Sexual Dimorphism in the Response to Broad-spectrum Antibiotics During T Cell-mediated Colitis

Harrison, Christy A.; Laubitz, Daniel; Midura-Kiela, Monica T.; Jamwal, Deepa R.; Besselsen, David G.; Kiela, Pawel R.

doi:10.1093/ecco-jcc/jjy144

Cited by 12 publications

(14 citation statements)

References 65 publications

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“…Supplemented water was provided ad libitum and checked daily. Previously, we have described a sexual dimorphism in response to this antibiotic treatment [ 24 ]. Therefore, for this study, we chose only female mice to avoid confounding by sex.…”

Section: Methodsmentioning

confidence: 99%

Dynamics of Gut Microbiota Recovery after Antibiotic Exposure in Young and Old Mice (A Pilot Study)

et al. 2021

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Antibiotics have improved survival from previously deadly infectious diseases. Antibiotics alter the microbial composition of the gut microbiota, and these changes are associated with diminished innate immunity and decline in cognitive function in older adults. The composition of the human microbiota changes with age over the human lifespan. In this pilot study, we sought to identify if age is associated with differential recovery of the microbiota after antibiotic exposure. Using 16S rRNA gene sequencing, we compared recovery of the gut microbiota after the 10-day broad-spectrum antibiotic treatment in wild-type C57BL/six young and older mice. Immediately after antibiotic cessation, as expected, the number of ASVs, representing taxonomic richness, in both young and older mice significantly declined from the baseline. Mice were followed up to 6 months after cessation of the single 10-day antibiotic regimen. The Bray-Curtis index recovered within 20 days after antibiotic cessation in young mice, whereas in older mice the microbiota did not fully recover during the 6-months of follow-up. Bifidobacterium, Dubosiella, Lachnospiraceae_NK4A136_group became dominant in older mice, whereas in young mice, the bacteria were more evenly distributed, with only one dominant genus of Anaeroplasma. From 45 genera that became extinct after antibiotic treatment in young mice, 31 (68.9%) did not recover by the end of the study. In older mice, from 36 extinct genera, 27 (75%) did not recover. The majority of the genera that became extinct and never recovered belonged to Firmicutes phylum and Clostridiales family. In our study, age was a factor associated with the long-term recovery of the gut microbiota after the 10-day antibiotic treatment.

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Section: Methodsmentioning

confidence: 99%

Dynamics of Gut Microbiota Recovery after Antibiotic Exposure in Young and Old Mice (A Pilot Study)

et al. 2021

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“…In the acute DSS mouse colitis model, metronidazole treatment could prevent colonic in ammation, but has no therapeutic effect on established colitis [37]. Metronidazole in combination with cipro oxacin treatment resulted in expansion of Enterococcaceae and Lactobacillaceae in mice [33]. In our study, we found Enterobacteriaceae was also abundant after metronidazole treatment, and a bacterial strain E. ludwigii was identi ed to promote immune tolerance through increasing CD103 + DCs' ability to drive Treg differentiation independent of other intestinal ora.…”

Section: Discussionmentioning

confidence: 63%

“…Metronidazole, as a nitroimidazole preventing nucleic acid synthesis, limits anaerobic bacteria, protozoans and microaerophiles [33]. Metronidazole is medicative in active Crohn's colitis patients and preventive of post operative recurrence of CD in combination with other antibiotics, but has less bene t for ulcerative colitis [34].…”

Section: Discussionmentioning

confidence: 99%

Enterobacter Ludwigii Protects Experimental Colitis Through CD103+DC and Treg Cells

