Antibiotics and the Microbiome
Antibiotic overuse, rates, harms, resistance. Restoring & preventing the damage to the gut microbiome and immune system.
Commentary:
Antibiotic resistance gets all the attention, while collateral damage has been continually ignored despite all the warnings, evidence, and arguably more severe consequences.
FMT looks like an easy solution for resistance, but based on the evidence throughout this wiki, and my own experiences of FMTs from 12+ different donors, the collateral damage is extremely difficult to reverse and may not be possible with only FMT, especially due to how rare non-damaged stool donors are.
Antibiotic-overuse rates are very high as is. And given that none of the current guidelines take into account the collateral damage to the immune system and gut microbiome, antibiotic-overuse-rates are likely much higher than current estimates.
Ecologists are well aware that you can't simply kill off all mosquitoes due to the threat of malaria, because many other wildlife in the ecosystem are dependent on mosquitoes. Yet with antibiotics, this is exactly what we've been doing over and over and over for generations. Continually killing off more and more of our host-native microbiomes that have been evolving alongside us for millions of years. And unlike with a targeted-kill approach on only-mosquitoes, antibiotics are not that targeted, and thus do extensive collateral damage well beyond their target.
There are more sections in other parts of the wiki. Eg: https://humanmicrobiome.info/cancer/#antibiotics
General
CDC | Will antibiotics help for these common infections? https://web.archive.org/web/20230331041840/https://www.cdc.gov/antibiotic-use/common-illnesses.html
An analytical, cost-benefit approach to antibiotics.
IV vs oral, which is more harmful: https://archive.is/9QV89
Responses are individualized [1][2][3]. 2020 study finds 21 bacterial species associated with ecological recovery post antibiotic therapy.
Some evidence suggests you shouldn't give antibiotics while the target is nutrient starved [1][2][3].
Natural antimicrobials like Oil of Oregano and Iodine are broad-spectrum, and thus not safer than prescription abx. https://forum.humanmicrobiome.info/threads/high-dose-iodine-and-oil-of-oregano-are-broad-spectrum-antimicrobials.33/
Non-Antibiotic Approaches to Infection that Preserve the Microbiome in Critically Ill Patients (2023) https://www.liebertpub.com/doi/10.1089/sur.2023.020
More via the "antibiotics" forum category: https://forum.humanmicrobiome.info/forums/microbiome-studies-articles/?prefix_id=2
Antibiotics Course:
Why your doctor’s advice to take all your antibiotics may be wrong: https://forum.humanmicrobiome.info/threads/completing-antibiotic-courses-is-a-medical-advice-myth-that-may-make-b.138/
Appropriate Use of Short-Course Antibiotics in Common Infections: Best Practice Advice From the American College of Physicians (Apr 2021) https://www.acpjournals.org/doi/10.7326/M20-7355
Shorter (7 day vs 14 day), tailored antibiotic regimens shown effective at treating bacterial infections. 14 day regimens seem to be based on medical tradition rather than on sound scientific evidence (Jun 2020, n=504 adults) https://medicalxpress.com/news/2020-06-shorter-tailored-antibiotic-regimens-shown.html
Is it time to stop counselling patients to “finish the course of antibiotics”? (2017) https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5661683/
"With a few notable exceptions, most of the time I am making up the duration of an antibiotic course" -MD, Infectious Disease https://archive.ph/ldTT2#selection-9335.10-9335.11
Rates of antibiotics use:
20–25% of women are prescribed antibiotics during pregnancy (2015): http://onlinelibrary.wiley.com/doi/10.1002/phar.1649/abstract
"In the USA, about one in two women is prescribed an antibiotic during pregnancy or at term" (2019): https://gut.bmj.com/content/early/2019/01/22/gutjnl-2018-317503.long
69 Percent of Kids in the US Exposed to Antibiotics Before Age 2 (2014): https://www.healthline.com/health-news/childhood-antibiotics-exposure-raises-obesity-risk-092914#1 - https://jamanetwork.com/journals/jamapediatrics/fullarticle/1909801
Children receive a mean of 2.7 antibiotic courses by age 2, and 10.9 by age 10 (2018): https://web.archive.org/web/20190423131149/https://www.mdedge.com/ccjm/article/189671/infectious-diseases/our-missing-microbes-short-term-antibiotic-courses-have-long/page/0/1
Australian babies given antibiotics at some of the highest rates in the world (2017): https://www.theguardian.com/society/2017/jul/28/australian-babies-given-antibiotics-at-some-of-the-highest-rates-in-the-world - https://doi.org/10.1111/jpc.13616
Antibiotic Use in Children – A Cross-National Analysis of 6 Countries (Dec 2016) https://www.jpeds.com/article/S0022-3476(16)31256-2/fulltext "We found substantial differences of up to 7.5-fold in pediatric antimicrobial use across several industrialized countries from Europe, Asia, and North America. These data reinforce the need to develop strategies to decrease the unnecessary use of antimicrobial agents"
Antibiotics Overuse:
An estimated 80-90% of the volume of human antibiotic use occurs in the outpatient setting. At least 28% of antibiotics prescribed in the outpatient setting are unnecessary, meaning that no antibiotic was needed at all. Total inappropriate antibiotic use [..] may approach 50% of all outpatient antibiotic use. https://web.archive.org/web/20230919074923/https://www.cdc.gov/antibiotic-use/data/outpatient-prescribing/index.html
“Antibiotics are among the most commonly prescribed medications for children, but prior research has suggested that nearly a third, if not more, of outpatient pediatric prescriptions for antibiotics are unnecessary”. Adults too [2016][Jan 2019][Mar 2019][Dec 2019].
