CIn 1953, when the German Scientist Werner Kollath was introduced the term probiotics by which to mean “active substances essential for a healthy life” (11) and then after various scientist and researchers across the Globe have been explored the beneficial characteristics of probiotic human strains. Many nutritionists and health specialists have been reported that the probiotics can offer many health benefits when administered in adequate amount with sufficient potency. Each probiotic strains have their own specific beneficial characteristics to provide health benefits to the host in a particular health problem.

In last two decades, it is found that there was an explosion of interest in probiotics, with an annual number of randomized controlled trials (RCTs) ranging between 144 and 194; in 2017, there were also 49 meta-analyses (12). In both animal trials and human trials, probiotics have been investigated to determine potential beneficial effects in the prevention and treatment of a wide variety of systemic conditions. These conditions include rebalancing the population of bacteria in the gut, aiding digestion, inflammatory and autoimmune diseases such as rheumatoid arthritis, ulcerative colitis, multiple sclerosis, and hepatic encephalopathy (12).

The advantages of probiotics also include the regulation of immune system function, which is often dependent on the human strain of probiotic bacteria (9). Modulation of the immune system and anti-inflammatory effects are among the beneficial effects of probiotics (9).

Immunodeficiency and inflammatory are the common health problems which effect the major population of the world. Even an estimated 3.1 million adults (1.3%) in the United States have been diagnosed with inflammatory bowel disease (IBD), which includes Crohn’s disease and ulcerative colitis (14). Human probiotic strain manufacturer in USA are focused on the development and manufacturing of new potential probiotic strains. Many companies in USA, manufacturing different human probiotic strains which includes Bacillus subtilis DEIII, Lactobacillus acidophilus, Lactobacillus plantarum, Lacticaseibacillus casei, Lactiplantibacillus plantarum, Lacticaseibacillus paracasei, Levilactobacillus breve, Lactococcus lactis, Enterococcus fecium, Bifidobacterium bifidum, Lactobacillus reuteri-DSM17938, Bifidobacterium longum, Lactobacillus rhmnosus GG and many more.

Probiotics, as anti-inflammatory agents, could have beneficial effects on modulating signalling pathways and thus improve the inflammatory status in patients with IBD. Levilactobacillus brevis is another Lactobacillus strain with remarkable effects on intestinal homeostasis and inhibitory effects on intestinal inflammation (6). Probiotics not only have an anti-inflammatory effect but often continue to act for up to 3 weeks after the end of treatment and therefore appear to be a suitable means of prolonging the duration of remission and controlling symptoms in patients with IBD (8).

Various probiotic strains for inflammatory problems have been explored and reported through experimental and clinical trials. It was proven by various scientist that selective strains of probiotics like Bifidobacterium bifidum, Ruminococcus obeum, Blautia coccoides, and Lacticaseibacillus casei strain Shirota can reduce inflammation and restore tolerance in SLE animal models (10).

Dr.Luis Fontana was reported that administration of Lacticaseibacillus paracasei CNCM I-4034, Bifidobacterium breve CNCM I-4035 and Lacticaseibacillus rhamnosus CNCM I-4036 may down regulate gut inflammatory genes in obese rats. In addition, numerous studies have publicized that the use of probiotics could improve immune/inflammatory processes in some diseases such as type 2 diabetes, inflammatory bowel disease (IBD) and neuroinflammatory disorders. Hackam et al. showed that the mitigating effects of Lacticaseibacillus rhamnosus HN001 are mediated by anti-inflammatory signalling via TLR9 (27). Inflammatory response under some pathological conditions such as necrotizing enterocolitis and allergies in children have also been shown to decrease due to immunomodulatory effects of probiotic strains.

Probiotic for Inflammatory and chronic inflammation of the gastrointestinal tract:

A. Inflammatory bowel disease (IBD):

More than 3.6 million people are estimated to be affected by Inflammatory bowel disease (IBD) across the globe (15, 16). IBD, including Crohn’s disease (CD) and ulcerative colitis (UC), are characterized by an abnormal activation of the immune system associated with the gut, resulting in a chronic inflammation of the digestive system. However, some other factors also seem to be involved in IBD such as genetic components (17,18), immunological disorders (19), environmental factors (20,21), pathogens (22, 23) and microbiota (24).

