The Interaction Between Gut Microbiota and Intestinal Immunity in Irritable Bowel Syndrome (IBS)

July 28, 2024 8 min read

Exploring the crosstalk in irritable bowel syndrome between the gut microbiota and intestinal immunity - Cover Image

It’s estimated that around 11% of the world’s population is affected by IBS[i], a debilitating and often misunderstood issue.

However, what is clear from numerous amounts of research is that there is a crosstalk between the gut microbial community and the intestinal immune system that can promote the development of IBS. In this article, we’ll explore the mechanisms behind the progression of the condition.

What is IBS?

Before we progress, it might be helpful if we do a quick overview of what irritable bowel syndrome is and what it can mean for sufferers.

IBS is a common chronic gastrointestinal complaint that’s estimated to affect up to 16% of the US population alone, at a yearly cost of more than $1 billion[ii]. There is no specific diagnostic test available for IBS because it is a myriad of gastric symptoms, occurring due to a diverse dysfunction of the gut-brain axis.

IBS is a lifelong condition and although there is no cure, some simple lifestyle changes and medications are available to help effectively manage the symptoms.

Symptoms and types of IBS

The most common IBS symptoms include abdominal pain and abnormal bowel movements. However, there are different types of IBS based on the patterns of your bowel movements. The different types are:

  • IBS with constipation (IBS-C):Common symptoms are bloating, abdominal pain, and hard, infrequent stools
  • IBS with diarrhea (IBS-D):Similar symptoms to IBS-C but with loose stools and a sudden urge to go to the toilet
  • IBS with mixed bowel habits (IBS-M):A type of IBS where the individual experiences both constipation and diarrhea episodes

Pathophysiology of IBS

The pathophysiology of IBS remains relatively unclear. For example, it has long been considered to have no structural or biochemical explanation, which can make treatment difficult. However, some doctors believe this idea is outdated[iii].

Emerging research suggests that there are possible mechanisms for dysfunction in the gut-brain axis that could contribute to the development of IBS. Other factors include:

  • Genetics
  • Chronic infections
  • Diet
  • Psychological

More nuanced research is revealing that the gut microbiome and the gut mucosal immune system play important roles in the development of irritable bowel syndrome. Hanning et al., (2021) found that gut barrier dysfunction was present in a significant number of IBS patients. Their meta-analysis revealed that 37-62% of IBS-D and 4 to 25% of IBS-C patients presented with increased gut permeability. Therefore, the analysis suggests that a dysregulated intestinal barrier could be associated with some of the IBS symptoms, including abdominal pain, changes in bowel movements, and the onset of the condition[iv].

Further studies have discovered that the gut microbiota of IBS patients is significantly altered with a reduction in microbial richness[v]. Other studies have identified that the broad-spectrum antibiotic, rifaximin, improves bloating and discomfort in some people with IBS, while animal studies show it downregulates proinflammatory factors and improves a leaky gut[vi].

What does all this mean?

In short, it means the gut immune system and microbiota could have a large stake in the development and progression of IBS. So, using a review by Chen et al., (2023) as a basis, we’ll delve into the role of each of these components in the pathogenesis of IBS.

Gut microbiota in IBS

The human gut is the residence of a myriad of bacteria, viruses, archaea, and fungi that make up a diverse microbial community. It has a wealth of functions for its human host and is involved in maintaining gut homeostasis, nutrient absorption, protection against invaders, and immunity. However, the key to a properly functioning microbiome is balance, if it falls out of kilter, then there’s a high risk of inflammation and the development of disease[vii]

Studies, such as one by Sciavilla et al., (2021), have found that the gut microbiota of IBS patients looks different to a healthy individual. For example, they found that the microbiota of IBS patients was depleted of health-promoting bacteria, like  Faecalibacterium  and  Roseburia,  but enriched with pro-inflammatory species, such as:

  • Enterobacteriaceae
  • Streptococcus
  • Fusobacteria
  • Gemella
  • Rothia[viii]

Zhuang et al., (2018) noted that in IBS-D-affected individuals there was an increase in  Bacteroidetes  and a decrease in  Firmicutes,  suggesting that alterations in the composition of the microbiota could be associated with the development of IBS[ix].

Intestinal Mucosal Immunity in IBS

The intestinal mucosal immune system functions separately from the systemic system charged with protecting the body. In the gut, the mucosal immune system is responsible for protecting against invading pathogens whilst remaining neutral in the presence of commensal microbes and food. To complete its mission, the system is comprised of unique cells and functions[x].

What does the intestinal mucosal immunity consist of?

