Whilst antibiotics absolutely save lives, there has been a long-standing culture of over-prescription. This has led to problems that we are now experiencing such as antibiotic resistance and also has implications for our own microbiome.
Our digestive system is coated with a layer of microbes which play an essential role in many aspects of health including immunity, digestion, cognitive function, weight management and inflammation. This layer or biofilm, made up of a fine balance of different bacteria, fungi, protozoa and viruses and their collective genetic material, is referred to as the microbiome. A healthy microbiome consists of a high diversity of micro-organisms living in homeostasis without one species dominating. Disruption to the finely balanced microbiome can be detrimental to health and changes can persist for a long time1.
Studies have shown that there is a decrease in bacterial diversity following antibiotic treatment. As most of the antibiotics available on the market have a broad spectrum of action, they affect not only harmful bacteria, but also the healthy ones. In a study of a large cohort of Finnish children, the administration of antibiotics (macrolides) was shown to induce long-term alterations to the composition of the microbiota, particularly a reduction of Actinobacteria (mainly Bifidobacteria), Firmicutes (mainly Lactobacilli) and total bacterial diversity, as well as an increase in relative abundance of Bacteroidetes and Proteobacteria2. However other types of antibiotics, were demonstrated to have less of an effect on microbiome diversity; which seems to be very dependent on both the individual, their microbiome and the type of antibiotic used3,4.
Short-term alterations to the gut microbiota due to antibiotics have been extensively investigated. In contrast, only a few recent studies have addressed long-lasting changes to the gut microbiota after antibiotic treatment. As mentioned above drug-related factors and host-related factors affect the impact of antibiotics on the composition of the human gut microbiota. In studies which investigated persistence, the longest duration of changes was reported after treatment with ciprofloxacin (one year), clindamycin (two years) and clarithromycin plus metronidazole (four years)5.
In addition, it has been shown that antibiotics cause further disruption to the gut. One of the ways they do this is by damaging the gastrointestinal (GI) epithelium, which may be in part a result of disruption to the microbiome. Many antibiotics are associated with a decrease in butyrate or butyrate-producing bacteria, this is a short chain fatty acid utilised by the intestinal cells (i.e. enterocytes that line the GI tract) for fuel and to aid repair and rejuvenation4,5.
It has also been demonstrated that bacterial translocation (i.e. the passage of bacteria through the gut lining and into the circulation) increases following a single dose of antibiotics and that this is associated with increased inflammation. This is partly due to the increase in gut permeability (i.e. leaky gut) but also results from decreased microbial signals delivered to colonic goblet cells, which are immune cells found in the colon, and therefore goblet cells failing to prevent antigen passing across the gut lining. These findings revealed that bacterial translocation as a result of alterations in the intestinal microflora may provide a link between increasing antibiotic use and the increased incidence of inflammatory disorders6.
Antibiotic associated diarrhoea (AAD) is a common adverse effect of systemic antibiotic treatment. AAD occurs in 5% to 39% of patients and can happen up to two months after the end of treatment. Any type of antibiotics can cause AAD. The symptoms range from mild and self-limiting diarrhoea to severe diarrhoea, the latter particularly where post-antibiotic infections with Clostridium difficile occur7.
Supporting the Microbiome
As microbiome disturbance is considered to contribute to many different conditions, including obesity, cardiovascular disease, cognitive dysfunction and immune disturbances (the composition of the microbiota is a factor in the development of autoimmune diseases), it is important to support the microbiome during and after antibiotic treatment.
Research demonstrates that the microbiome can be modulated by consumption of fibre and prebiotic foods (which provide fibre that is fermented by gut bacteria); probiotic foods (fermented foods which naturally contain live bacteria); and live bacteria supplements.
Fibre and prebiotic foods
Intervention studies in humans have shown that dietary fibre and wholegrain intake increases gut bacterial diversity. Low-fibre intake in Western societies is purported to be a driver in the depletion of the human gastrointestinal microbiota and subsequent increases in chronic non-communicable diseases, such as obesity, cardiovascular disease, type 2 diabetes, and colon cancer1.
One dietary strategy for modulating the microbiota is consumption of specific fibre known as prebiotics that can be metabolised by microbes in the gastrointestinal tract. Human digestive enzymes are not able to digest most complex carbohydrates and plant polysaccharides. Instead, these polysaccharides are metabolised by microbes which generate short-chain fatty acids (SCFAs), including acetate, propionate, and butyrate1,8.