Li¹,

Sun²,

Kobayashi³

et al. 2020

Preprint

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Background: Intestinal bacteria are closely related with inflammatory bowel disease (IBD), and regulatory cell-mediated immune tolerance is important to inhibit IBD. Commensal intestinal bacteria play key roles in regulating immune tolerance cell, however, bacterial strains directly involved in this regulation remain to be identified.Results: In the present study, metronidazole, among nine antibiotics, was found to have the best effect on protecting mice against DSS-induced colitis. Enterobacter ludwigi, abundant in mouse feces after metronidazole treatment, was identified to decrease mice susceptibility to DSS-induced colitis with or without the presence of complex intestinal bacteria. E. ludwigii gavage increased CD103+DCs and Foxp3+Treg cells in intestinal microenvironment, and effects of E. ludwigii on diminishing colitis were lost in DC or Treg depletion mice. CD103+DCs isolated from E. ludwigii-treated mice showed enhanced ability to promote the Treg differentiation from naive T cells. DCs, directly stimulated by live E. ludwigii strain or its culture supernatant, had increased immune tolerance ability for Treg differentiation in vitro. Conclusions: Overall, our findings identify a facultative anaerobe bacterial strain E. ludwigii, which directly enhances CD103+DC and Treg-mediated immune tolerance, resulting in protecting mice against DSS-induced colitis.

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“…Although GMB diversity in the mouse is relatively closer to that of man [ 68 , 69 ] we accepted both mouse and rat studies. We also accepted studies using any combinations of male or female animals, sexual dimorphism notwithstanding [ 44 , 53 , 70 ]. We did not consider metabolome data derived from matrices other than serum, given that changes across these compartments (eg, urine, feces) often correlate poorly [ 44 , 45 , 71 ].…”

Section: Discussionmentioning

confidence: 99%

Changes in the Serum Metabolome of Patients Treated With Broad-Spectrum Antibiotics

Jaskiw

Obrenovich

Kundrapu

et al. 2020

PAI

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Background: The gut microbiome (GMB) generates numerous small chemicals that can be absorbed by the host and variously biotransformed, incorporated, or excreted. The resulting metabolome can provide information about the state of the GMB, of the host, and of their relationship. Exploiting this information in the service of biomarker development is contingent on knowing the GMB-sensitivity of the individual chemicals comprising the metabolome. In this regard, human studies have lagged far behind animal studies. Accordingly, we tested the hypothesis that serum levels of chemicals unequivocally demonstrated to be GMB-sensitive in rodent models would also be affected in a clinical patient sample treated with broad spectrum antibiotics.Methods: We collected serum samples from 20 hospitalized patients before, during, and after treatment with broad-spectrum antibiotics. We also collected samples from 5 control patients admitted to the hospital but not prescribed antibiotics. We submitted the samples for a non-targeted metabolomic analysis and then focused on chemicals known to be affected both by germ-free status and by antibiotic treatment in the mouse and/or rat.Results: Putative identification was obtained for 499 chemicals in human serum. An aggregate analysis did not show any time x treatment interactions. However, our literature search identified 10 serum chemicals affected both by germ-free status and antibiotic treatment in the mouse or rat. Six of those chemicals were measured in our patient samples and additionally met criteria for inclusion in a focused analysis. Serum levels of 5 chemicals (p-cresol sulfate, phenol sulfate, hippurate, indole propionate, and indoxyl sulfate) declined significantly in our group of antibiotic-treated patients but did not change in our patient control group.Conclusions: Broad-spectrum antibiotic treatment in patients lowered serum levels of selected chemicals previously demonstrated to be GMB-sensitive in rodent models. Interestingly, all those chemicals are known to be uremic solutes that can be derived from aromatic amino acids (L-phenylalanine, L-tyrosine, or L-tryptophan) by anaerobic bacteria, particularly Clostridial species. We conclude that judiciously selected serum chemicals can reliably detect antibiotic-induced suppression of the GMB in man and thus facilitate further metabolome-based biomarker development.

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Sexual Dimorphism in the Response to Broad-spectrum Antibiotics During T Cell-mediated Colitis

Abstract: While preliminary, our results suggest a differential response to both inflammation and Abx between male and female mice, The findings may be relevant to current practice and as the basis for further studies on the differential gender effects during long term antibiotic exposure in IBD.

Cited by 12 publications

References 65 publications

Dynamics of Gut Microbiota Recovery after Antibiotic Exposure in Young and Old Mice (A Pilot Study)

Dynamics of Gut Microbiota Recovery after Antibiotic Exposure in Young and Old Mice (A Pilot Study)

Enterobacter Ludwigii Protects Experimental Colitis Through CD103+DC and Treg Cells

Changes in the Serum Metabolome of Patients Treated With Broad-Spectrum Antibiotics

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