  • Intestinal mucous layer:A layer of epithelial cells made up of water, electrolytes, and mucin which acts as a barrier to protect the epithelium, guard against pathogens, and nourish friendly bacteria, like  Akkermansia.
  • Intestinal epithelial cells (IECs):These include Paneth cells, goblet cells, enteroendocrine cells and absorptive enterocytes can secrete special defence factors to prevent the invasion of pathogens and to mediate the immune response to maintain homeostasis in the gut. IECs also communicate with intestinal intraepithelial lymphocytes, and immune cells, to suppress inflammation, promote repair along the epithelial lining, and maintain gut barrier integrity.
  • Gut-associated lymphoid tissue (GALT):These cells include Peyer’s patches and are situated through the gastrointestinal tract to protect the host against infection from invading pathogens[xi].
  • Enteric nervous system (ENS):The largest and most complex of the peripheral immune system, the ENS regulates the immune response and neurotransmitter and cytokine levels with the capability of increasing the defence of the gut barrier.

Overall, intestinal mucosal immunity is essential for maintaining gut homeostasis by distinguishing between good and bad triggers, such as pathogenic bacteria (bad) and probiotic bacteria (good).

However, if this system becomes compromised, the balance and harmony within the gut is disturbed, which increases the likelihood of disease, including irritable bowel syndrome.

Talley et al., (2021) found that intestinal epithelial cells increased in the ileum and cecum in IBS-D patients. While other studies have found that the expression of occludins (tight junction proteins) is reduced in people with IBS. Tight junction proteins are like the gatekeepers between the gut and the rest of the body[xii].

Research by Bertiaux-Vandaële et al., (2011) demonstrated that a reduced expression of occludin was present in people who experienced intense abdominal pain as part of their IBS symptoms. They also conclude that changes in tight junction proteins in the gut barrier could promote the development of IBS[xiii].

Interrupted crosstalk between the gut microbiota and intestinal immunity affects gut homeostasis

It’s the dynamic interplay between these two components, the gut microbiota and the intestinal immune system, which is central to keeping the balance and promoting good health.

This crosstalk is especially important for IBS because disruptions in either one of these can manifest into chronic and debilitating symptoms. How this occurs is multifaceted and involves a combination of cellular, molecular, and biochemical pathways.

Over the past few decades, evidence has come to light showing that there needs to be balance for the human body to fend off and manage invaders. This balance is so important as it is only with balanced gut microbiota, that we can produce massively important biochemical products such as short-chain fatty acids, (SCFAs)[xiv].

SCFAs have been seen to be in low numbers in many chronic illnesses, but especially IBS, as seen in a study by Jiang, et al (2022). It is not low numbers of SCFAs that are in question, but more their composition. Ultimately, this could suggest that an overpopulation of bad bacteria and an underpopulation of health-promoting species results in disproportionate levels of SCFAs in the wrong locations, leading to interruption of the crosstalk, and the subsequent manifestation of debilitating symptoms[xv].  

The protective role of HMOs in IBS

One potential and promising avenue for SCFA production and alleviation of IBS symptoms is human milk oligosaccharides (HMOs).

Over the past decade, research using both human and mouse subjects has looked at the interaction between gut inhabitants and HMOs. The studies have used a 5 g or 10 g dose per day of the HMOs 2’-Fucosyllactose (2’-FL) and lacto-N-neotetraose (LNnT), at a mix ratio of 4:1 respectively.

In 2020, Palsson et al. conducted a multicentre open-labelled study on 317 IBS patients. Of those, 245 completed the trial where bowel movements, stool consistency, symptom severity, and quality of life were assessed from baseline to 12 weeks. Symptom improvements were mostly seen in the 4th week of intervention, with the side effects being mild gastrointestinal flatulence, pain and discomfort. However, the results concluded that supplementation of HMOs improves the symptoms and quality of life for IBS sufferers without any substantial side effects[xvi].  

Are you looking to restore your gut health and interested in how HMOs can support this? Our PureHMO® IBS Support with IBS Defend probiotic delivers a unique blend of 2’-FL and LNnT, which are clinically proven to relieve the symptoms of IBS, alongside  Lactobacillus acidophilus,  specifically developed for IBS relief.

Summary

IBS is a common yet debilitating gut issue that presents with a myriad of symptoms, and has no cure. Research shows that the gut microbiota composition and intestinal mucosal immunity have significant roles in its development.

If you are keen to get your gut microbiome back in balance or looking for prebiotic and probiotic products to help support your gut health, browse our store.

Written byLeanne Edermaniger, M.Sc. Leanne is a professional science writer who specializes in human health and enjoys writing about all things related to the gut microbiome.    