Systematic Review of Factors Associated with Antibiotic Prescribing for Respiratory Tract Infections (2016) https://journals.asm.org/doi/10.1128/AAC.00209-16 "the majority of RTIs are viral and therefore do not improve with use of an antibiotic. A substantial proportion of antibiotic use for RTIs is, therefore, inappropriate. Physician's perception of patient desire for antibiotics was strongly associated with antibiotic prescribing"
Antibiotics for acute respiratory infections in general practice: comparison of prescribing rates with guideline recommendations (2017): https://www.mja.com.au/journal/2017/207/2/antibiotics-acute-respiratory-infections-general-practice-comparison-prescribing "Antibiotics are prescribed for ARIs at rates,–9 times as high as those recommended by Therapeutic Guidelines"
Fifty-two percent of CF infants prescribed antibiotics for symptoms (respiratory) had a virus. (Feb 2019): https://www.cysticfibrosisjournal.com/article/S1569-1993(18)30804-X/fulltext
In a Poor Kenyan Community, Cheap Antibiotics Fuel Deadly Drug-Resistant Infections. Overuse of the medicines is not just a problem in rich countries. Throughout the developing world antibiotics are dispensed with no prescription required. One study found that 90 percent of households in the neighborhood had used antibiotics in the previous year. (April 2019): https://www.nytimes.com/2019/04/07/health/antibiotic-resistance-kenya-drugs.html
Antibiotics and the developing intestinal microbiome, metabolome and inflammatory environment in a randomized trial of preterm infants (Jan 2021, n=98) https://www.nature.com/articles/s41598-021-80982-6 "A majority of preterm neonates receive antibiotics after birth without clear evidence to guide this practice"
Large study finds antibiotics aren't effective for most lower tract respiratory infections (Apr 2024, n=718) Antibiotics Not Associated with Shorter Duration or Reduced Severity of Acute Lower Respiratory Tract Infection https://forum.humanmicrobiome.info/threads/large-study-finds-antibiotics-arent-effective-for-most-lower-tract-res.350/
Antibiotics for GBS (Group-B Strep):
Current evidence does not support antibiotics for GBS:
Group B streptococcal screening, intrapartum antibiotic prophylaxis, and neonatal early-onset infection rates in an Australian local health district: 2006-2016 (April 2019): https://journals.plos.org/plosone/article?id=10.1371/journal.pone.0214295 "Seven of 10 term babies with EOGBS were born to mothers who screened negative. No change was detected in rates of neonatal early-onset group B streptococcal infection (EOGBS) over time and no difference in EOGBS in babies of screened and unscreened populations. Limitations of universal screening suggest alternatives be considered."
Intrapartum antibiotics for known maternal Group B streptococcal colonization (2014): https://www.cochrane.org/CD007467/PREG_intrapartum-antibiotics-known-maternal-group-b-streptococcal-colonization "giving antibiotics is not supported by conclusive evidence, no clear differences in newborn deaths"
The 2019 US guidelines ignored those systematic reviews & new evidence, and downplayed the harms of antibiotics: https://forum.humanmicrobiome.info/threads/just-3-people-are-responsible-for-30-of-infants-and-mothers-in-the-us.46/
2017 article: https://evidencebasedbirth.com/groupbstrep/
Dr Martin Blaser and others have criticized the extreme and harmful approach of "To prevent infection in one infant, we are exposing 200 infants to the unwanted effects of antibiotics. A more balanced, more nuanced approach is possible."
An analytical, cost-benefit approach to antibiotics for GBS.