Prebiotics were originally defined in 1995 by Gibson and Roberfroid as “a non-digestible food ingredient that beneficially affects the host by selectively stimulating the growth and/or activity of one or a limited number of bacteria in the colon, and thus improves host health.”
In 2004, the definition of prebiotic was updated to add three criteria:
- Resistant to gastric acidity and hydrolysis by mammalian enzymes and gastrointestinal absorption
- Fermented by intestinal microbiota
- Selectively stimulate the growth and/or activity of intestinal bacteria associated with health and wellbeing
Different structures of prebiotic fibres support different varieties of bacteria within the gut; polysaccharide chain length and the branching of fibre influences the ability of specific bacteria to ferment it as this will depend on the enzymes they are able to produce. For example, many bacteria can ferment short chain fructo-oligosaccharides (FOS), and Bifidobacterium, Bacteroides, Faecalibacterium, Lactobacillus, and Roseburia can ferment oligofructose (a type of FOS). However, relatively few can utilise long-chain fructans. Bacterial species within the same genre also have varying abilities to degrade fibre sources. For examples, B. bifidum can grow on FOS in vitro, but not on inulin. Branching of fibre molecules also differentially impacts the location of fermentation within the gastrointestinal tract.
There are many sources of prebiotic foods, most of the thinking now is that to support diversity in the gut you need diversity in the diet. A wide variety of plant-based foods, particularly vegetables, provides a wide variety of prebiotics. One challenge is to ensure that you consume 50 different types of food every week. This will provide a range of prebiotics and encourage a diverse microbiome. Download the 50 Foods Challenge sheet below:
Sources of prebiotic foods
There are many sources of prebiotics and as mentioned above consuming a large number and variety of vegetables will provide a range of different prebiotics. However, foods identified as excellent sources of prebiotics include: asparagus, sugar beet, garlic, chicory, onion, Jerusalem artichoke, barley, tomato, rye, soybean, peas, legumes, seaweeds, microalgae and human breast milk. Furthermore, foods rich in polyphenols such as olives, olive oil, dark chocolate and coffee also have prebiotic effects.
The polyphenol ellagic acid, found in pomegranate supports the growth of Akkermansia municiphila, a species of bacteria associated with lean body types9.
Foods were traditionally fermented to enhance flavour and preserve them, thus providing food over the winter months. Now the full benefits of fermented food are being realised. The fermentation process supports the growth of a wide number of bacteria. Therefore, fermented foods are natural sources of live bacteria and are often known as probiotic foods. Fermented foods have demonstrated the ability to modulate the gastrointestinal microbiota, redress dysbiosis (which refers to overgrowth of undesirable species), and enhance human health10.
An example of this is a study that showed the consumption of kimchi and other fermented vegetables was correlated with reduced incidence of asthma and atopic dermatitis in Korean adults. In another study, consumption of fermented soybean foods was associated with a reduced risk of type 2 diabetes and high blood pressure among Japanese adults.
Sources of probiotic foods
Any food which has been fermented can be considered to be probiotic, however the most utilised probiotic foods include kombucha (fermented tea), kefir, sauerkraut, kimchi, miso, live unpasteurised yoghurt and pickles. It is worth noting however that some of the foods which are available in the supermarket may have been pasteurised or not even fermented in the first place and therefore will not contain live bacteria. So, it is best to choose live, and preferably from an organic source; a health food shop would be a good place to start. You can also ferment your own foods.
Live bacteria supplements or probiotics
Probiotics are supplements which contain live bacteria that have been demonstrated to elicit an effect on the gut and microflora. The core benefit of probiotics is derived from the contribution they make to the maintenance of a balanced microbiota; therefore, by creating a favourable gut environment, they have been shown to elicit favourable effects on the health of the gut and the immune system. Probiotics have been shown to positively modulate gut microbiota composition by increasing the diversity of the bacteria population and supporting the integrity of the gut epithelium barrier, i.e. protecting against leaky gut11.
The positive effect of probiotics on gut health in a variety of conditions (antibiotic-associated and infectious diarrhoea, irritable bowel syndrome, necrotising enterocolitis, etc.) has been evaluated by a number of randomised controlled clinical trials11.
In a study looking at antibiotic associated diarrhoea, (AAD) results suggested that probiotic use may be beneficial in the prevention of AAD among outpatients and that the use of probiotics appears safe. The overall pooled results showed that the use of probiotics produced a statistically significant reduction in the incidence of AAD7.