Both Th-1 and Th-2 activities have been observed in Crohn's disease (CD) and ulcerative colitis (UC), the two subtypes of IBD. Therefore, in IBD, there is often an overproduction of inflammatory cytokines leading to inflammation (7).

There have been many RCTs evaluating the effects of probiotics in IBD, associated with ample evidence suggesting that altered gut microbiota contribute to the initiation and progression of IBD. It has been well established that VSL #3, an eight-strain probiotic which includes Lactobacilli, Bifidobacilli, and Streptococcus thermophilus, is effective in ulcerative colitis, however, this and other probiotics were not effective in Crohn's disease (25). In a recent meta analysis of 27 trials, Ganji-Arejanaki et al. confirmed that VSL #3 was effective in UC and showed that probiotics S. boulardii, Lactobacilli (Lacticaseibacillus rhamnosus, Lactobacillus johnsonii), and VSL #3 were effective in patients with CD who also used corticosteroids (26).

The use of VSL #3 and Lactobacillus johnsonii after surgery for CD might be efficacious if the duration of treatment under study were longer. Ganji-Arejanaki et al. additionally concluded that in children aged 2–21 years with IBD (both CD and UC), Lactobacilli (Limosilactobacillus reuteri ATCC 55730, Lactobacillus rhamnosus strain GG, and VSL #3) confer a significant advantage (26).

Irritable bowel syndrome (IBS):

Irritable bowel syndrome is defined as recurrent abdominal pain at least one day weekly for more than 3 months, which is related to defecation and associated with a change in stool form (28). Most meta-analyses have shown efficacy of probiotics in treating IBS (29). Different probiotics have been studied, and the meta-analyses have shown considerable heterogeneity. Therefore, the role of probiotics in IBS is best described as “evolving but promising.”

Necrotizing enterocolitis (NEC):

It was reported that probiotics could prevent necrotizing enterocolitis ( NEC), a devastating disease of premature infants often resulting in bowel resection and short bowel syndrome. The first meta-analysis by Alfaleh and Bassler was published in 2008, showing benefit of probiotics in nine trials (30). Similarly, by 2017, more than 23 studies in 7325 infants showed that probiotics reduce the risk of developing NEC. This most recent meta-analysis by Thomas et al.showed that the risk of developing NEC was 3.9% if given probiotics and 6.6% if untreated with probiotics (relative risk of 0.57, 95% confidence interval (CI) 0.43–0.74, p < 0.0001) (31). One meta-analysis found that the benefit was restricted to multiple-strain probiotics and to Lactobacilli (32), while another meta-analysis (oppositely) found that the benefit pertained only to Bifidobacilli and multiple-strain probiotics (33). Dvorak’s group showed that Bifidobacterium bifidum stabilized the gut barrier via tight junction modification during experimental NEC (34).

Infant colic.

Babies who cry and fuss for more than 3 h daily have colic. The condition generally starts at 3 weeks of age, occurs on more than 3 days/week, and resolves after 3 months of age (hence the “rule of threes” (35). Microbial dysbiosis began to be linked to this condition and was confirmed by several groups and it was linked to gut inflammation (36). Therefore, colic might represent a condition for which probiotic treatment would be useful. Several meta-analyses have shown that the probiotic Limosilactobacillus reuteri, isolated from a Peruvian mother’s breast milk, reduces crying time and irritability in this condition (37, 38).

Respiratory infections.

It was reported that Lactobacillus and Bifidobacillus containing probiotics were found to improve outcomes in acute infectious diseases outside of the gastrointestinal tract, such as upper and lower respiratory tract illnesses in infants and college students (39,40). In one moderately large multicenter study in Italy, the addition of fermenting Lacticaseibacillus paracasei to milk or rice milk resulted in reduced episodes of gastroenteritis, rhinitis, otitis, laryngitis, and tracheitis (41). This finding suggested that the benefits to the host extend beyond local interactions in the intestinal tract between the gut organisms, enterocytes, and the immune system, perhaps involving microbial metabolites and/or migrating dendritic cells that reach distant locations such as the spleen and lymph nodes.

Nucleoside (adenosine) signalling.

Limosilactobacillus reuteri 17938 modifies the microbiota–adenosine-inosine receptor 2A (A2A) axis, which in turn inhibits TH1 and TH2 cell differentiation to reduce inflammation in the liver, lungs, gut, and skin (42,43). Remodelling gut microbiota with Limosilactobacillus reuteri 17938 markedly prolonged survival and reduced multiorgan inflammation in scurfy mice. One of the key mechanisms of Tregs is to control inflammatory effector T cells (Tems). In the absence of Tregs, the adenosine metabolite inosine at high doses may replace the effect of adenosine to interact with the A2A receptor and inhibit TH cell differentiation.