Antibiotics for Dentistry:
Antibiotics for dental work; no evidence they help, yet dentists are randomly giving them out: https://www.washingtonpost.com/national/health-science/did-his-artificial-hips-put-him-at-risk-of-infection-when-he-saw-the-dentist/2016/10/07/1a0d4b54-60a5-11e6-9d2f-b1a3564181a1_story.html
Most preventive antibiotics prescribed by dentists are unnecessary (2019) https://today.uic.edu/most-preventive-antibiotics-prescribed-by-dentists-are-unnecessary
Antibiotics for Ear Infections:
Middle ear infection: Will antibiotics help relieve symptoms in babies and toddlers? (2019) https://www.ncbi.nlm.nih.gov/books/NBK279379/ - often ineffective.
Middle ear infections (otitis media) will usually clear up within a few days, with or without treatment. (2019) https://www.ncbi.nlm.nih.gov/books/NBK279379/
CDC guidance for ear infections https://www.cdc.gov/ear-infection/about/
Cochrane: Antibiotics for acute middle ear infection (acute otitis media) in children (2015): https://www.cochrane.org/CD000219/ARI_antibiotics-for-acute-middle-ear-infection-acute-otitis-media-in-children
American Academy of Pediatrics| Clinical Practice Guideline| March 01 2013 | The Diagnosis and Management of Acute Otitis Media https://publications.aap.org/pediatrics/article/131/3/e964/30912/The-Diagnosis-and-Management-of-Acute-Otitis-Media "Deafness from ear infections would be uncommon. The vast majority of children feel better within 24-72 hours with very, very rare complications. The American academy of pediatrics has acknowledged this body of research and updated their guidelines in 2013. The majority of ear infections do not need antibiotics, and the positive effect of antibiotics on ear infections is actually quite modest, as antibiotics have difficulty reaching the middle ear."
Hydrogen peroxide in the ear seems fairly effective unless it's a major infection:
- https://jamanetwork.com/journals/jamaotolaryngology/article-abstract/589948
- https://onlinelibrary.wiley.com/doi/abs/10.1288/00005537-194909000-00007
Antibiotics for Surgery:
Prophylactic antibiotics and caesarean section. (1990) https://www.bmj.com/content/300/6716/2 - says antibiotics aren't always necessary during c-sections. Yet many countries give them out 100% of the time. The article ignores collateral damage done to the human microbiome, but that's not surprising considering it was written in 1990. But I couldn't find one written in the past 10 years.
Antibiotic prophylaxis (2001) https://www.ncbi.nlm.nih.gov/books/NBK6917/ "Controversy exists about the necessity of antibiotic prophylaxis in clean operations. The argument against the prophylaxis is the low wound infection rate of 2% and less. However, it is well recognized that 40% of wound infections occur after clean operations"
WHO 2018 guidelines (risk-assessement-based use): https://www.who.int/infection-prevention/publications/ssi-prevention-guidelines/en/ - "A systematic review of 57 studies from both high-income countries and LMICs identified the following factors associated with an increased risk of SSI (surgery site infection) in adjusted analysis: a high body mass index; a severe score according to the US National Nosocomial Infections Surveillance (NNIS) risk index; severe wound class; diabetes; and a prolongation of surgery duration"
Swedish 2010 article mentioning prophylactic antibiotics aren't always given during surgeries, including c-sections, but seems to be advocating for more use of them: https://www.sbu.se/sv/publikationer/vetenskap-och-praxis/antibiotika-ratt-profylax-fore-operation-kan-minska-resistens-och-infektioner/ - only recognized harm of antibiotics is resistance. "Today there are too few studies to safely conclude if antibiotic prophylaxis is cost effective, even if some result point in that direction".
The cited PDF: Swedish Council on Health Technology Assessment https://translate.google.com/translate?sl=auto&tl=en&js=y&u=https%3A%2F%2Fwww.sbu.se%2Fcontentassets%2Fea33b7102afb40b2ad43fe3d9566b386%2Fantibiotikaprofylax_sammanfattning.pdf says "The scientific evidence is insufficient to assess the effect of antibiotic prophylaxis in several surgical procedures where it is used today. The lack of empirical studies means that there is no evidence for efficacy of antibiotic prophylaxis."
Contribution of the patient microbiome to surgical site infection and antibiotic prophylaxis failure in spine surgery (Apr 2024, n=204) https://forum.humanmicrobiome.info/threads/infections-after-surgery-are-more-likely-due-to-bacteria-already-on-yo.344/ "for most individuals, the bacteria responsible for the surgical site infection, along with any antibiotic resistance genes circumventing the chosen prophylactic antibiotic, were likely already present on the patient’s own skin before the first incision. These findings suggest a need for alternative antiseptic strategies. Most SSI isolates (59%) were resistant to the prophylactic antibiotic administered during surgery"
Antibiotics are the main cause of life threatening allergic reactions during surgery (2018): https://www.bmj.com/content/361/bmj.k2124
Harms of antibiotics:
More studies showing long-term harms here: https://humanmicrobiome.info/maternity and via the "antibiotics" forum category: https://forum.humanmicrobiome.info/forums/microbiome-studies-articles/?prefix_id=2.
