The impact of antibiotics

We know antibiotic treatment has an effect on the microbiota but what about the immune system? Here, Nutritional Therapist, Adrienne Benjamin, offers her perspective.

What are the key factors that can affect a person’s immune system?

The immune system is affected by a wide range of external factors, including genetics, infection, stress, a diet high in sugar and alcohol, lack of sleep, smoking, lack of exercise and poor hygiene. Much of this external effect, however, can be attributed to the impact of these activities on the internal gastro-intestinal tract (GIT) and the gut microbiome. [1,2,3]
The GIT is the main site of interaction between our immune system and both beneficial and pathogenic microorganisms, and the development and function of the immune system depend on these interactions. [4] The GIT is a single layer of cells, which presents a dynamic structure to recognise commensal bacteria and to limit pathogens from entering the body. The evidence suggests that the commensal flora exerts an anti-inflammatory and immune influence, providing essential nutrients, metabolising indigestible compounds, defending against pathogens and supporting the intestinal architecture. [5,6]

The microbiota is established at birth when bacteria are transmitted from mother to baby, and during the first year of life as the baby is exposed to different external factors. The diversity and number of bacteria in the microbiota increases over this period to drive the development of the immune system and ultimately ensure that the bacteria are recognised by the immune system as ‘self’. [7] As well as the mode of birth, a number of factors have been shown to influence this development, including prematurity, hygiene, breastfeeding, [8,9] and antibiotic exposure. [10]

The gut microbiota interacts with the immune system and provides signals to promote the growth of immune cells and the normal development of the immune function. [11] Improper training of the immune system by the microbiota is known to result in immune-mediated diseases, including susceptibility to influenza, retrovirus transmission and more serious diseases, [12] such as colon cancer and auto-immune demyelination. [13]

Antibiotic effect

Looking at antibiotics, what impact can they have on the gut, and consequently, the immune system?

Our microbiome is exposed to high numbers of antibiotics, both medicinally and through their use in farm animals. Antibiotics are the most common medications prescribed for children and studies suggest an association between early antibiotic use and the development of disease in adulthood. [14]

Evidence shows that antibiotics can very quickly lead to dysbiosis in the gut microbiota, with broad-spectrum antibiotics showing an effect on the numbers of around a third of the bacteria in the gut, causing fast and significant reduction in their quantity, diversity and symmetry. Once antibiotic treatment is complete, the microbiota may show some resilience and return to a composition similar to that seen prior to the antibiotics, but often this is not a complete recovery to the original state. [15]

As the established gut microbiome reshapes following antibiotic use, resistance to colonisation is reduced, enabling foreign microbes to potentially overtake the commensal bacteria and cause permanent changes in the structure of the microbiota [16] hence affecting the immune system. These changes are likely to increase and become more permanent following repeated antibiotic exposure.

What signs can a person expect if antibiotics have impacted their immune system?

Investigations into the effects of antibiotics on the gut microbiota have shown that antibiotics affect the way that the gut microbiota interacts with the host and change the effectiveness of both the innate and adaptive immune responses. This has been shown to result in increased susceptibility to infections, elevated systemic inflammation, dysregulated metabolism and the establishment of antibiotic-resistant bacteria. [17]

As well as a reduction in immunity, the changes in the microbiome can lead to a wide variety of gut-related health issues, such as gas and bloating, diarrhoea, gastritis, irritable bowel syndrome (IBS) and can ultimately result in atopic, inflammatory and autoimmune diseases, such as allergies, asthma, necrotising enterocolitis and inflammatory bowel disease (IBD). [18]

Is there anything people can do to support their immune system during a course of antibiotics?And what about afterwards?

If we consider that balanced gut microbiota is key to supporting immunity, and antibiotics detrimentally affect the microbiome, it is imperative to support this bacterial balance, both during and immediately following antibiotic intake.

Investigations into the use of probiotics to support the microbiota have shown that probiotic strains can support antibiotic therapy by reducing adverse effects, improving the function of the antibiotics and enhancing immunity.’ [19]

Clinical research into the use of probiotics alongside and following antibiotics at Addenbrooke’s Hospital, in Cambridge, showed that supplementation with Lab4 probiotics reduced the overgrowth of bad bacteria in the regrowth of the microflora following antibiotic therapy [20] and significantly reduced the incidence of antibiotic resistance to enterococci [21] (one of the most ‘resistance-prone’ groups of hostile bacteria within the microbiota).

Nutritional intervention

Dietary wise, what would you recommend to support the immune system, especially after a course of antibiotics? And from a supplement perspective, what would you recommend and why?

The importance of diversity of bacterial strains suggests that the composition of the whole microbiome influences a balanced immune response [22] and foods that include multiple types of bacteria are likely to be most effective in supporting the re-establishment of a healthy microbiome. These include some live yoghurts and fermented and pickled foods, such as sauerkraut, kefir and kimchi.
A daily multi-strain probiotic supplement can help by providing very high numbers of friendly live bacteria (ensure it is backed by clear and efficacious research).

