum duration of 12 months (1).

As of late 2013: A systematic review that examined 21 trials involving patients with ulcerative colitis (UC) found evidence suggesting that probiotics can be beneficial for both inducing and maintaining remission in UC. However, further high-quality studies are necessary to determine whether probiotics have a definitive role in the induction or maintenance of remission in UC (6).

What is the significance of probiotics in inducing clinical remission of Ulcerative Colitis (UC) according to systematic reviews and meta-analyses?

As of September 2023: According to a meta-analysis of 32 randomized, clinical trials involving 3225 participants, participants treated with probiotics showed higher odds of remission versus control, with OR 2.00 and 95% CI 1.28–3.11, and a trend toward reduced clinical recurrence in inactive UC, with OR 0.65 and 95% CI 0.42-1.01). Multi-strain formulations are superior for UC remission and recurrence prevention. However, overall certainty of evidence is low (18).

As of October 2019: The Cochrane review (CD005573) focusing on Induction therapy for active UC included 14 studies involving 865 randomized participants who met the inclusion criteria. The majority of participants were adults, with an average age ranging from 12.5 to 47.7 years.

• Probiotics have the potential to induce clinical remission when compared to a placebo, with a relative risk (RR) of 1.73 and a 95% confidence interval (CI) ranging from 1.19 to 2.54.


• The induction of remission with probiotics may show little or no difference when compared to 5-ASA, as indicated by a relative risk (RR) of 0.92 and a 95% confidence interval (CI) ranging from 0.73 to 1.16, based on one study involving 116 participants.


• A single study with low-certainty evidence suggests that probiotics, when used in conjunction with 5-ASA, might slightly enhance the induction of remission as measured by the Sunderland disease activity index, compared to using 5-ASA alone.
  The available evidence, though of low certainty, indicates that probiotics might help achieve clinical remission in individuals with active ulcerative colitis when compared to a placebo. However, when probiotics are used alone, they may not significantly differ in effectiveness from 5-ASA in inducing clinical remission. A single study, which did not clearly define remission, suggests that probiotics could slightly enhance the induction of remission when combined with 5-ASA. There is a lack of evidence regarding the effectiveness of probiotics in individuals with severe and more extensive forms of the disease, and it remains unclear if certain probiotic preparations are more effective than others. To fill these gaps in the evidence, further targeted and well-designed randomized controlled trials (RCTs) are necessary. These studies should be appropriately powered and should employ standardized participant groups and outcome measures consistent with the broader field, along with reporting practices that minimize the risk of bias (4).

As of late 2018: The meta-analysis of the 12 trials included in the study indicates that probiotics appear to be beneficial for achieving remission in patients with ulcerative colitis (UC). However, this benefit is heavily influenced by the specific UC scale used. Notably, a significant effect is only observed when using the UCDAI and DAI scales, which are the scales recommended by the FDA for UC clinical trials involving pharmaceuticals. Other scales do not show this effect. Additionally, the composition of the probiotics seems to be important, with those containing bifidobacteria appearing to be the most advantageous (5).

As of late 2013: A systematic review that examined 21 trials involving patients with ulcerative colitis (UC) found evidence suggesting that probiotics can be beneficial for both inducing and maintaining remission in UC. However, further high-quality studies are necessary to determine whether probiotics have a definitive role in the induction or maintenance of remission in UC (6).

What are the probiotics studied for their influence on maintaining remission of Ulcerative Colitis (UC)?

Bifidobacterium breve strain Yakult + Lactobacillus acidophilus had no effect on time to relapse in Ulcerative colitis (UC) patients compared with placebo (20).

Escherichia coli Nissle 1917 / E. coli Nissle 1917 is as effective as mesalazine for preventing relapse in Ulcerative Colitis (UC) in remission (21, 22, 23).

A high-potency probiotic medical food containing 8 different strains, called VSL#3 TM, induces remission and relieves relapse in mild to moderate active Ulcerative Colitis (UC) (27)

What are the probiotics successfully studied for their influence on inducing clinical remission of Ulcerative Colitis (UC)?

Escherichia coli Nissle 1917 / E. coli Nissle 1917 is not clearly superior to placebo for induction of remission (21, 22, 23). Other probiotics as Bifidobacterium (10) and Lactobacillus (11) seem to have beneficial effects in managing active Ulcerative Colitis (UC) (12).