It is well established that Probiotics have impact on the immune system, both in vivo and in vitro and this interaction is directly linked to gut microbes, their polysaccharide antigens, and key metabolites produced by probiotic strains. The onset of inflammation may be associated with an imbalance in the intestinal microflora with relative predominance of ‘‘aggressive’’ bacteria and an insufficient concentration of protective or Probiotic species. Furthermore, this dysbiosis can be rectify by taking direct supplementation with probiotic bacteria. Overall, we can say that in inflammatory conditions or disease, probiotics appear to be safe and promising, but not proven as adjuvants to standard therapy.


1. Polman C.H., Reingold S.C., Banwell B., Clanet M., Cohen J.A., Filippi M., Fujihara K., Havrdova E., Hutchinson M., LJAon K. (2011): Diagnostic criteria for multiple Sclerosis: 2010 revisions to the McDonald criteria. Ann Neurol. Vol. 69, pp- 292–302.

2. Coyle PKJCLLiN (2016): Symptom management and lifestyle modifications in multiple Sclerosis. Continuum (Minneap Minn). Vol. 22, pp.815–36.\

3. Mielcarz D.W., Kasper L.H (2015): The gut microbiome in multiple sclerosis. Curr Treat Options Neurol. Vol.17(4), pp18.

4. Chiaravalloti N.D and DeLuca J. (2008): Cognitive impairment in multiple sclerosis. Lancet Neurol. Vol.7(12), pp1139-51.

5. C.E.West, M.L. Hammarström, and O. Hernell (2013): “Probiotics in primary prevention of allergic disease—follow-up at 8-9 years of age,” Allergy, Vol. 68 (8), pp.1015–1020.

6. Kashima S, Fujiya M, Konishi H (2015): Polyphosphate, an active molecule derived from probiotic Lactobacillus brevis, improves the fibrosis in murine colitis. Transl Res. Vol. 166(2),pp. 163- 175.

7. Davies J.M., Abreu M.T (2015). The innate immune system and inflammatory bowel disease. Scand J Gastroenterol. Vol. 50(1), pp. 24- 33.

8.Morelli L, Pellegrino P. A (2021): Critical evaluation of the factors affecting the survival and persistence of beneficial bacteria in healthy adults. Benef Microbes. Vol. 12(4), pp. 15- 25.

9. Ishizaki, A.; Bi, X.; Nguyen, L.V.; Matsuda, K.; Pham, H.V.; Phan, C.T.T.; Khu, D.T.K.; Ichimura, H (2017): Effects of Short-Term Probiotic Ingestion on Immune Profiles and Microbial Translocation among HIV-1-Infected Vietnamese Children. Int. J Mol. Sci. Vol. 18,pp.2185.

10.Esmaeili, S.A.; Mahmoudi, M.; Momtazi, A.A.; Sahebkar, A.; Doulabi, H.; Rastin, M. Tolerogenic probiotics (2017): Potential immunoregulators in Systemic Lupus Erythematosus. J. Cell. Physiol. Pp. 232.

11. Gasbarrini, G.; Bonvicini, F.; Gramenzi, A (2016): Probiotics History. J. Clin. Gastroenterol. Vol. 50, pp.116–119.

12. Yuying Liu , Jane J. Alookaran and J. Marc Rhoads (2018): Probiotics in Autoimmune and Inflammatory Disorders. Nutrients, Vol.10, pp. 1-19.

13. Xu F, Dahlhamer J.M., Zammitti E.P, Wheaton A.G, Croft J.B. (2018): Health-Risk Behaviors and Chronic Conditions Among Adults with Inflammatory Bowel Disease — United States. MMWR Morb Mortal Wkly Rep. Vol. 67, pp. 190–195.

14. Loftus E.V. (2004): Clinical epidemiology of inflammatory bowel disease: Incidence, prevalence, and environmental influences. Gastroenterology. Vol. 126, pp.1504-1517.