Prebiotic fibres can also help to stimulate the growth and activity of certain bacterial groups [23] and can be found in fibrous vegetables, such as broccoli (particularly the stalks), leeks and artichokes, as well as in dietary supplements, such as inulin and oligosaccharides.

The pathogenic bacterial strains use sugar as their main source of fuel, so it is useful to limit sugar intake and to avoid the standard western-style diet. Instead, following a high-fibre diet that includes adequate water intake and a balance of macro- and micro-nutrients to support the symbiotic gut bacteria can support balance and hence immunity. [24]

Finally, outside of the microbiome, specific nutrients have been shown to support the immune system and may be worth supplementing alongside a vegetable- and fruit-rich diet. These include vitamins A, B6, B12, C and D, copper, folate, iron, selenium and zinc. 25]
Adrienne Benjamin
Nutritional Therapist and NLP Practitioner, having completed her Nutritional Therapy degree at CNELM in 2013. Prior to studying nutrition, Adrienne achieved a degree in business and an MBA and had more than 12 years of experience working in the media industry in senior marketing positions. Adrienne is now Marketing Manager and Nutritionist at ProVen Probiotics.

For references, please visit: www.ihcan-mag.com/References

[1] Voigt RM et al (2014) Circadian Disorganization Alters Intestinal Microbiota. PLoS ONE 9(5):e97500. Doi:10.1371/journal.pone.0097500

[2] Konturek PC et al (2011) Stress and the gut: pathophysiology, clinical consequences, diagnostic approach and treatment options. J Physiol Pharmacol 62(6):591-599

[3] Conlon MA & Bird AR (2015) The Impact of Diet and Lifestyle on Gut Microbiota and Human Health. Nutrients 7(1):17-44

[4] Macpherson AJ & Harris NL (2004) Interactions between commensal intestinal bacteria and the immune system. Nat Rev Immunol 4:478-485

[5] MacDonald TT & Monteleone G (2005) Immunity, Inflammation, and Allergy in the Gut. Science 307:1920-1925

[6] Round JL & Mazmanian SK (2009) The gut microbiome shapes intestinal immune responses during health and disease. Nat Rev Immunol 9(5):313-323

[7] Del Chierico F et al (2015) Phylogenetic and Metabolic Tracking of Gut Microbiota during Perinatal Development. PLoS ONE; DOI:10.1371/journal.pone.0137347

[8] Backhed F et al (2015) Dynamics and stabilization of the human gut microbiome during the first year of life. Cell Host Microbe 17:690-703

[9] Tannock GW et al (2013) Comparison of the compositions of the stool microbiotas of infants fed goat milk formula, cow milk-based formula, or breast milk. Appl Environ Microbiol 79:3040-8

[10] Hussey S et al (2012) Parenteral antibiotics reduce bifidobacteria colonization and diversity in neonates. Int J Microbiol doi: 10/1155/2011/130574

[11] Chow J et al (2010) Host-Bacterial Symbiosis in Health and Disease. Adv Immunol 107:243-274

[12] Petersen C & Round JL (2014) Defining dysbiosis and its influence on host immunity and disease. Cell Microbiol 16(7):1024-1033

[13] Clemente JC et al (2012) The Impact of the Gut Microbiota on Human Health: An Integrative View. Cell 148: 1258-1270

[14] Vangay P et al (2015) Antibiotics, Pediatric Dysbiosis, and Disease. Cell Host Microbe 17(5):553-564

[15] Dethlefsen L & Relman DA (2011) Incomplete recovery and individualized responses of the human distal gut microbiota to repeated antibiotic perturbation. PNAS 108(1):4554-4561

[16] Clemente JC et al (2012) The Impact of the Gut Microbiota on Human Health: An Integrative View. Cell 148: 1258-1270

[17] Francino MP (2016). Antibiotics and the Human Gut Microbiome: Dysbioses and Accumulation of Resistances. Front Microbiol 6:1543

[18] Francino MP (2016). Antibiotics and the Human Gut Microbiome: Dysbioses and Accumulation of Resistances. Front Microbiol 6:1543

[19] Reid G (2006) Probiotics to prevent the need for, and augment the use of, antibiotics. Can J Infect Dis Med Microbiol 17(5):291-295

[20] Plummer SF et al (2005) Effects of probiotics on the composition of the intestinal microbiota following antibiotic therapy. Int J Antimicrob Agents 26:69-74

[21] Madden JAJ et al (2005) Effect of probiotics on preventing disruption of the intestinal microflora following antibiotic therapy: A double-blind placebo-controlled pilot study. Int Immunopharmacol 5:1091-1097

[22] Petersen C & Round JL (2014) Defining dysbiosis and its influence on host immunity and disease. Cell Microbiol 16(7):1024-1033

[23] Petersen C & Round JL (2014) Defining dysbiosis and its influence on host immunity and disease. Cell Microbiol 16(7):1024-1033

[24] Conlon MA & Bird AR (2015) The Impact of Diet and Lifestyle on Gut Microbiota and Human Health. Nutrients 7(1):17-44

[25] http://ec.europa.eu/food/safety/labelling_nutrition/claims/register/public/?event=search

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