As discussed, antibiotics can disrupt the gut microflora and these effects can persist over a long period of time. Therefore, it is useful to support a healthy microbiome during and after antibiotic treatment to mitigate these adverse effects.
- The gut microflora play an essential role in maintaining health. Studies have demonstrated their importance for immunity, vitamin synthesis, normal digestive function as well as associated reduction in the risk of obesity, cardiovascular disease and cognitive decline, to name a few.
- Antibiotics elicit a negative effect on the microbiome which can lead to dysbiosis (overgrowth of undesirable species), leaky gut, increased inflammation and also a higher likelihood of antibiotic resistance. In addition, some individuals prescribed antibiotics suffer with antibiotic associated diarrhoea.
- Disruption to the microbiome by the use of antibiotics has been shown to increase gastro-intestinal permeability (or leaky gut) and therefore allow the passage of bacteria across the gut epithelial barrier, which can trigger inflammation. This is thought to explain the association between antibiotic use and inflammatory diseases.
- Fibre and prebiotic foods have been shown to support diversity of the microbiome and therefore should be considered as part of a healthy diet and also during and after antibiotic use. Consuming a wide variety of different foods, particularly of vegetables, is important as a diverse diet supports a diverse microbiome. Aim to consume at least 50 different types of food in a week (bread and pasta count as one type as they are both wheat; on the other hand, a red onion and white onion count as two types).
- Probiotic foods contain live bacteria and are made by fermentation. Consumption of fermented foods such as kefir, kombucha, kimchi, miso, sauerkraut and live natural yoghurt has been shown to support a healthy microbiome and is associated with a reduced risk of many non-communicable diseases.
- Research has shown live bacteria supplements reduce incidence of antibiotic associated diarrhoea. They have also been shown to support the health of the gut, immunity and promote a healthy microbiome.
- Holscher HD. Dietary fiber and prebiotics and the gastrointestinal microbiota. Gut Microbes. 2017;8(2):172-184. doi:10.1080/19490976.2017.1290756
- Korpela K, Salonen A, Virta LJ, Kekkonen RA, Forslund K, De Vos WM. ARTICLE Intestinal microbiome is related to lifetime antibiotic use in Finnish pre-school children. Nat Commun. 2016;7. doi:10.1038/ncomms10410
- Ianiro G, Tilg H, Gasbarrini A. Antibiotics as deep modulators of gut microbiota: Between good and evil. Gut. 2016;65(11):1906-1915. doi:10.1136/gutjnl-2016-312297
- Criscuolo D, Srl G, Dominique Dubois IJ, et al. Obesity: A New Adverse Effect of Antibiotics? 2018. doi:10.3389/fphar.2018.01408
- Zimmermann P, Curtis N. The effect of antibiotics on the composition of the intestinal microbiota – a systematic review. J Infect. October 2019. doi:10.1016/j.jinf.2019.10.008
- Knoop KA, McDonald KG, Kulkarni DH, Newberry RD. Antibiotics promote inflammation through the translocation of native commensal colonic bacteria. Gut. 2016;65(7):1100-1109. doi:10.1136/gutjnl-2014-309059
- Blaabjerg S, Artzi DM, Aabenhus R. Probiotics for the prevention of antibiotic-associated diarrhea in outpatients—A systematic review and meta-analysis. Antibiotics. 2017;6(4). doi:10.3390/antibiotics6040021
- Valdes AM, Walter J, Segal E, Spector TD. Role of the gut microbiota in nutrition and health. BMJ. 2018;361:36-44. doi:10.1136/bmj.k2179
- Henning SM, Summanen PH, Lee RP, et al. Pomegranate ellagitannins stimulate the growth of Akkermansia muciniphila in vivo. Anaerobe. 2017;43:56-60. doi:10.1016/j.anaerobe.2016.12.003
- Rezac S, Kok CR, Heermann M, Hutkins R. Fermented foods as a dietary source of live organisms. Front Microbiol. 2018;9(AUG). doi:10.3389/fmicb.2018.01785
- Azad MAK, Sarker M, Li T, Yin J. Probiotic Species in the Modulation of Gut Microbiota: An Overview. Biomed Res Int. 2018;2018. doi:10.1155/2018/9478630
If you have questions regarding the topics that have been raised, or any other health matters, please do contact me (Helen) by phone or email at any time.
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Helen Drake and the Cytoplan Editorial Team