15. Molodecky N.A, Soon I.S, Rabi D.M, Ghali W.A, Ferris M., Chernoff G., Benchimol E.I, Panaccione R., Ghosh S., Barkema H.W, Kaplan G.G (2012): Increasing incidence and prevalence of the inflammatory bowel diseases with time, based on systematic review. Gastroenterology. Vol.142, pp.46-54.

16. Hampe J, Franke A, Rosenstiel P, Till A, Teuber M, Huse K, Albrecht M, Mayr G, De La Vega FM, Briggs J (2007): A genome-wide association scan of nonsynonymous SNPs identifies a susceptibility variant for Crohn disease in ATG16L1. Nat Genet. Vol. 39, pp. 207–211.

17. Hugot J.P, Chamaillard M, Zouali H, Lesage S, Cezard J.P, Belaiche J, Almer S, Tysk C, O’Morain CA, Gassull M (2001): .Association of NOD2 leucine-rich repeat variants with susceptibility to Crohn’s disease. Nature, Vol. 411, pp.599–603.

18. Bamias G, Nyce M.R, De La Rue S.A, Cominelli F (2005): New concepts in the pathophysiology of inflammatory bowel disease. Ann Intern Med. Vol.143, pp.895–904.

19. Shanahan F (2004):. Host-flora interactions in inflammatory bowel disease. Inflamm Bowel Dis. Vol. 10(Suppl 1), pp.16–24.

20.Danese S, Sans M, Fiocchi C (2004): Inflammatory bowel disease: the role of environmental factors. Autoimmun Rev. Vol. 3. Pp.394–400.

21. Chiodini R.J, Vankruiningen H.J, Thayer W.R, Merkal R.S, Coutu J.A (1984):Possible Role of Mycobacteria in Inflammatory Bowel-Disease.1. An Unclassified Mycobacterium Species Isolated from Patients with Crohns-Disease. Dig Dis Sci. Vol.29, pp.1073–1079.

22. Darfeuille-Michaud A, Boudeau J, Bulois P, Neut C, Glasser A.L, Barnich N, Bringer M.A, Swidsinski A, Beaugerie L, Colombel J.F (2004): High prevalence of adherent-invasive Escherichia coli associated with ileal mucosa in Crohn’s disease. Gastroenterology, Vol.127, pp.412–421.

23. Tannock G.W (2004): A special fondness for lactobacilli. Appl Environ Microbiol, Vol.70, pp.3189–3194.

24. Shen, J.; Zuo, Z.X.; Mao, A.P. (2014): Effect of probiotics on inducing remission and maintaining therapy in ulcerative colitis, Crohn’s disease, and pouchitis: Meta-analysis of randomized controlled trials. Inflamm. Bowel. Dis. Vol.20, pp.21–35.

25. Ganji-Arjenaki, M.; Rafieian-Kopaei, M. (2018): Probiotics are a good choice in remission of inflammatory bowel diseases: A meta-analysis and systematic review.J. Cell. Physiol. Vol. 233, pp.2091–2103.

26. Good, M.; Sodhi, C.P.; Ozolek, J.A.; Buck, R.H.; Goehring, K.C.; Thomas, D.L.; Vikram, A.; Bibby, K.; Morowitz, M.J.; Firek, B. (2014): Lactobacillus rhamnosus HN001 decreases the severity of necrotizing enterocolitis in neonatal mice and preterm piglets: Evidence in mice for a role of TLR9. Am. J. Physiol. Gastrointest. Liver Physiol. Vol.306, pp.1021–1032.

27. Simren, M.; Palsson, O.S.; Whitehead, W.E. (2017): Update on Rome IV Criteria for Colorectal Disorders: Implications for Clinical Practice. Curr. Gastroenterol. Rep. Vol. 19, pp.15–23.

28. Ford, A.C.; Quigley, E.M.; Lacy, B.E.; Lembo, A.J.; Saito, Y.A.; Schiller, L.R.; Soffer, E.E.; Spiegel, B.M.; Moayyedi, P. (2014): Efficacy of prebiotics, probiotics, and synbiotics in irritable bowel syndrome and chronic idiopathic constipation: Systematic review and meta-analysis. Am. J. Gastroenterol. Vol. 109, pp.1547–1561.

29. Alfaleh, K and Bassler, D (2008): Probiotics for prevention of necrotizing enterocolitis in preterm infants. Cochrane Database Syst. Rev. CD005496.

