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Gut microbiota and thyroid function

The gut microbiota plays a pivotal role in thyroid disorders, including Hashimoto thyroiditis, Graves’ disease and thyroid cancer. Recent data have suggested that microbes influence thyroid hormone levels through the regulation of iodine uptake, degradation, and enterohepatic cycling.

Studies have been shown that Lactobacillaceae and Bifidobacteriaceae are often reduced in hypothyroidism and hyperthyroidism. In Graves’ disease patients, the composition of the gut microbiota differs from that of healthy individuals, with a significant decrease in the relative abundance of Faecalibacterium prausnitzii, Butyricimonas faecalis, Bifidobacterium adolescentis and Akkermansia muciniphila compared to the control. Furthermore, a diagnostic model was developed using metagenome-assembled genomes of the gut microbiome, which may serve as a valuable predictor for Graves’ disease. The gut microbiota has the capacity to produce various neurotransmitters, such as dopamine, which can regulate the hypothalamus-pituitary axis and inhibit thyroid-stimulating hormone (TSH).

The Effects of Probiotics and prebiotics on thyroid function

 Numerous studies have been conducted to investigate the modulation of gut microbiota in order to restore dysbiosis in patients with thyroid disorders. Probiotics and prebiotics have demonstrated beneficial effects on thyroid diseases. Probiotics including bifidobacterium longum supplied with methimazole was implemented in nine patients with Graves’ disease for six months. The results showed a significant reduction in clinical thyroid indexes, including free T3, free T4, and thyrotropin receptor antibody (TRAb), while TSH levels increased compared to baseline. Another study explored the effects of a four-week treatment with a complex probiotics preparation consisting of Bifidobacterium infantis, Lactobacillus acidophilus, Enterococcus faecalis and Bacillus cereus in patients post-thyroid hormone withdrawal (THW) following thyroid cancer surgery. The treatment led to a decreased occurrence of complications such as dyslipidemia and constipation. However, the serum levels of free T4, free T3 and TSH showed no change between groups. Synbiotics, which are a mixture of probiotics and prebiotics, have also been examined. They have shown potential in reducing TSH and increasing freeT3 in patients with hypothyroidism. A strategy based on microbiome-directed therapies, involving supplementation with probiotics, prebiotics and synbiotics holds promise as a therapeutic approach for thyroid disorders.

Conclusion

There is a growing interest in investigating the potential role of probiotics or prebiotics supplementation to improve thyroid function in humans. A recent meta-analysis indicates that supplementation with probiotics/prebiotics has no significant effect on thyroid hormone levels, while showing a modest decrease in TRAb levels. However, the results have been inconsistent, and the probiotics or prebiotics are various in each randomized clinical trial, leading a mixed effect.

References

Provided by: Dr. Nazila Kassaian

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Gut-microbiota manipulation

gut microbiome

Nowadays, some strategies like probiotics, prebiotics, post biotics, synbiotics or fecal microbiota transplantation (FMT) rely on adding individual, several, or a whole consortium of living microbial organisms to exclude disease-causing microbes and provide health-promoting benefits. Moreover, bacteriocins and bacteriophages present another potential strategies to remove specific pathogens associated with the onset of a particular diseases; however, their exploration as therapeutics in humans is still in its infancy.

Gut-microbiota targeted therapeutics in IBD

The therapeutic potential of these agents in inflammatory bowel disease (IBD) comprising ulcerative colitis (UC) and Crohn’s disease (CD), has been evaluated in a meta-analysis of 32 randomized controlled trials (RCTs). The authors found that these therapeutics considerably increased the number of beneficial intestinal bacteria (particularly Bifidobacterium), induced or maintained IBD remission and lowered UC disease activity index whilst not affecting IBD recurrence. Subgroup analyses showed that combining probiotics and prebiotics with conventional therapies was more effective in reducing these parameters than traditional treatments alone, while synbiotic treatment seemed to be more effective than prebiotics and probiotics alone. Additionally, the study suggested that probiotics containing Bifidobacterium, Lactobacillus, or more than one bacterial strain were more effective as IBD therapeutics and proposed doses from 10۱۰ to 10۱۲ colony forming units (CFU)/day as reference dose. The severity of inflammation and disease activity has also been proposed to influence the effectiveness of microbiota-targeted therapeutics in IBD.

Moreover, the data could suggest that the microbiota-modulatory efficacy of prebiotics decreases going from healthy, at-risk subjects to those with inactive and active IBD, indicating their potential in IBD primary prevention and treatment in a less inflamed gut.

Gut-microbiota targeted therapeutics in diarrhea

The effect of probiotics on chronic diarrhea, associated with different intestinal disorders like irritable bowel syndrome (IBS) and functional diarrhea, was evaluated. Yang et al have shown that intake of Lactiplantibacillus plantarum CCFM1143 for 4 weeks can be effective in managing chronic diarrhea symptoms in patients compared to placebo (maltodextrin). Moreover, it has been demonstrated that prebiotic consumption decreases the abundance of Bacteroides and Eggerthella, increases the abundance of beneficial species like Akkermansia, Terrisporobacter, and Anaerostipes, and stimulates acetic and propionic acid production. These data suggesting the potency of this probiotic strain and prebiotic can improve the microbiota imbalance and clinical symptoms in functional bowel disorders.

