The substantial loss of microbial diversity and specific

The short-term
administration of antibiotics transiently alters the composition of the
intestinal microbiota, but the disturbed intestinal microbiota is normally
normalized after the cessation of antibiotics. 79, 80 The temporary use of antibiotics does not lead
immediate health problems related to diarrhea, allergy and asthma. 81 Controversially, the long-term treatment of AB is well known for disrupting the ecological balance in the
bacterial community, 82 potentially leading to the selection of resistant opportunistic
pathogens which cause acute or chronic disease. 83, 84 Jernberg, C. et al. showed that the long-term compositional
alteration in the microbiota persisted for more than 1 year after AB therapy. 85 This study showed that AB resulted in a substantial loss
of microbial diversity and specific taxa, while the resistant opportunistic
pathogens and resistance genes were increased.86 Even though AB treatment has been reported to protect our
body from pathogenic infections, a rapid perturbation of intestinal microbial
ecosystem by AB in early-life affects the development of inflammatory disorders
87 and acceleration of metabolic diseases.88 Recently, development of multi-omics analysis such as
transcriptomics, proteomics and metabolomics for microbial community profiling
demonstrated that AB affects the microbial community structure and function
such as gene expression, functional activity and overall metabolism. 89, 90 Several studies showed a loss of resilience in the gut microbiota
after administrating a short-course of AB. 86, 91 Clindamycin treatment caused long-term
alteration in the microbial community, resulting in a subsequent susceptibility
to C. difficile infection. 92 Ampicillin treatment decreased microbial diversity in the
intestine and greatly increased Enterobacter
spp. 93 Ciprofloxacin treatment resulted in a reduction in enterobacteria, bacterial diversity and
SCFA production but increased gene expression for vitamin biosynthesis. 79, 94 Vancomycin treatment had a long-lasting
detrimental impact on the intestinal microbial ecology and susceptibility to
any secondary infections. 95, 96 Especially, treatment of AB in early-life has a major
impact on health during entire life. Treatment of AB in infants reduced the
diversity of microbiota and Bifidobacterium.97 Therefore, AB treatment may induce compositional and
functional disturbances, potentially promoting development of various diseases.

Several studies reported that therapeutic
effects of AB interventions reduce the disease-driving bacterial antigens and
the immunosuppressive effects in the course of IBD. 98, 99 Especially, microbial-targeted treatments such as antibiotics
therapy, fecal microbial transplant and probiotics are effective in IBD
patients. 100 This study show that the majority of antibiotics were
found to be implicated in the pathogenesis of IBD through the elimination of
pathogen and reduction of pathogenic immune response. A meta-analysis showed
that antibiotics therapy resulted in the remission of active CD and the
prevention of CD recurrence compared to placebo group. 101 Another trial has been reported that the mixture of
metronidazole and azathioprine resulted in prevention of CD recurrence after
operation. 102 Compared to the CD patients treated with AB, AB therapy
in UC patients is much less effective. The limited evidence reported that the
treatment of sulfasalazine in patients with mild- moderate UC was more
effective than the metronidazole treatment.103 On the other hand, compared to the sulfasalazine, the
metronidazole may prevent the recurrence of UC. 104

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On the contrary, negative effects of AB in
the context of IBD have been reported.105 Except for the effective prevention of pouchitis after
ileal pouch anal anastomosis, there are conflicting data on the therapeutic
relevance of these AB treatments in CD and UC patients.100, 106 A frequent side effect of AB treatment was an increase
in antibiotic resistance such as ciprofloxacin, vancomycin and rifaximin
resistance in IBD patients. 78, 107, 108 Especially, after frequent metronidazole treatment, adverse
effects on gastrointestinal and peripheral neuropathy have been reported. 109 Recently, several studies showed that IBD patients with AB
treatment were associated with an increase in risk for C.dificille infection and recurrence of IBD. 110, 111 Another adverse effect has been reported that exposure
to AB in childhood was strongly associated with the risk of developing IBD. 112 A population based cohort study showed that the AB
therapy in early-life increased the ratio of pathogenesis of CD in adults. 113 A recent study showed that the treatment age, repetition
time and specific class of AB were associated with
early-onset of IBD. 114 For instance, AB exposure in the first year of life
significantly increased pediatric IBD diagnosed at the age of 8 years. 14 A case study revealed that use of metronidazole rather
than other antibiotics was strongly connected with the development of IBD. 115 In addition, metronidazole or fluoroquinolones treatment
was highly relevant to observations in a new-onset of CD. 116

In these contexts, the use of AB might be rather detrimental than
protective in IBD patients in the long term. However, the pathophysiological
mechanisms of development/recurrence of the intestinal inflammation upon
discontinuation of the AB treatment have not yet been investigated.


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