30. Thomas, J.P.; Raine, T.; Reddy, S.; Belteki, G (2017): Probiotics for the prevention of necrotising enterocolitis in very low-birth-weight infants: A meta-analysis and systematic review. Acta Paediatr. Vol.106, pp.1729–1741.

31. Chang, H.Y.; Chen, J.H.; Chang, J.H.; Lin, H.C.; Lin, C.Y.; Peng, C.C. (2017): Multiple strains probiotics appear to be the most effective probiotics in the prevention of necrotizing enterocolitis and mortality: An updated meta-analysis. PLoS ONE, 12, e0171579.

32. Aceti, A.; Gori, D.; Barone, G.; Callegari, M.L.; Di, M.A.; Fantini, M.P.; Indrio, F.; Maggio, L.; Meneghin, F.; Morelli, L. (2015): Probiotics for prevention of necrotizing enterocolitis in preterm infants: Systematic review and meta-analysis. Ital. J. Pediatr.Vo.41,pp.89–109.

33. Khailova, L.; Dvorak, K.; Arganbright, K.M.; Halpern, M.D.; Kinouchi, T.; Yajima, M.; Dvorak, B. (2009): Bifidobacterium bifidum improves intestinal integrity in a rat model of necrotizing enterocolitis. Am. J. Physiol. Gastrointest. Liver Physiol. Vol. 297, pp.940–949.

34. Wessel, M.A.; Cobb, J.C.; Jackson, E.B.; Harris, G.S., Jr.; Detwiler, A.C. (1954): Paroxysmal fussing in infancy, sometimes called colic. Pediatrics 1954, 14, 421–435.

35. Rhoads, J.M.; Collins, J.; Fatheree, N.Y.; Hashmi, S.S.; Taylor, C.M.; Luo, M.; Hoang, T.K.; Gleason, W.A.; Van Arsdall, M.R.; Navarro, F (2018): Infant Colic Represents Gut Inflammation and Dysbiosis. J. Pediatr.

36. Harb, T.; Matsuyama, M.; David, M.; Hill, R.J. Infant Colic-What works (2016): A Systematic Review of Interventions for Breast-fed Infants. J. Pediatr. Gastroenterol. Nutr. Vol. 62, pp. 668–686.

37. Sung, V.; D’Amico, F.; Cabana, M.D.; Chau, K.; Koren, G.; Savino, F.; Szajewska, H.; Deshpande, G.; Dupont, C.; Indrio, F. (2018): Lactobacillus reuteri to Treat Infant Colic: A Meta-analysis. Pediatrics Vol.141, e20171811.

38. Maldonado, J.; Canabate, F.; Sempere, L.; Vela, F.; Sanchez, A.R.; Narbona, E.; Lopez-Huertas, E.; Geerlings, A.; Valero, A.D.; Olivares, M. (2012): Human milk probiotic Lactobacillus fermentum CECT5716 reduces the incidence of gastrointestinal and upper respiratory tract infections in infants. J. Pediatr. Gastroenterol. Nutr. Vol.54, pp. 55–61.

39. Rautava, S.; Salminen, S.; Isolauri, E. (2009): Specific probiotics in reducing the risk of acute infections in infancy—A randomised, double-blind, placebo-controlled study. Br. J. Nutr. Vol. 101, pp.1722–1726.

40. Nocerino, R.; Paparo, L.; Terrin, G.; Pezzella, V.; Amoroso, A.; Cosenza, L.; Cecere, G.; De, M.G.; Micillo, M.; Albano, F. (2017):a Cow’s milk and rice fermented with Lactobacillus paracasei CBA L74 prevent infectious diseases in children: A randomized controlled trial. Clin. Nutr. Vol. 36, pp.118–125.

41. He, B.; Hoang, T.K.; Wang, T.; Ferris, M.; Taylor, C.M.; Tian, X.; Luo, M.; Tran, D.Q.; Zhou, J.; Tatevian, N. (2017): Resetting microbiota by Lactobacillus reuteriinhibits T reg deficiency-induced autoimmunity via adenosine A2A receptors. J. Exp. Med. Vol.214, pp. 107–123.

42. He, B.; Hoang, T.K.; Tran, D.Q.; Rhoads, J.M.; Liu, Y. (2017): Adenosine A2A Receptor Deletion Blocks the Beneficial Effects of Lactobacillus reuteri in Regulatory T-Deficient Scurfy Mice. Front. Immunol. Vol. 8, pp.1680.