That causes environmental overshoot of microbial ecosystems---extinction.

Ecological alterations of the microbiota (dysbiosis), occasionally with clinically intestinal complications, ranging from mild to severe, were described from the early stages in the use of antibiotics (Haenel 1961). The most important was the selection of harmful resistant organisms. Classical examples are enterococcal bacteremia during therapy with third-generation cephalosporins, or more recently the potentially lethal pseudomembranous colitis resulting from the selection of Clostridium difficile (Smits et al. 2016) frequently associated with the use of broad-spectrum antibiotics, particularly those influencing the predominant anaerobic populations.

Alterations of the microbiota are generally restored by surviving minorities and by the organisms of the surrounding human environment. In hospital, nursing homes, or in conditions of limited sanitation in low-income countries, particularly involving water environments (Baquero et al. 2008), restoration might involve the acquisition of antibiotic-resistant populations, substituting (without the need of antibiotic exposure) the old susceptible ones (Schwartz et al. 2020). The final effect is that antibiotic-resistant bacteria are increasingly integrated as “normal members of the microbiota,” and the long-term consequences of such replacements and the creation of a novel microbiota architecture remain unknown. This might be harmful, influencing inflammatory bowel diseases, allergies, asthma, obesity, diabetes, cardiovascular disease, neurobehavioral disorders, and eventually involving alterations in host immunity (Zhang and Chen 2019). Note that resistant populations (by either intrinsic or acquired antibiotic resistance) are poorly affected (resilient) by new antibiotic exposure, facilitating long-term colonization and host adaptation. The invasion of food animals by antibiotic-resistant bacteria and the increasing possibilities of human-animal microbiome coalescence (merging) might contribute to the evolution towards abnormal microbiomes with unpredictable consequences (Baquero et al. 2019).

Antibiotic resistance modifying bacterial population biology and evolutionary biology

Antibiotics exert multi-level selection, that is, they independently select for particular genes, insertion sequences, integrons, transposons, plasmids, integrative-conjugative elements, and also for particular clones and clonal complexes within species, species, genus, and complex microbial communities (Baquero et al. 2013). The effect results in alterations in the relative abundance and diversity of these evolutionary entities. Considering that in a world without anthropogenic antibiotics the microbial (multilevel) entities tend to keep their historical co-evolutionary selected compositions inside their hosts, the disturbance of such equilibrium by antimicrobial agents might result in inadvertent risks. Of course, antibiotic selection of antibiotic-resistant bacteria implies the selection not only of the resistance genes, but of all the mobile genetic elements to which they are associated. In fact, the release in the environment of antibiotics, among other anthropogenic contaminants, increases the local density of harmful antibiotic resistance genes and also mobile genetic elements (Knapp et al 2010; Wright et al. 2008; Gillings 2014). Increased density of mobile genetic elements implies an acceleration of the bacterial evolutionary rate (Souque et al. 2021). In other words, antibiotic resistance might significantly increase the density of tools involved in microbial genetic interactions, once more with unpredictable consequences in shaping bacterial evolutionary trajectories that might influence human and animal health (Baquero et al. 2021a, 2021b).

Antibiotic resistance and the planet microbiosphere

Human health is fully dependent on the health of the biological systems determining the main features of our environment. Antibiotics have historically been and are still constantly released into the environment; it has been estimated that the global annual production of antibiotics reaches 100–200 thousand tons, and one billion tons have been produced since 1940 (Serwecińska 2020), and many of them remain biologically active during extended periods of time. Considering that antibiotics can select antibiotic populations with relative decreases in susceptibility at concentrations of nanograms/ml, and/or interfere at such concentrations with the semiotic network of natural antibiotics, acting as interbacterial signaling agents (Linares et al. 2006), we can expect an effect on the natural microbiosphere. Possible ecological functional disturbances caused by the release of the antibiotics in the environment might include critical aspects for life, as oxygen production, nitrogen transformation, methanogenesis, or sulfate reduction. For instance, Cyanobacteria contribute with more than 25% of oxygen production and carbon dioxide fixation in Earth. Cyanobacteria are susceptible to most antibiotics and contain mobile genetic elements that might facilitate capture of antibiotic resistance, but how this might influence fitness and physiology of these organisms is unknown (Dias et al 2019; Hernando-Amado et al. 2019). There is also an effect of environmental antibiotics on the bacterial components of the rhizosphere, essential for nitrogen fixation and plant health, on the biology of Protistan and protistan consumers in the soil, as well as the microbes-nematode interactions. It is known that low antibiotic exposure influences plant biology affecting plant germination, biomass allocation, and diversity (Minden et al 2017). We can also expect harmful effects on insect vital endosymbionts (Koga et al. 2007), and probably microbe-originated cellular organelles mitochondria and chloroplasts could evolve to antibiotic resistance (Perasso 1974; Wang et al. 2015). A possible risk is the substitution of part of the key antibiotic-susceptible natural species by other intrinsically antibiotic-resistant organisms or selected variants, influencing primary producers, and potentially biogeochemical cycles in the Earth’s surface systems. This certainly will approach an apocalyptic scenario for human health, not the one that we discussed in the first parts of this review.

Final coda

Massive antibiotic industrial production, its use in humans, animals, and agriculture, and the resulting environmental pollution certainly influences the emergence and spread of antibiotic resistance, decreasing the effectiveness of chemotherapy, and constitutes a problem in public health that should be addressed by applying evolutionary principles (Andersson et al. 2020). However, it is highly improbable that antibiotic resistance could produce an apocalyptic landscape because of failing to control infections (Servitie 2019). In this review we suggest that other effects of antibiotics on the microbiotas and environmental microbiosphere can produce at long-term higher risks, deserving public awareness, by creating social norms to expand the protection of the individual health to the protection of one health and global health (Roca et al. 2015; Berendonk et al. 2015; Hernando-Amado et al. 2020). The threat of the spread of antibiotic-resistant organisms adverts us, once more, that the health of humans and the health of Earth are closely intertwined.