Gut-microbiota targeted therapeutics in Helicobacter pylori infection

The therapeutic potential of probiotics alone or in combination with standard treatments has also been evaluated in Helicobacter pylori infection. One study showed that consumption of a probiotic drink containing fermented milk with Lacticaseibacillus paracasei CNCM I-1518 and I-3689, L. rhamnosus CNCM I-3690, and four yogurt strains for 28 days induced faster gut microbiota recovery after H. pylori eradication, reducing the abundance of potentially pathogenic bacteria (e.g., Escherichia-Shigella and Klebsiella) and increasing fecal SCFA generation compared to the control drink. Another study evaluated the therapeutic effects of a probiotic including Bifidobacterium infantis, Lactobacillus acidophilus, Enterococcus faecalis, and Bacillus cereus, provided alone or in combination with quadruple eradication therapy (PPI, bismuth, and two antibiotics) for 2 weeks, on gastric microbiota recovery in H. pylori-infected individuals. Results showed that 2 months after treatment, the quadruple therapy did not restore gastric microbiota of H. pylori-positive subjects to an uninfected state; however, adjuvant probiotic therapy contributed to its recovery by improving microbial diversity, reducing the abundance of potentially harmful bacteria (e.g., Fusobacterium, Campylobacter and Proteobacteria) and increasing the beneficial bacteria (e.g., Lachnospiraceae, Ruminococcaceae, Eubacterium ventriosum). By contrast, probiotic monotherapy was ineffective in H. pylori abolition and failed to restore gastric microbiota, with observed alterations in microbiota structure, increased putative pathogenic bacteria, and no induction of beneficial bacteria.

written by: Dr.Nazila Kassaian

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The effects of Biotics in Gut Barrier Integrity

Introduction

Chronic inflammation which is observed in inflammatory bowel diseases (IBD), Overweight/ obesity, cardiovascular and neurodegenerative diseases, type I diabetes (T1D), depression /anxiety have recently become a real challenge. One of the factors potentially linking these diseases is the increased permeability of the intestinal barrier. The intestinal barrier consists of the mucus layer, intestinal microbiota, intestinal epithelial cells (IECs) and lamina propria. The intestinal barrier is characterized by selective permeability, which means that ions, water, and low-molecular substances can freely pass through it, while it is impermeable to toxins, pathogens, macromolecules, and food allergens. When these substances leave the intestine, the immune system is over-activated, resulting in the induction of inflammation, which, if it persists for a long time, leads to serious health consequences. Therefore, maintaining the integrity of the intestinal barrier is one of the most important aspects of ensuring health. The paracellular space between enterocytes is sealed by tight junctions (TJs), adherence junctions (AJs) and desmosomes. The role of the microbiota in preserving the intestinal barrier largely depends on the fact that commensal microbes adhere to the intestinal mucosa and constitute an additional protective layer. Modulation of microbiota composition by biotics appears to be an interesting concept to enhance the gut barrier, to treat or even prevent the onset or aggravation of chronic diseases.

Summary and Future Perspectives

Increasing intestinal permeability causes chronic inflammation, which is one of the etiological factors of inflammatory diseases, which presently constitute a global challenge. The so-called “leaky gut” is associated with diseases such as IBS, CD, celiac disease, chronic liver disease, diabetes, food allergies and sensitivities, polycystic ovary syndrome, depression and anxiety. The knowledge of the activity of various biotics is becoming extented. An increasing number of scientific reports indicate that the microbiota and general homeostasis in the intestinal environment are factors that guarantee health.
The modern lifestyle and model of nutrition lead rather to dysbiosis, which is one of the reasons for intestinal permeability. The multiplicity and diversity of diseases associated with the increase in intestinal permeability indicate the need for strategies to restore gut balance and explain the mechanisms underlying the maintenance of the intestinal barrier function. In this context, the use of biotics seems to be promising. In both in vitro and in vivo experimental models, probiotics, prebiotics, synbiotics and postbiotics were shown to enhance the intestinal barrier. Most studies indicate the regulation of gene expression of TJ proteins as a potential mechanism of biotics action on the gut barrier. The positive effect of biotics was repeatedly reported by in vitro and in vivo models. However, it was rarely confirmed in human trials. Another problem underlined in this review is that many clinical trials were conducted with the subjects without ongoing leaky gut; thus, improvement cannot be expected. Therefore, there is a need for well-designed clinical trials clearly demonstrating the role of biotics in restoring the integrity of the intestinal barrier. The available clinical trials on biotics have little focus on gut barrier function but rather on systemic effects.
Therefore, further clinical trials are needed to show the relationship between biotics and gut barrier function in human subjects. Moreover, there is a need to explore whether alternative biotics, such as postbiotics, can affect the gut barrier. It is also necessary to understand the mechanisms that are regulated by various biotics for restoring intestinal integrity, which will allow for the development of therapies eliminating the causes of diseases associated with the leaky gut rather than just symptomatic treatment.

prepared by: Nazila Kassaian

 References

Kocot AM, Jarocka-Cyrta E, Drabińska N. Overview of the Importance of Biotics in Gut Barrier Integrity. International Journal of Molecular Sciences. 2022 Mar 7; 23(5):2896.

Paone, P.; Cani, P.D. Mucus Barrier, Mucins and Gut Microbiota: The Expected Slimy Partners? Gut 2020, 69, 2232–۲۲۴۳.