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Gut bugs, probiotics, and fibrosis

Updated: Aug 10, 2023

You and I have a lot in common – we both have around 100 trillion gut bugs [1], which are a diverse array of bacteria, fungi, viruses and archaea that are referred to as the microbiota [2]. Your gut reaction to this might be “eeew!”, but these bugs (microbes) play a huge role in good health. Indeed, most of them are beneficial, and you need your good gut microbes to survive [2]. Microbes produce essential amino acids, vitamins and short-chain fatty acids that enter the blood stream and are essential for many body functions, including immune function [1, 2], neurobiology and metabolism [2]. Other roles the gut microbiota play include digesting food, modifying drugs and eliminating toxins [2].


Of course there can be a downside too. An imbalance in gut microbiota has been implicated in lung fibrosis [3], liver fibrosis [4], kidney fibrosis [5] and cardiovascular disease (including heart fibrosis) [6], likely by stimulating inflammation, the production of toxins and a decrease in beneficial products [4, 6]. A decrease in the microbial production of short-chain fatty acids, such as butyrate, is also thought to be important in disease, because it affects the development of immune regulatory T cells [3, 6]. Because these effects are systemic, they probably also increase the risk of arthrofibrosis, but I’m not aware of research into this. In addition, although supported by animal data, gut microbes have not been proven to increase fibrosis in humans, since it’s not ethical to induce fibrosis.

Figure: Bacteria form complex, networked societies where they communicate with members of their own and other species, including their host, and share their products. Image by K. Usher.

So, by helping your good microbes you’re really helping yourself, and doing this is important for disease management [7]. You and your microbiota are part of the same ecosystem (your body), and encouraging good microbial behaviour can make a big difference to how you feel [7]. But to get the benefits you need the right players in charge of your gut, because with a poor diet you can easily promote microbes that cause significant harm via the production of toxins and compounds that create inflammation and dysregulate the immune system [7]. This is known as dysbiosis [8].


In the world of microbiology, you’re the host. Your gut microbiota consists of “good guys” that are mutualistic and aligned with your health goals, and “bad guys” that are pathogenic, as well as quite a few species that are just along for the ride. Getting the balance right between mutualists and pathogens has a major impact on your immune response and inflammation, and even affects energy and mental health, including anxiety and depression [7, 8]. Luckily, if you treat them right with a high fibre, plant based diet that is low in sugar, and don’t kill them with broad spectrum antibiotics, your mutualistic microbes can prevent pathogenic microbes from taking up residence in your gut by producing antimicrobial compounds, as well as other methods [7].

It seems that we need diverse gut microbiota (many different types) for good mental and physical health, one that is rich in mutualistic species [7]. A lack of diversity and mutualists (dysbiosis) is associated with many diseases including cancer, obesity, type II diabetes, and heart and liver disease [2, 7]. Other associations include poor glucose regulation, high levels of inflammation, high blood pressure and oxidative damage, poor cholesterol control, and increased risk of stroke [2]. Although the gut microbiome has been the focus of intense research there is still a lot of work to do to understand the specific roles of every species, but advances in scientific tools is allowing fast progress [2]. How do you know if you have dysbiosis? Your doctor can have your gut microbiota analysed, and there are now a number of mail order options to do this. Physical signs of dysbiosis include diarrhoea and constipation, and not passing stools regularly (daily) can promote the growth of pathogens [2].

Diet

How do we increase mutualists and microbial diversity in our guts? There are a number of approaches, but probably the most important is a healthy diet [2, 7] that is high in fruit, nuts, whole grains and vegetables and low in animal protein and sugar [6, 7]. Pathogenic microbes love it when you eat a diet that is high in sugar, because the energy from sugar allows them to rapidly reproduce and make toxic compounds that increase inflammation and fibrosis [4]. We need to focus on high fibre plant foods to optimise health, since mutualistic microbes digest fibre to produce beneficial compounds such as butyric and acetic acids that reduce inflammation and regulate the immune system [4]. Most highly processed foods that are common in Western diets are low in fibre and high in sugar, and long-term, a poor diet permits pathogenic microbes to dominate. We can promote mutualistic microbes by consuming at least 30g of fibre a day and slow the growth of pathogens by reducing sugar intake. Dietary fibre should be increased slowly to allow the mutualists to increase in number and break it down - increasing fibre too quickly can have unpleasant effects such as bloating and diarrhoea. For more information, see our blog “Getting adequate dietary fibre will reduce disease”.