Lacticaseibacillus rhamnosus can induce remission in patients with mild to moderate ulcerative colitis (25).

MH002 treatment was both safe and well tolerated. It led to significant improvements in disease activity and inflammatory parameters. Consequently, MH002 emerges as a promising new treatment option for patients with mild to moderate ulcerative colitis (UC) who do not achieve sufficient control with 5-aminosalicylic acid (5ASA). However, further Phase II and III studies are needed to confirm these data (26).

A high-potency probiotic medical food containing 8 different strains, called VSL#3 TM, induces remission and relieves relapse in mild to moderate active Ulcerative Colitis (UC) (27)

Different results were observed in Ulcerative Colitis (UC), where adding a probiotic to conventional treatment improved induction and maintenance remission in mild to moderate active Ulcerative Colitis (UC) (6).

Limited clinical investigations using Escherichia coli Nissle 1917 have demonstrated that probiotic-based therapeutic applications can be efficacious in patients with chronic Ulcerative Colitis (UC) and irritable bowel syndrome (13, 14, 15)

References

(1) Iheozor-Ejiofor et al. 2020 Cochrane Database Syst Rev 3: Cd007443
(2) Hu et al. 2021c Front. Med. 8: 766126
(3) Guo et al. 2024 Cell Host & Microbe 32: 1502-1518
(4) Kaur et al. 2020 Cochrane Database of Systematic Reviews 10.1002/14651858.CD005573.pub3
(5) Astó et al. 2019 Nutrients 11(2): 293
(6) Ghouri et al. 2014 Clin Exp Gastroenterol. 7: 473-87
(7) Shen et al. 2018 World J Gastroenterol 24: 5-14
(8) Koretz 2018 Am J Gastroenterol 113: 1125-1136
(9) Suez et al. 2019 Nat. Med. 25: 716
(10) Kato et al. 2004 Aliment Pharmacol Ther. 20(10): 1133-41
(11) Oliva et al. 2012 Aliment Pharmacol Ther. 35(3): 327-34
(12) Ortigão et al. 2020
(13) Plassmann & Schulte-Witte 2007 Med. Klin. 102: 888-892
(14) Henker et al. 2008 Z. Gastroenterol. 46: 874-875
(15) Matthes et al. 2010a BMC Complement. Altern. Med. 10: 1-8
(16) Mallon et al. 2007 Cochrane Database Syst Rev doi: 10.1002/14651858.CD005573.pub2.
(17) Ma et al. 2024 Open Life Sciences 19(1): 20220821
(18) Estevinho et al. 2024 United European Gastroenterol J 12(7): 960-981
(19) Lorentz & Müller 2022 J Gastrointestin Liver Dis 31(1): 74-84
(20) Matsuoka et al. 2018 Dig Dis Sci 63(7): 1910-1919
(21) Scaldaferri et al. 2016 World J Gastroenterol 22(24): 5505-5511
(22) Kim et al. 2021a Int J Mol Sci 22: 2122
(23) Losurdo et al. 2015 J Gastrointestin Liver Dis 24(4):499-505
(24) Naseer et al. 2020 Curr Clin Pharmacol 15(3): 216-233
(25) Pagnini et al. 2023 Microorganisms 11(6): 1381
(26) Vermeire et al. 2024 Journal of Crohn's and Colitis 18(suppl.1): i1243-i1244
(27) Sood et al. 2009

see also:
Gut microbiota & Ulcerative colitis (UC)
Microbial Ecosystem Therapeutics 2 (MET-2) & Ulcerative colitis (UC)
Nutritonal Therapy & Ulcerative colitis (UC)
Probiotics (living agents) & Crohn’s Disease (CD)
Probiotics (living agents) & Inflammatory Bowel Disease (IBD)
Probiotics (living agents) & Irritable Bowel Syndrome (IBS)
Probiotics (living agents) & Non-Alcoholic Fatty Liver Disease (NAFLD) / Metabolic dysfunction-associated fatty liver disease (MAFLD)
Ulcerative colitis (UC) & Drugs/Treatments

Some studies show that certain probiotics, like lactobacillus and Escherichia coli Nissle 1917, might help with ulcerative colitis and prevent pouchitis relapse (24)