Even FMT may not be able to reverse the damage done: https://link.springer.com/article/10.1007/s00248-020-01525-6 "we found that control mice did not restore disturbed microbial communities. Instead, mice with disturbed microbial communities induced disturbance in control mice"
While antibiotic resistance gets all the attention, the damage being done to our host-native microbiomes that have evolved alongside us for millions of years is arguably as big a threat as climate change, as the damage compounds over generations, and once it's gone you can't get it back. https://forum.humanmicrobiome.info/threads/while-antibiotic-resistance-gets-all-the-attention-the-damage-being-do.50/ - includes the paper "Preserving microbial diversity (Oct 2018)".
Review, 2023: Antibiotic-induced collateral damage to the microbiota and associated infections https://www.nature.com/articles/s41579-023-00936-9
Review, 2022: Impact of antibiotics on the human microbiome and consequences for host health https://onlinelibrary.wiley.com/doi/10.1002/mbo3.1260 "we discuss the adverse effects of antibiotics on the gut microbiota and thus host health, and suggest alternative approaches to antibiotic use"
Review, 2018: Fire in the Forest: Adverse Effects of Antibiotics on the Healthy Human Gut Microbiome http://www.ijmedrev.com/article_76662.html "Short-term antibiotic treatment is able to change the richness and diversity of species into a long-term dysbiotic state"
Review, 2018: Antibiotics and the nervous system: More than just the microbes? https://doi.org/10.1016/j.bbi.2018.12.014 "clinical as well as experimental literature, largely neglected through the past decade, has clearly demonstrated that broad classes of antibiotics are neuroactive or neurotoxic. This is true even for some antibiotics that are widely regarded as not absorbed in the intestinal tract"
Review, 2018: Antibiotics and autoimmune and allergy diseases: Causative factor or treatment? https://www.sciencedirect.com/science/article/pii/S1567576918304752 "Antibiotics use in children promotes the development of allergic disorders, whereas antibiotics use in adults seems to ameliorate inflammatory responses and reduce the severity of autoimmune diseases"
Review, 2017: Antibiotic use and microbiome function: http://www.sciencedirect.com/science/article/pii/S0006295216302866
Review, 2017: Association between prior antibiotic therapy and subsequent risk of community-acquired infections: a systematic review: https://academic.oup.com/jac/advance-article-abstract/doi/10.1093/jac/dkx374/4629206 "Our findings support the hypothesis that antibiotic use may predispose to future infection risk"
Some of the changes caused by antibiotics are transient and can be reversed at the end of the treatment, while others seem irreversible. Most importantly, it has been observed that gut bacteria present a lower capacity to produce proteins, as well as display deficiencies in key activities, during and after the antibiotic treatment. For instance, antibiotics decrease the ability to absorb iron, to digest certain foods and to produce essential molecules. Previously it was assumed that short-term antibiotic treatment would alter gut microbe composition only for a short time, however, this is not the case. Even a relatively short course of antibiotics can lead to alteration in gut microbiota, which in turn can lead to severe consequences such as inflammation, immune dysregulation, allergies, infections, cardiovascular diseases, diabetes, metabolic issues, GI disease such as Crohn’s, IBD, yeast overgrowth, chronic constipation and diarrhea (2018) https://www.frontiersin.org/articles/10.3389/fncel.2018.00256/full#h4
The long-term consequences of antibiotic therapy: Role of colonic short-chain fatty acids (SCFA) system and intestinal barrier integrity (Aug 2019, rats, ceftriaxone) https://journals.plos.org/plosone/article?id=10.1371/journal.pone.0220642 "first report on the role of the SCFA system in the long lasting side effects of antibiotic treatment and its implication in IBD development"
According to a modelling study by UCL researchers, a single course of antibiotics can change the composition of oral and gut microbiomes for at least a year, perhaps permanently. https://www.ucl.ac.uk/news/2019/mar/how-antibiotics-change-human-microbiome-diversity-long-term - Modelling microbiome recovery after antibiotics using a stability landscape framework (Mar 2019) https://www.nature.com/articles/s41396-019-0392-1
"Whereas microbial diversity recovered rapidly in lemurs, antibiotics caused long-term instability in community composition" (Nov 2020) https://www.biorxiv.org/content/10.1101/2020.11.11.378349v1
"in other cases, the strains present after antibiotics were genetically different from those at the start even though the abundance of the species did not change" (2021) https://www.eurekalert.org/news-releases/938898
Antibiotics create a shift from mutualism to competition in human gut communities with a longer-lasting impact on fungi than bacteria (Sep 2020, n=12) https://microbiomejournal.biomedcentral.com/articles/10.1186/s40168-020-00899-6
Antibiotic Scars Left on the Gut Microbiota from the Stringent Response (2018): https://www.cell.com/trends/microbiology/fulltext/S0966-842X(18)30138-0 - "Current research is primarily focused on compositional shifts and alterations in the metabolic status of the gut microbiota to elucidate the damage caused by antibiotics. However, the impact of the stringent response, which is governed by a global gene regulatory system conserved in most gut bacteria, should not be overlooked."