Sources

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[ii] Camilleri M. Diagnosis and treatment of irritable bowel syndrome. JAMA. 2021 Mar 2;325(9):865. doi:10.1001/jama.2020.22532

[iii] Holtmann GJ, Ford AC, Talley NJ. Pathophysiology of irritable bowel syndrome. The Lancet Gastroenterology & Hepatology. 2016 Oct;1(2):133–46. doi:10.1016/s2468-1253(16)30023-1

[iv] Hanning N, Edwinson AL, Ceuleers H, Peters SA, De Man JG, Hassett LC, De Winter BY, Grover M. Intestinal barrier dysfunction in irritable bowel syndrome: a systematic review. Therap Adv Gastroenterol. 2021 Feb 24;14:1756284821993586. doi: 10.1177/1756284821993586. PMID: 33717210; PMCID: PMC7925957.

[v] Tap J, Derrien M, Törnblom H, Brazeilles R, Cools-Portier S, Doré J, et al. Identification of an intestinal microbiota signature associated with severity of irritable bowel syndrome. Gastroenterology. 2017 Jan;152(1). doi:10.1053/j.gastro.2016.09.049

[vi] Burns GL, Talley NJ, Keely S. Immune responses in the irritable bowel syndromes: time to consider the small intestine. BMC Med. 2022 Mar 31;20(1):115. doi: 10.1186/s12916-022-02301-8. PMID: 35354471; PMCID: PMC8969236.

[vii] Thursby E, Juge N. Introduction to the human gut microbiota. Biochem J. 2017 May 16;474(11):1823-1836. doi: 10.1042/BCJ20160510. PMID: 28512250; PMCID: PMC5433529.

[viii] Sciavilla P, Strati F, Di Paola M, Modesto M, Vitali F, Cavalieri D, Prati GM, Di Vito M, Aragona G, De Filippo C, Mattarelli P. Gut microbiota profiles and characterization of cultivable fungal isolates in IBS patients. Appl Microbiol Biotechnol. 2021 Apr;105(8):3277-3288. doi: 10.1007/s00253-021-11264-4. Epub 2021 Apr 10. PMID: 33839797; PMCID: PMC8053167.

[ix] Zhuang X, Tian Z, Li L, Zeng Z, Chen M, Xiong L. Fecal Microbiota Alterations Associated With Diarrhea-Predominant Irritable Bowel Syndrome. Front Microbiol. 2018 Jul 25;9:1600. doi: 10.3389/fmicb.2018.01600. PMID: 30090090; PMCID: PMC6068233.

[x] WERSHIL B, FURUTA G. 4. gastrointestinal mucosal immunity. Journal of Allergy and Clinical Immunology. 2008 Feb;121(2). doi:10.1016/j.jaci.2007.10.023

[xi] Donaldson DS, Else KJ, Mabbott NA. The Gut-Associated Lymphoid Tissues in the Small Intestine, Not the Large Intestine, Play a Major Role in Oral Prion Disease Pathogenesis. J Virol. 2015 Sep;89(18):9532-47. doi: 10.1128/JVI.01544-15. Epub 2015 Jul 8. PMID: 26157121; PMCID: PMC4542385.

[xii] Suzuki T. Regulation of the intestinal barrier by nutrients: The role of tight junctions. Anim Sci J. 2020 Jan-Dec;91(1):e13357. doi: 10.1111/asj.13357. PMID: 32219956; PMCID: PMC7187240.

[xiii] Bertiaux-Vandaële N, Youmba SB, Belmonte L, Lecleire S, Antonietti M, Gourcerol G, Leroi AM, Déchelotte P, Ménard JF, Ducrotté P, Coëffier M. The expression and the cellular distribution of the tight junction proteins are altered in irritable bowel syndrome patients with differences according to the disease subtype. Am J Gastroenterol. 2011 Dec;106(12):2165-73. doi: 10.1038/ajg.2011.257. Epub 2011 Oct 18. PMID: 22008894.

[xiv] den Besten G, van Eunen K, Groen AK, Venema K, Reijngoud DJ, Bakker BM. The role of short-chain fatty acids in the interplay between diet, gut microbiota, and host energy metabolism. J Lipid Res. 2013 Sep;54(9):2325-40. doi: 10.1194/jlr.R036012. Epub 2013 Jul 2. PMID: 23821742; PMCID: PMC3735932.

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[xvi] Palsson OS, Peery A, Seitzberg D, Amundsen ID, McConnell B, Simrén M. Human Milk Oligosaccharides Support Normal Bowel Function and Improve Symptoms of Irritable Bowel Syndrome: A Multicenter, Open-Label Trial. Clin Transl Gastroenterol. 2020 Dec;11(12):e00276. doi: 10.14309/ctg.0000000000000276. PMID: 33512807; PMCID: PMC7721220.


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