Ecological and Evolutionary responses to Antibiotic Treatment in the Human Gut Microbiota

Abstract

The potential for antibiotics to affect the ecology and evolution of the human gut microbiota is well recognised and has wide-ranging implications for host health. Here, we review the findings of key studies that surveyed the human gut microbiota during antibiotic treatment. We find several broad patterns including the loss of diversity, disturbance of community composition, suppression of bacteria in the Actinobacteria phylum, amplification of bacteria in the Bacteroidetes phylum, and promotion of antibiotic resistance. Such changes to the microbiota were often, but not always, recovered following the end of treatment. However, many studies reported unique and/or contradictory results, which highlights our inability to meaningfully predict or explain the effects of antibiotic treatment on the human gut microbiome. This problem arises from variation between existing studies in three major categories: differences in dose, class, and combinations of antibiotic treatments used; differences in demographics, lifestyles, and locations of subjects; and differences in measurements, analyses, and reporting styles used by researchers. To overcome this, we suggest two integrated approaches: (i) a top-down approach focused on building predictive models through large sample sizes, deep metagenomic sequencing, and effective collaboration; and (ii) a bottom-up reductionist approach focused on testing hypotheses using model systems.

Collateral Damage in the Human Gut Microbiome - Blastocystis Is Significantly Less Prevalent in an Antibiotic-Treated Adult Population Compared to Non-Antibiotic Treated Controls

“…These data are important, as they are linked to how microbiomes are affected by and recover following antibiotic perturbation. However, there is considerable interindividual variation in both the effect of antibiotics on bacterial populations in the gut microbiome, as well as their ability to recover, and this variability in response is due to a range of factors including initial microbiota composition (Dethlefsen and Relman, 2011;Ng et al, 2019;Chng et al, 2020;Pennycook and Scanlan, 2021). This, taken together with the lack of significant effect of treatment number, and time since treatment, on prevalence rates, as well as the fact that there are some positive cases within the ABX+ group, suggests that antibiotic treatment also has differential effects on Blastocystis carriage at the individual level.…”

“…Antibiotics are life-saving medicines that play a central role in the fight against infectious disease as well as facilitating many medical practices such as surgeries and chemotherapy (Hutchings et al, 2019). However, antibiotic treatments can drive the rapid loss of non-target, and phylogenetically and functionally diverse, microorganisms associated with the human body (Dethlefsen and Relman, 2011;Korpela et al, 2016;Elvers et al, 2020;Ramirez et al, 2020;Maier et al, 2021;Pennycook and Scanlan, 2021). The potential negative effects of this socalled "collateral damage" on the human microbiome has myriad implications for host health and has been attributed, in part, to the rise of many chronic immunological and metabolic disorders such as obesity and diabetes (Bailey et al, 2014;Boursi et al, 2015;Saari et al, 2015;Bejaoui and Poulsen, 2020).…”

“…Moreover, in some scenarios, antibiotic administration can lead to extreme perturbations and loss of microbiota predisposing individuals to expansion of and/or invasion by opportunistic pathogens resulting in potentially fatal infections such as Clostridioides difficile associated disease (CDAD) (Spencer, 1998;Baxter et al, 2008). Accordingly, an understanding of how antibiotics affect the ecology and evolution on the human gut microbiota has been the subject of a multitude of different in vitro, in silico and in vivo studies (Dethlefsen and Relman, 2011;Candon et al, 2015;Shaw et al, 2019;Chng et al, 2020;Ramirez et al, 2020;Pennycook and Scanlan, 2021).…”

“…Resulting data shows that for some individuals, bacterial communities can apparently fully recover to preintervention states and exhibit resilience, whereas in other individuals, the bacterial community remains altered from its base-line status over the longer-term (Dethlefsen and Relman, 2011;Roodgar et al, 2021). This observed inter-individual variation in response to treatment is likely due to the class of antibiotic used, the dose and frequency of dose, the initial composition of the microbiota as well as other host and environment related factors (Ng et al, 2019;Chng et al, 2020;Pennycook and Scanlan, 2021;Rashidi et al, 2021). Crucially, recent studies have shown that antibiotics can alter the intestinal mycobiome (fungal component of the community) (Seelbinder et al, 2020) and virome (Goŕska et al, 2018;Haak et al, 2021), which indicates that the collateral effects of antibiotics on the gut microbiota extend beyond the bacterial fraction of the community.…”

Bifidobacterium animalis subsp. lactis BB-12 Protects against Antibiotic-Induced Functional and Compositional Changes in Human Fecal Microbiome

“…SCFAs are essential for gastrointestinal health and are absorbed by colonic epithelial cells, and stimulate Na + -dependent fluid absorption [2], thereby conserving energy, Na + , and fluid. The administration of antibiotics impacts gastrointestinal tract homeostasis, and is associated with an overall reduction in the numbers and diversity of the gut microbiota, decreased SCFA production, accumulation of luminal carbohydrate, subsequent pH changes, decreased water absorption, and, potentially, antibiotic-associated diarrhea (AAD) [3][4][5][6][7][8][9][10]. However, the etiology of AAD is not fully elucidated.…”