"Alterations to microbial metabolic capacity occurred following antimicrobial exposure even in participants without substantial taxonomic disruption. Our findings suggest that metabolic potential is an important consideration for complete assessment of antimicrobial impact on the microbiome" (2018): https://msphere.asm.org/content/3/6/e00588-18
"We find that antibiotics can drive rapid shifts in the genetic composition of individual species. Interestingly, genetic changes frequently occur in species without obvious changes in relative species abundance, emphasizing the importance of monitoring diversity below the species level" (2019) https://www.biorxiv.org/content/10.1101/2019.12.21.886093v1
Pre-transplant recovery of microbiome diversity without recovery of the original microbiome (2018): https://sci-hub.se/https://www.nature.com/articles/s41409-018-0414-z "our findings suggest that recovery of diversity alone is not an adequate surrogate for microbiome recovery. Microbiota composition and its potential functionality should be considered along with diversity in drawing conclusions from microbiome studies"
Clinically used broad-spectrum antibiotics compromise inflammatory monocyte-dependent antibacterial defense in the lung (Mar 2024) https://www.nature.com/articles/s41467-024-47149-z
Long-term impact of oral vancomycin, ciprofloxacin and metronidazole on the gut microbiota in healthy humans (Nov 2018) https://academic.oup.com/jac/advance-article-abstract/doi/10.1093/jac/dky471/5173727 "combined treatment with broad-spectrum antibiotics has a profound & long-lasting effect on microbiota composition, the consequences of which remain largely unknown"
"expansion of a certain species of house dust fungus (Wallemia mellicola) can occur in the intestines of mice after they are treated with antibiotics and exposed to the fungus. By contrast, mice with an intact and healthy intestinal microbiota resist this expansion. After expansion of this fungal population, the mice are more prone to develop asthma-like inflammation in their lungs when exposed to allergens" https://www.eurekalert.org/pub_releases/2018-09/p-gfe091318.php
"We identified valerate as a metabolite that is depleted with clindamycin and only recovered with FMT." https://www.gastrojournal.org/article/S0016-5085(18)34771-1/fulltext "Inhibiting Growth of Clostridioides difficile by Restoring Valerate, Produced by the Intestinal Microbiota (2018)"
Substantial reduction in microbiota diversity in subjects who took either amoxicillin or azithromycin and that those reductions were sustained throughout the 6-month study (2016): http://microbiomejournal.biomedcentral.com/articles/10.1186/s40168-016-0187-9
Early life antibiotic exposure affects pancreatic islet development and metabolic regulation. Changes in the expression of key genes involved in short-chain fatty acid signaling and pancreatic development were detected in later life (2017): http://www.nature.com/articles/srep41778
Antibiotic-induced gut microbiota disruption promotes vascular calcification by reducing short-chain fatty acid acetate (Aug 2024, mice) https://forum.humanmicrobiome.info/threads/antibiotic-induced-gut-microbiota-disruption-promotes-vascular-calcifi.560/
Low-dose penicillin in early life induces long-term changes in murine gut microbiota, brain cytokines and behavior (2017): https://www.nature.com/articles/ncomms15062
Association of doxycycline use with the development of gastroenteritis, irritable bowel syndrome and inflammatory bowel disease in Australians deployed abroad (2013) https://onlinelibrary.wiley.com/doi/10.1111/imj.12179
Testosterone disruptor effect and gut microbiome perturbation in mice: Early life exposure to doxycycline (Jan 2019): https://www.sciencedirect.com/science/article/pii/S0045653519301110 "Early-life exposure to doxycycline shows negative outcomes of testis health in later-life. Early-life exposure to low-dose of doxycycline associates with increased risk of obesity."