Antibiotics

In addition, we should avoid the use of broad spectrum antibiotics as much as we can, since these kill our mutualists and allow pathogens to gain a foothold. Even short-term use of broad spectrum antibiotics can reduce mutualistic bacteria in the long-term [2]. So, if you have a typical sinus infection, cold or flu, the science suggests that you’re better off not taking antibiotics. General practitioners are now advised by their governments not to prescribe antibiotics as a standard treatment for colds and flu in the way that they used to. A range of drugs also affect the composition of your gut microbiota, with some drugs having beneficial effects, and others negative effects. It has been suggested that some of the beneficial effects of metformin derive from the increases in relative abundance of mutualistic gut bacteria, along with an increase in the short-chain fatty acids they produce [2].

Prebiotics

These are supplements that contain soluble fibre that provides food for mutualistic microbes, which can then produce more beneficial compounds. ConsumerLab tested a number of prebiotics and found that the amount of fibre varies greatly. Recommended prebiotics included Hyperbiotics and Bulletproof. I personally take SeaFibre. Increases in fibre consumption should always be slow and gradual to avoid gas and bloating.

Probiotics

Probiotics are “live bacteria that confer a health benefit on the host when provided in suitable proportions” [8]. These microbes may not survive for a long time after consumption, however, this may not be necessary for them to provide health benefits [2]. Bifidobacterium, Lactobacillus and Saccharomyces are beneficial bacteria that have a long history of use in probiotics and are considered safe [2]. However, the use of probiotics is controversial, with some authors stating that they could be detrimental, particularly single-strain products that might dilute the natural microbiota [9]. It may therefore be best to take a product containing multiple species. Probiotics should be used with caution in people who are immunocompromised or severely ill [9]. As always, please consult your doctor before starting probiotics, and if you have a milk allergy watch for milk product warnings. Fermented products containing live microbes such as kefir, kombucha and sauerkraut are a natural way to consume probiotics [8], and have long traditions in many cultures. They can be made at home with care to keep the glassware etc clean and free of contaminants. They typically contain a wide range of microbes and beneficial microbial products.


Figure from Buford et. al. [1]. Prominent health conditions with both biologic age and chronic inflammation as central risk factors. b Prominent health conditions with evidence linking them to gut dysbiosis. Note the similarities between the conditions associated with aging and inflammation and those associated with gut dysbiosis.

There are other methods to alter your gut microbiota, including faecal transplant.


This blog is not medical advice, please consult your doctor before making changes.


References

1. Buford, T. W. (Dis)Trust your gut: the gut microbiome in age-related inflammation, health, and disease. Microbiome5, 80, doi:10.1186/s40168-017-0296-0 (2017).

2. Fan, Y. & Pedersen, O. Gut microbiota in human metabolic health and disease. Nat Rev Microbiol 19, 55-71, doi:10.1038/s41579-020-0433-9 (2021).

3. Zhou, Y., Chen, L., Sun, G., Li, Y. & Huang, R. Alterations in the gut microbiota of patients with silica-induced pulmonary fibrosis. J Occup Med Toxicol 14, 5, doi:10.1186/s12995-019-0225-1 (2019).

4. Ohtani, N. & Kawada, N. Role of the Gut-Liver Axis in Liver Inflammation, Fibrosis, and Cancer: A Special Focus on the Gut Microbiota Relationship. Hepatol Commun 3, 456-470, doi:10.1002/hep4.1331 (2019).

5. Liu, J. R. et al. Gut microbiota-derived tryptophan metabolism mediates renal fibrosis by aryl hydrocarbon receptor signaling activation. Cell Mol Life Sci78, 909-922, doi:10.1007/s00018-020-03645-1 (2021).

6. Xu, H., Yang, F. & Bao, Z. Gut microbiota and myocardial fibrosis. Eur J Pharmacol 940, 175355, doi:10.1016/j.ejphar.2022.175355 (2023).

7. Hou, K. et al. Microbiota in health and diseases. Signal Transduction and Targeted Therapy 7, doi:10.1038/s41392-022-00974-4 (2022).

8. Choudhary, P., Kathuria, D., Suri, S., Bahndral, A. & Kanthi Naveen, A. Probiotics- its functions and influence on the ageing process: A comprehensive review. Food Bioscience 52, 102389, doi:10.1016/j.fbio.2023.102389 (2023).

9. Abid, M. B. & Koh, C. J. Probiotics in health and disease: fooling Mother Nature? Infection 47, 911-917, doi:10.1007/s15010-019-01351-0 (2019).


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