Monday article #50: The association of our gut microbiota and immune-related diseases

Figure 1. An illustration of gut microbes [1]

Our gut microbiota consists of the whole intestinal microbial collection, including trillions of microorganisms and at least 1000 different bacterial species [2]. Commensals are microorganisms that lives in harmony with humans, and this includes many of the microbes in our gut microbiota. The composition of the gut microbiota varies between each individual, depending on the host gender, age, genetics, treatments, diet, and many other factors. The gut microbial community is beneficial to us in many ways, including, but not limited to, detoxification, digestion, nutrient production, protection from pathogens, and regulation of the immune system, through various mechanisms.

Through the production of small molecules that mediate host-microbial interaction, these commensal microorganisms modulate the immune responses and affect the activation threshold for stimulations of the immune response towards pathogens [3]. An example of the molecule produced is short-chain fatty acids (SCFAs), which are released by microbes, such as Bifidobacteria, when they ferment indigestible carbohydrates from our diet. SCFAs function as a source of energy for the cells in our gut and stimulate the expansion of regulatory T cells. They also exhibit anti-inflammatory properties on our immune cells by regulating the expression of pro-inflammatory cytokines such as tumour necrosis factor-α (TNF-α). In addition, SCFAs play a role in the maintenance of intestinal barrier integrity to protect us from food antigens and other harmful substances in the gut lumen [4]. The production of SCFAs also reduces gut pH, hence preventing the colonization of pathogenic E. coli bacteria.

Besides from the production of molecules such as SCFAs, the microbes in our gut can also reduce pathogenic bacteria’s virulence factors, which are substances that allow the bad bacteria to cause disease. For example, the pathogenic bacteria Shigella flexneri needs oxygen for the release of their virulence factors. However, commensal bacteria such as Enterobacteriaceae uses up oxygen in the gut, hence preventing secretion of virulence factors by Shigella [5].

Under normal conditions, a balance is maintained between the commensals and pathogens. However, if an imbalance were to occur, it will lead to the development of a pathological state known as “gut dysbiosis” [6]. Since the gut microbiota is crucial for shaping and modulating immune responses, gut dysbiosis has been linked to several autoimmune and immune-mediated diseases, such as Type 1 diabetes and inflammatory bowel disease.

Type 1 diabetes (T1D)

Figure 2. Common symptoms of Type 1 Diabetes [7]

Several evidence have indicated that dysbiosis of the microbiota play a crucial role in the development (pathogenesis) of Type 1 diabetes (T1D), which is a disease where antibodies produced against the body’s own tissues (autoantibodies) attacks insulin-producing cells in the pancreas. A study conducted by Knip and Honkanen [8] showed that individuals with positive autoantibodies against pancreatic cells had a higher Bacteroidetes/Firmicutes ratio in the gut microbiota. Besides that, Bacteroides dorei amounts were found to be significantly high in individuals with high risk of T1D and were associated with positive autoantibodies [9] while SCFAs-producing bacteria were reduced in T1D [10]. In addition, the development of diabetes is affected by a high-fat and high-sugar diet, which causes dysbiosis of our gut microbiota, particularly a decrease in Bifidobacteria species [11]. As mentioned previously, the Bifidobacteriaspecies can produce SCFAs, which play a role in the regulation of the immune system. These SCFAs have been found to limit the frequency of autoimmune cells and protect against T1D [12].

Inflammatory bowel disease (IBD)

Figure 3. Inflammatory bowel disease [13]

Dysregulation of the gut microbiota is also involved in the pathogenesis of inflammatory bowel disease (IBD), an autoimmune disease that affects the gastrointestinal tract. For example, it has been demonstrated that patients with IBD have beneficial effects from antibiotic treatment. Besides that, the gut microbiota composition of IBD patients as compared to individuals without the disease differ greatly. In IBD patients, a decrease in Firmicutes and Bacteroides species and an increase in proteobacteria was found [14]. It was also found that certain microbial species, such as K. pneumoniae and P. mirabilis, work together with other members of the microbial community to induce inflammation and subsequently IBD [15]. On the other hand, there are also beneficial commensal bacteria, such as B. fragilis, that can ameliorate the disease by stimulating production of anti-inflammatory cytokines and decreasing release of pro-inflammatory cytokines by immune cells [16]. These findings suggest that the gut microbiota composition is vital for the development of IBD.

Conclusion

Although we do not see the trillions of microorganisms inhabiting our gut, they are extremely important for our health. Dysbiosis of the gut microbiota is involved in the development of various diseases, including, but not limited to, inflammatory bowel disease and type 1 diabetes. Therefore, a balanced diet of gut-healthy foods such as vegetables, legumes, fruits, and yoghurt, along with controlled consumption of high-fat and high-sugar foods can promote gut health and aid in the prevention of various microbiota-associated diseases.

References

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[7] Buoy. (n.d.) What is type 1 diabetes? Retrieved from: https://www.buoyhealth.com/learn/type-1-diabetes

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This article was prepared by Phoebe Tee