Infant antibiotic use linked to adult diseases (2015): https://www.sciencedaily.com/releases/2015/05/150513140929.htm - Antibiotics, Pediatric Dysbiosis, and Disease http://dx.doi.org/10.1016/j.chom.2015.04.006
Incomplete recovery and individualized responses of the human distal gut microbiota to repeated antibiotic (ciprofloxacin) perturbation (2011): https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3063582/
Antibiotics that kill gut bacteria also stop growth of new brain cells: https://www.sciencedaily.com/releases/2016/05/160519130105.htm
Long-term antibiotic use during early life and risks to mental traits: an observational study and gene–environment-wide interaction study in UK Biobank cohort (Aug 2020, n=158,444) https://www.nature.com/articles/s41386-020-00798-2
Antibiotics impair murine hematopoiesis by depleting intestinal microbiota (2016): https://doi.org/10.1182/blood-2016-03-708594
Bactericidal Antibiotics Induce Mitochondrial Dysfunction and Oxidative Damage in Mammalian Cells (2013): http://dx.doi.org/10.1126/scitranslmed.3006055
Inhibited mitochondrial gene expression and amounts of active mitochondria, increasing epithelial cell death. Kill intestinal epithelium cells (2015): https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5166700/ - https://www.medicalnewstoday.com/articles/289259.php
Linked to Sepsis risk (2016): http://www.medpagetoday.com/meetingcoverage/idweek/61073
Encourage spread of c.diff to people who haven't taken antibiotics (2016): https://web.archive.org/web/20201108140052/https://medicalresearch.com/author-interviews/antibiotics-encourage-spread-c-diff-patients-havent-received-antibiotics/28609/
Reduces gut diversity of housemates who haven’t taken antibiotics: http://microbiomejournal.biomedcentral.com/articles/10.1186/s40168-016-0187-9 Microbial diversity in individuals and their household contacts following typical antibiotic courses (2016).
In antibiotics-treated mice, serotonin, tryptophan hydroxylase 1, and secondary bile acids levels were decreased: https://translational-medicine.biomedcentral.com/articles/10.1186/s12967-016-1105-4 Antibiotics-induced depletion of mice microbiota induces changes in host serotonin biosynthesis and intestinal motility (2017).
Depletion of the gut microbiome by antibiotics impairs the body's ability to eliminate toxins like arsenic and mercury.
Antifungals also do collateral damage: Disruption of Intestinal Fungi Leads to Increased Severity of Inflammatory Disease https://news.weill.cornell.edu/news/2016/06/disruption-of-intestinal-fungi-leads-to-increased-severity-of-inflammatory-disease. Immunological Consequences of Intestinal Fungal Dysbiosis (2016).
Virome:
Negative impact on the phageome; low doses can make phages go extinct by making bacteria resistant to them (2016): https://archive.is/lHdQG. Genomic evolution of bacterial populations under coselection by antibiotics and phage.
Antibiotics alter and deplete the virome (DNA viruses, RNA viruses, phages, 2019): https://virologyj.biomedcentral.com/articles/10.1186/s12985-019-1211-z
Impact of antibiotic perturbation on fecal viral communities in mice (2022) https://academic.oup.com/g3journal/advance-article/doi/10.1093/g3journal/jkac293/6839982 "Viral community composition only partially recovered. Compositional shifts in the virome and bacteriome were highly correlated, suggesting that the loss of specific phages may contribute to prolonged dysregulation of the bacterial community composition"
Damage immune system:
Antibiotic-Induced Changes to the Host Metabolic Environment Inhibit Drug Efficacy and Alter Immune Function (2017): https://www.cell.com/cell-host-microbe/fulltext/S1931-3128(17)30455-9 - https://newatlas.com/antibiotics-counteract-immune-system/52457/
Antibiotics found to weaken the immune system's ability to fight off disease (neutrophils, 2017): https://www.eurekalert.org/pub_releases/2017-08/uovh-aft081717.php
Once the microbiota is destroyed by antibiotics, the immune reaction no longer occurs (Mar 2019): https://www.eurekalert.org/pub_releases/2019-03/ip-doa031919.php. A Weaning Reaction to Microbiota Is Required for Resistance to Immunopathologies in the Adult.
A single early-life macrolide antibiotic course can alter the microbiota and modulate host immune phenotypes that persist long after exposure has ceased (2017): https://www.nature.com/articles/s41467-017-00531-6
This mouse study suggests FMT may not completely restore immune function damaged by antibiotics (2017): https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5395657/ "Immune Responses to Broad-Spectrum Antibiotic Treatment and Fecal Microbiota Transplantation in Mice"
"Although the results cannot prove causality, these findings provide evidence for the involvement of infections and the immune system in the etiology of a wide range of mental disorders in children and adolescents" https://theconversation.com/how-childhood-infections-requiring-antibiotics-may-increase-risks-of-mental-illness-110965 A Nationwide Study in Denmark of the Association Between Treated Infections and the Subsequent Risk of Treated Mental Disorders in Children and Adolescents (Dec 2018).
