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Ly6C(hi) Monocytes Provide a Link between Antibiotic-Induced Changes in Gut Microbiota and Adult Hippocampal

Luisa Möhle1, Daniele Mattei2, Markus M Heimesaat3

  • 1Institute of Medical Microbiology, University of Magdeburg, 39106 Magdeburg, Germany.

Cell Reports
|May 24, 2016
PubMed

Insights

Antibiotic treatment impairs mouse brain neurogenesis and memory. Gut flora restoration, exercise, or probiotics can help, partly by increasing specific immune cells called Ly6C(hi) monocytes.

Area of Science:

  • Neuroscience
  • Immunology
  • Microbiology

Background:

  • Antibiotics, while crucial for treating infections, can disrupt the gut microbiome and lead to adverse effects.
  • Previous research indicates a link between the gut microbiota and brain function, including neurogenesis and cognitive processes.

Purpose of the Study:

  • To investigate the impact of antibiotic-induced gut dysbiosis on hippocampal neurogenesis and memory retention in adult mice.
  • To explore the potential of gut flora reconstitution, probiotics, and exercise in mitigating these antibiotic-induced deficits.
  • To elucidate the role of specific immune cells, particularly Ly6C(hi) monocytes, in mediating these effects.

Main Methods:

  • Adult mice were treated with antibiotics, followed by interventions such as specific pathogen-free (SPF) gut flora reconstitution, probiotic supplementation, or access to a running wheel.
  • Neurogenesis and memory retention were assessed using established behavioral and histological techniques.
  • Flow cytometry was used to quantify Ly6C(hi) monocyte populations in the brain.
  • Monocyte depletion and adoptive transfer experiments were performed to determine the causal role of Ly6C(hi) monocytes.

Main Results:

  • Antibiotic treatment significantly decreased hippocampal neurogenesis and memory retention in mice.
  • SPF reconstitution alone did not fully restore neurogenesis; however, combining SPF with exercise or probiotic supplementation did.
  • Mice undergoing these restorative interventions showed increased Ly6C(hi) monocyte numbers in the brain.
  • Depletion of Ly6C(hi) monocytes impaired neurogenesis, while their adoptive transfer rescued antibiotic-induced deficits.

Conclusions:

  • Antibiotic-induced gut dysbiosis negatively affects hippocampal neurogenesis and memory.
  • Exercise and probiotics can partially restore these functions, with Ly6C(hi) monocytes playing a key mediating role.
  • Targeting Ly6C(hi) monocyte populations may offer a therapeutic strategy to counteract the neurological side effects of antibiotic treatment.

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