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Antibiotics are drugs that are either bactericidal (i.e. kill bacteria) or bacteriostatic (i.e. inhibit bacterial growth) and are widely prescribed by doctors to treat confirmed or suspected bacterial infections. In fact, roughly 250 million oral antibiotic prescriptions are given out each year in the US, which equates to almost 800 prescriptions per 1000 individuals.
It is well established that antibiotic use causes rapid dysbiosis (i.e. disruption of the healthy commensal microbe communities), and the use of antibiotics, especially in early childhood, is strongly associated with chronic diseases including obesity, autoimmunity, allergies, and inflammatory bowel disease.
Additionally, bactericidal antibiotics actively induce mitochondrial damage leading to increased free radical production, which drives inflammation and tissue damage. We will summarize here the prudent steps one could take during and after antibiotic use to minimize the acute side effects and long-term damage to the gut microbiome.
There are two major categories of bacteria: Gram positive and Gram negative, both of which are found within the microbiota. Data generated using more recent technology suggests that the split may actually be closer to 80% Gram positive, e.g. Lactobacillus, and 20% Gram negative, e.g. E. Coli.
The type of antibiotic administered dictates whether Gram-positive, Gram-negative, or both Gram-positive and Gram-negative bacteria will be affected. Antibiotics that selectively target one group of bacteria are known as narrow spectrum, whereas antibiotics that kill all bacteria indiscriminately are referred to as broad spectrum.
This distinction is crucial because the use of narrow-spectrum antibiotics, whenever possible, partially mitigates the collateral damage inflicted on the microbiome by antibiotic exposure.
Conversely, the overuse of broad-spectrum antibiotics results in not only deleterious effects on the commensal microbial communities in and on the body, but is also largely responsible for a phenomenon known as antibiotic resistance.
Antibiotic resistance occurs when bacteria acquire genes that allow them to either break down antibiotic molecules or prevent the antibiotic from entering into cells. In this way, the bacteria become impervious to the antibiotic being used. This gene can be passed on to other bacteria, and ultimately protect the population from death or growth inhibition.
Antibiotic resistance in bacteria is driven by 1) over-prescription of antibiotics which increases the probability that resistance genes will arise and 2) the use of broad-spectrum antibiotics in patients who could have been treated with narrow-spectrum antibiotics.
The table below outlines the commonly prescribed broad- and narrow-spectrum antibiotics and their uses.
Because most narrow-spectrum antibiotics do not readily affect bacteria within the microbiome, these drugs are far less damaging to the gut and overall health.
However, depending on the narrow-spectrum antibiotic being used, the populations of some commensal species may be negatively impacted. To combat this, individuals should prioritize the consumption of prebiotics that support the growth of the key genus of bacteria known as Bifidobacteria.
Bifidobacteria are Gram-positive anaerobes that live in the colon. They are responsible for breaking down indigestible carbohydrates into small molecules that feed other key species of bacteria in the gut. In this way, focusing on optimization of this foundational Bifidobacteria level is an effective strategy to rebuild the microbiome as a whole.
To support Bifidobacteria populations in the gut, prioritize consumption of the following:
The human milk oligosaccharide (HMO), e.g. 2’-fucosyllactose (2’-FL), is very effective in supporting the growth of bifidobacteria since the digestion of 2’-FL requires a special set of enzymes and genes, which only exist in certain strains of bifidobacteria and Akkermansia.
Additionally, the consumption of fermented foods such as sauerkraut, kimchi, and kombucha have been shown to further bolster microbial diversity in the gut and thereby support a healthy and resilient microbiome.
Given the lesser impact of narrow-spectrum antibiotics on the microbiota, there are no additional considerations in the post-antibiotic setting. Instead, one should prioritize the consumption of prebiotic foods mentioned above in the weeks following cessation of antibiotic use to ensure a faster rebuild of the microbiome.
Broad-spectrum antibiotics cause a great deal of disruption to the microbiome as they are unable to specifically target the pathogen causing infection.
As a result, the microbiome is severely depleted during a course of broad-spectrum antibiotics. For this reason, individuals should avoid consuming foods high in indigestible carbohydrates like insoluble fibers, soluble fibers, and resistant starches as they will not be effectively broken down in the absence of bacteria and, accordingly, may cause gastrointestinal distress.
Instead, the diet should consist of easily digested foods that provide key nutrients to the intestines. These foods include: fully cooked meat, bone broth, berries, and citrus. The bone broth is rich in amino acids which serve as the primary fuel source for the intestines, while the polyphenols in berries and citrus help to mitigate gut inflammation in the absence of the anti-inflammatory molecules normally produced by beneficial microbes.
One such anti-inflammatory molecule is the short chain fatty acid butyrate. Butyrate is the primary fuel source for colon cells and also modulates immune cell function to promote the production of anti-inflammatory factors and inhibit the production of inflammatory factors.
Bifidobacteria bolster levels of butyrate by secreting metabolites that feed butyrate-producing species. During broad-spectrum antibiotic treatment, populations of both Bifidobacteria and the butyrate producers become depleted. Therefore, butyrate production is greatly diminished.
To combat this, consumption of exogenous ketones and/or adherence to a ketogenic diet may be a good approach to protect the colon from energy deprivation in the absence of butyrate. This is because the primary ketone body, 3-hydroxybutyrate, can be used by the colon cells in lieu of butyrate to power energy production.
Moreover, like butyrate, 3-hydroxybutyrate also serves as an immune modulator and confers anti-inflammatory effects in the body. Therefore, maintaining some level of ketosis, be it through diet or supplementation, during broad-spectrum antibiotic use can compensate for the negative effects on the microbiome by providing an alternative to butyrate in the body.
In addition, gut bacteria can produce vitamin K and vitamin B, like folic acid. The depletion of gut microbes may lead to deficient production of vitamin K and folate in the gut; therefore, folate rich foods and vitamin K rick foods should also be added into the diet. Vitamin K-rich foods include kale, spinach, collard, etc. Foods high in folate include beef liver, dark, leafy greens, legumes, whole grains, and eggs.
Because the microbiome is largely depleted during broad-spectrum antibiotic use, the focus in the post-antibiotic setting is to restore both the amount and diversity of bacteria in the gut.
The extent to which the microbiome is affected by antibiotic use depends on the type of antibiotic administered, with broad-spectrum antibiotics eliciting the most damage. During and after use of narrow-spectrum antibiotics, consuming foods to feed your gut bacteria, can help prevent deleterious effects on the microbiome.
Following broad-spectrum antibiotic use, the gradual introduction fermented foods, prebiotics, and diverse sources of fibers facilitates the repopulation of the gut and diversification of the microbes therein.
Author:
Dr. Alexis Cowan, a Princeton-trained PhD specializing in the metabolic physiology of nutritional and exercise interventions.
Follow Dr. Cowan on Instagram: @dralexisjazmyn
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