[Broad-spectrum] Antibiotics induce sustained dysregulation of intestinal T cell immunity by perturbing macrophage homeostasis (Oct 2018, mice) https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6548564/ - FMT was not able to reverse the damage, but butyrate supplementation was able to prevent it.
Damage gut barrier/mucosa:
A history of repeated antibiotic usage leads to microbiota-dependent mucus defects (Jul 2024) https://forum.humanmicrobiome.info/threads/a-history-of-repeated-antibiotic-usage-leads-to-microbiota-dependent-m.501/
Antibiotics damage the colonic mucus barrier in a microbiota-independent manner (Sep 2024, mice) https://forum.humanmicrobiome.info/threads/antibiotics-damage-the-colonic-mucus-barrier-in-a-microbiota-independe.580/ "Antibiotic use is a risk factor for development of inflammatory bowel diseases (IBDs)"
Antibiotic Resistance:
Review, 2020: The Gut Microbiome as a Reservoir for Antimicrobial Resistance https://academic.oup.com/jid/article/223/Supplement_3/S209/6039355?
Review, 2013: The human microbiome as a reservoir of antimicrobial resistance https://www.frontiersin.org/journals/microbiology/articles/10.3389/fmicb.2013.00087/full
Review, 2012: The gut is the epicentre of antibiotic resistance https://aricjournal.biomedcentral.com/articles/10.1186/2047-2994-1-39
The distribution of antibiotic use and its association with antibiotic resistance (2018): https://doi.org/10.7554/eLife.39435.001
Neighborhood Antibiotic Use May Increase Individual Risk for Resistant Bacteria (April 2019): https://www.infectiousdiseaseadvisor.com/home/topics/emerging-diseases/antibiotics-antimicrobial-resistance/neighborhood-antibiotic-use-may-increase-individual-risk-for-resistant-bacteria/. Association between urinary community-acquired fluoroquinolone-resistant Escherichia coli and neighbourhood antibiotic consumption: a population-based case-control study.
Acquisition of multidrug-resistant organisms in the absence of antimicrobial exposure (2018): https://academic.oup.com/cid/advance-article-abstract/doi/10.1093/cid/ciy358/4984601 - Another in 2019.
Non-antibiotic drugs promote antibiotic resistance. These accidental bactericides included proton-pump inhibitors such as omeprazole, calcium-channel blockers, antihistamines, painkillers and antipsychotics. (2018): https://www.theguardian.com/science/2018/mar/19/wide-range-of-drugs-affect-gut-microbes-not-just-antibiotics. Extensive impact of non-antibiotic drugs on human gut bacteria.
Triclosan exposure may inadvertently drive bacteria into a state in which they are able to tolerate normally lethal concentrations of antibiotics (2019): https://www.sciencedaily.com/releases/2019/02/190221172048.htm The widely used antimicrobial triclosan induces high levels of antibiotic tolerance in vitro and reduces antibiotic efficacy up to 100-fold in vivo http://dx.doi.org/10.1128/AAC.02312-18
Human Milk Microbiota: Transferring the Antibiotic Resistome to Infants (Sep 2019) https://link.springer.com/article/10.1007%2Fs12088-019-00824-y
Effects of antibiotic duration on the intestinal microbiota and resistome: The PIRATE RESISTANCE project, a cohort study nested within a randomized trial (Sep 2021, n=56) https://www.thelancet.com/journals/ebiom/article/PIIS2352-3964(21)00359-5/fulltext "Reducing antibiotic durations by half did not result in decreased abundance of ARGs in patients treated for gram-negative bacteraemia, nor did it improve microbiota species diversity"
FMT to counter antibiotic resistance:
Review, Oct 2021: Faecal microbiota replacement to eradicate antimicrobial resistant bacteria in the intestinal tract – a systematic review https://journals.lww.com/co-gastroenterology/Abstract/9000/Faecal_microbiota_replacement_to_eradicate.99000.aspx
Review, Mar 2019: Faecal microbiota transplantation for the decolonisation of antibiotic-resistant bacteria in the gut: a systematic review and meta-analysis https://www.journalofhospitalinfection.com/article/S0195-6701(19)30114-8/abstract "Despite the limitations of the included studies, evidence from this review indicates a potential benefit of FMT as a decolonisation intervention, which can only be confirmed by future well-designed RCTs"
