Credit: “Create an image themed ‘gut-brain axis’; try to be scientific and include microbiota” prompt. ChatGPT, 25 Oct. version, OpenAI, 25 Oct. 2024, https://chatgpt.com/c/671c0974-4dd0-8007-9f98-695c559e55f2
Author: Helen Wu
Editor: Altay Shaw
All animals, including humans, have evolved closely alongside microbial communities made up of bacteria, fungi, viruses, and archaea. These microorganisms, collectively known as microbiota, inhabit every body surface exposed to the environment. In humans, the gastrointestinal tract hosts the largest population of microbiota, with their influence extending far beyond digestion. The bacterial microbiome in humans is vast, with a population comparable in number to human cells and approximately 232 million genes that provide a metabolic capacity comparable to that of the human liver.
Some of the most important metabolic byproducts from the gut microbiome are short-chain fatty acids (SCFAs) and cell wall components. They keep the gut in balance and make sure the enteric nervous system works properly. For instance, studies have shown that introducing SCFA-producing gut microbiota in mouse models suppresses certain gut-to-brain connections. Furthermore, bacterial-derived SCFAs, in conjunction with cytokines and chemokines, can modify microglia-mediated immune responses, closely associated with stress, neurodegeneration, and neuropsychiatric disorders. Mice lacking appropriate gut microbiota populations also exhibit increased permeability of the blood-brain barrier, a hallmark of many neurological, infectious, or autoimmune diseases.
Recent research has highlighted distinct microbiome profiles in individuals with depression, altered stress resilience, and other psychiatric disorders. A pilot human study demonstrated that administering Bifidobacterium longum NCC3001 significantly alleviated depression in individuals with irritable bowel syndrome. Similarly, Lactobacillus has been shown to improve symptoms of stress-induced behavioural despair. These findings underscore the previously underestimated importance of the microbiome.
However, many questions remain unanswered. For example, the extent to which the microbiome influences neuronal and hormonal pathways via the gut-brain axis is still unclear. Furthermore, there is a dearth of evidence regarding the potential impact of the microbiome on the peripheral nervous system, particularly in terms of its ability to influence signalling between the central and peripheral nervous systems. Neuropsychiatric and neurodegenerative disorders involve complex biological networks encompassing chemical, neuronal, and immunological aspects, and decoding these intricate signalling pathways will require further efforts from cell biologists. Future research should also explore sex differences in microbiome functions, and more human clinical trials are needed.
Given the microbiome’s significance, probiotic supplements have gained popularity, with many people consuming them regularly for their perceived health benefits. In 2013, the International Scientific Association for Probiotics and Prebiotics (ISAPP) redefined probiotics as “live microorganisms that, when administered in adequate amounts, confer a health benefit on the host.” Certain probiotics have been shown to maintain the epithelial barrier, competitively exclude pathogenic organisms, and prevent conditions like urogenital infections, diarrhoeal diseases, inflammatory bowel diseases, diabetes, obesity, and even cancer. These supplements often contain billions of probiotic bacteria per serving, making them the most concentrated source of probiotics among functional foods. However, despite the frequent emphasis on the benefits, one should not overlook the potential risks.
Recent studies have raised concerns about the long-term safety of probiotic supplements. For vulnerable groups, such as individuals with diabetes, cancer, or other forms of immunosuppression, probiotics may lead to regional or systemic infections due to overgrowth or bloodstream penetration. Some side effects, such as autoimmune diseases triggered by certain microbial metabolites, can be severe. Additionally, these supplements may carry antibiotic-resistant genes that could transfer to gut bacteria, posing a significant health risk. Moreover, research has shown that probiotics in supplements often struggle to survive the harsh conditions of the human gut, such as exposure to acids and bile salts. Despite their resistance to multiple antibiotics, probiotics may not be as effective as commonly believed. Therefore, regulatory bodies should conduct rigorous safety analyses of all food supplements before they are made available to the public. More human clinical trials are needed, and potential side effects and target consumers should be clearly labelled on these products.