Long-term beneficial effect of faecal microbiota transplantation on colonisation of multidrug-resistant bacteria and resistome abundance in patients with recurrent Clostridioides difficile infection (Feb 2024, n=87) https://genomemedicine.biomedcentral.com/articles/10.1186/s13073-024-01306-7
Fecal microbiota transplantation promotes reduction of antimicrobial resistance by strain replacement (Nov 2023, n=11, RCT) https://www.science.org/doi/10.1126/scitranslmed.abo2750
Faecal microbiota transplantation reduces amounts of antibiotic resistance genes in patients with multidrug-resistant organisms (Jan 2022, n=29) https://aricjournal.biomedcentral.com/articles/10.1186/s13756-022-01064-4
Fecal Microbiota Transplant Mitigates Adverse Outcomes Seen in Patients Colonized With Multidrug-Resistant Organisms Undergoing Allogeneic Hematopoietic Cell Transplantation (Aug 2021, n=19) https://www.frontiersin.org/articles/10.3389/fcimb.2021.684659/full
Fecal transplant in children with Clostridioides difficile gives sustained reduction in antimicrobial resistance and potential pathogen burden (Aug 2019) https://academic.oup.com/ofid/advance-article/doi/10.1093/ofid/ofz379/5554472 "FMT for CDI in children decreases AMR genes and potential pathogens and changes microbiota composition and function. However, acquisition of certain AMR genes post-FMT combined with low levels of potential pathogens found in donors suggests further study is warranted regarding screening donors using metagenomics sequencing prior to FMT"
The role of fecal microbiota transplantation to reduce intestinal colonization with antibiotic-resistant organisms: the current landscape and future directions (June 2019) https://doi.org/10.1093/ofid/ofz288
Fifty shades of graft: how to improve efficacy of Fecal Microbiota Transplantation (FMT) for decolonization of Antibiotic-Resistant Bacteria (ARB)? (Mar 2019): https://www.sciencedirect.com/science/article/pii/S0924857919300615
Faecal microbiota transplant for eradication of multidrug-resistant Enterobacteriaceae: a lesson in applying best practice? (2019): https://sci-hub.tw/https://doi.org/10.1016/j.cmi.2019.01.010
Impact of Amoxicillin/Clavulanate and Autologous Fecal Microbiota Transplantation (FMT) on the Fecal Microbiome and Resistome (2016): https://academic.oup.com/ofid/article/3/suppl_1/2228/2636541
Fecal Microbial Transplantation for the Treatment of Persistent Multidrug-Resistant Klebsiella pneumoniae Infection in a Critically Ill Patient (Feb 2020) https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7038171
"Combined antibiotic and FMT treatment resulted in enrichment of species that are likely to limit the gut colonization by ESBL-E/CPE" (Jun 2020, clinical trial, n=26) https://www.mdpi.com/2076-2607/8/6/941 Metagenomic Characterization of Gut Microbiota of Carriers of Extended-Spectrum Beta-Lactamase or Carbapenemase-Producing Enterobacteriaceae Following Treatment with Oral Antibiotics and Fecal Microbiota Transplantation: Results from a Multicenter Randomized Trial.
Disease prevention not decolonization – a model for fecal microbiota transplantation in patients colonized with multidrug-resistant organisms (Jul 2020, n=20) https://academic.oup.com/cid/article/doi/10.1093/cid/ciaa948/5873448
Fecal Microbiota Transplantation for multidrug-resistant organism: Efficacy and Response prediction (Sep 2020, n=35) https://www.journalofinfection.com/article/S0163-4453(20)30597-1/fulltext
Tandem fecal microbiota transplantation cycles in an allogeneic hematopoietic stem cell transplant recipient targeting carbapenem-resistant Enterobacteriaceae colonization: a case report and literature review (Apr 2021) https://eurjmedres.biomedcentral.com/articles/10.1186/s40001-021-00508-8
Misc:
In a lab, researchers created three new antibiotics that kill C. difficile by preventing the expression of bacterial genes that are important for its survival. This approach — called antisense therapy — allows the drug to kill only C. difficile, unlike many antibiotics that kill multiple forms of bacteria. (2018): http://news.psu.edu/story/523890/2018/06/06/research/killing-bacteria-silencing-genes-may-be-alternative-antibiotics
Unravelling the collateral damage of antibiotics on gut bacteria (Oct 2021) https://www.nature.com/articles/s41586-021-03986-2 "These findings illluminate the activity spectra of antibiotics in commensal bacteria and suggest strategies to circumvent their adverse effects on the gut microbiota"