In addition to probiotics, prebiotics serve as an alternative or complement. In 2007, the FAO (Food and Agriculture Organization of the United Nations) and WHO (World Health Organization) defined prebiotics as “a nonviable food component that confers a health benefit on the host associated with modulation of the microbiota.” Synbiotics, which combine both probiotic and prebiotic properties, can offer superior benefits by addressing challenges in the survival of probiotics within the gastrointestinal tract. Recent research has also introduced the concept of “designer probiotics,” which are genetically engineered to possess specific functionalities or features beyond those of the original microbiome strains. According to a 2017 review, some designer probiotics have entered clinical trials for treating inflammatory bowel disease.
Natural synbiotics, particularly those found in fermented foods, have been proposed by researchers to be included in dietary guidelines due to their potential health benefits. These foods not only offer direct nutritional value from the fermentation process but also provide a source of beneficial synbiotics that may survive gastric transit. Common healthy fermented foods, such as beans, grains, dairy products, and vegetables, have been recommended by many nutrition experts.
In conclusion, our understanding of the human microbiome has grown considerably, highlighting its influence on various aspects of health, from digestion to mental well-being. While probiotics and prebiotics show potential benefits, it is important to approach their use with careful consideration, keeping in mind both the possible advantages and risks. As research progresses, the role of microbiota in health and disease prevention continues to be a promising area of study. Stay tuned as science continues to explore this fascinating frontier!
Reference list
Das, T.K. et al. (2022) ‘Current status of probiotic and related health benefits’, Applied Food Research, 2(2), p. 100185. Available at: https://doi.org/10.1016/J.AFRES.2022.100185.
Hill, C. et al. (2014) ‘The International Scientific Association for Probiotics and Prebiotics consensus statement on the scope and appropriate use of the term probiotic’, Nature Reviews Gastroenterology & Hepatology 2014 11:8, 11(8), pp. 506–514. Available at: https://doi.org/10.1038/nrgastro.2014.66.
Leeuwendaal, N.K. et al. (2022) ‘Fermented Foods, Health and the Gut Microbiome’, Nutrients, 14(7). Available at: https://doi.org/10.3390/NU14071527.
Liu, L., Huh, J.R. and Shah, K. (2022) ‘Microbiota and the gut-brain-axis: Implications for new therapeutic design in the CNS’, eBioMedicine, 77, p. 103908. Available at: https://doi.org/10.1016/J.EBIOM.2022.103908/ASSET/A7DAE745-DFD5-4CC1-95E0-4BF7A636F34F/MAIN.ASSETS/GR3.JPG.
Marin, I.A. et al. (2017) ‘Microbiota alteration is associated with the development of stress-induced despair behavior’, Scientific reports, 7. Available at: https://doi.org/10.1038/SREP43859.
Markowiak, P. and Ślizewska, K. (2017) ‘Effects of Probiotics, Prebiotics, and Synbiotics on Human Health’, Nutrients, 9(9). Available at: https://doi.org/10.3390/NU9091021.
Morais, L.H., Schreiber, H.L. and Mazmanian, S.K. (2020) ‘The gut microbiota–brain axis in behaviour and brain disorders’, Nature Reviews Microbiology 2020 19:4, 19(4), pp. 241–255. Available at: https://doi.org/10.1038/s41579-020-00460-0.
Muller, P.A. et al. (2020) ‘Microbiota modulate sympathetic neurons via a gut-brain circuit’, Nature, 583(7816), pp. 441–446. Available at: https://doi.org/10.1038/S41586-020-2474-7.
Patra, F. et al. (no date) ‘Engineered probiotics and pharmabiotics: Application in therapeutics and prophylaxis’, epubs.icar.org.inF Patra, R Duary, S Ganguly, A DasIndian J. Dairy Sci, 2017•epubs.icar.org.in, 70(2), p. 2017. Available at: https://epubs.icar.org.in/index.php/IJDS/article/download/49168/pdf/174863 (Accessed: 1 September 2024).
Wang, Yuxuan et al. (2020) ‘Probiotic Supplements: Hope or Hype?’, Frontiers in Microbiology, 11. Available at: https://doi.org/10.3389/FMICB.2020.00160/FULL.
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