A metabolic "double hit" in prefrontal gray and white matter shapes microbiota-related visual learning memory

Xiaodong Song1, Dong Huang1, Shilin Liu1

  • 1Department of Psychiatry, First Affiliated Hospital, Jinan University, Guangzhou, 510630, China.

Abstract

Insights

Major depressive disorder (MDD) involves visual memory deficits linked to gut bacteria like Ruminococcus. Brain metabolism in gray and white matter, influenced by Ruminococcus, exacerbates these memory issues in MDD patients.

Area of Science:

  • Neuroscience
  • Microbiology
  • Psychiatry

Background:

  • Visual learning memory deficits are a core issue in major depressive disorder (MDD).
  • The specific gut microbiota contributing to these deficits and their interaction with brain neurochemistry are not fully understood.
  • Gut dysbiosis and frontolimbic metabolic alterations are associated with MDD, but the role of regional neurochemistry in the gut-brain-cognition axis is unclear.

Purpose of the Study:

  • To investigate the relationship between gut microbiota, neurochemical changes in the anterior cingulate cortex (ACC) and prefrontal white matter (PWM), and visual learning memory deficits in MDD patients.
  • To explore how neurochemical ratios (NAA/Cr, Cho/Cr) in the ACC and PWM modulate the association between gut microbiota and cognitive function in MDD.

Main Methods:

  • Assessed visual learning memory using the Brief Visuospatial Memory Test-Revised in 38 MDD patients and 41 healthy controls (HC).
  • Analyzed fecal gut microbiota composition using 16S rRNA gene sequencing.
  • Quantified neurochemical ratios (N-acetylaspartate/Creatine [NAA/Cr] and Choline/Creatine [Cho/Cr]) in the ACC and PWM via proton magnetic resonance spectroscopy.

Main Results:

  • MDD patients showed visual learning memory deficits, with elevated right ACC NAA/Cr and reduced right PWM NAA/Cr compared to HC.
  • Ruminococcus abundance was higher in MDD patients and negatively correlated with visual learning memory.
  • The negative association between Ruminococcus and memory was moderated by ACC and PWM NAA/Cr ratios, particularly when ACC NAA/Cr was high and PWM NAA/Cr was low.

Conclusions:

  • A "double hit" of simultaneous gray matter (ACC) and white matter (PWM) metabolic dysregulation exacerbates Ruminococcus-associated visual learning memory impairment in MDD.
  • Distinct yet interconnected vulnerabilities in gray and white matter neurochemistry critically shape microbiota-cognition associations within the MDD context.
  • These findings highlight the complex interplay between gut microbiota, brain metabolism, and cognitive function in major depressive disorder.

Related Concept Videos

Gut-Brain Axis01:22

Gut-Brain Axis

The gut–brain axis is a bidirectional communication system that connects the gastrointestinal tract and the brain. This interaction is mediated through multiple pathways, including the vagus nerve, hormonal signals, immune responses, and chemical messengers produced by gut microbes.Microbial Contributions to Brain FunctionGut microbiota contributes significantly to brain function by producing neuroactive compounds. These include neuroactive compounds that influence neurotransmitters such as...
Long-term Depression01:03

Long-term Depression

Long-term depression, or LTD, is one of the ways by which synaptic plasticity—changes in the strength of chemical synapses—can occur in the brain. LTD is the process of synaptic weakening that occurs over time between pre and postsynaptic neuronal connections. The synaptic weakening of LTD works in opposition to synaptic strengthening by long-term potentiation (LTP) and together are the main mechanisms that underlie learning and memory.
Calcium Ion Concentration Mechanism
If over time, all...
Long-term Depression01:05

Long-term Depression

Long-term depression, or LTD, is one of the ways by which synaptic plasticity—changes in the strength of chemical synapses—can occur in the brain. LTD is the process of synaptic weakening that occurs over time between pre and postsynaptic neuronal connections. The synaptic weakening of LTD works in opposition to synaptic strengthening by long-term potentiation (LTP) and together are the main mechanisms that underlie learning and memory.
Dysbiosis of the Gut Microbiota01:18

Dysbiosis of the Gut Microbiota

The human gut microbiome includes a diverse array of microbial species, including beneficial commensals and opportunistic pathogens, which interact to support host health. These microbes contribute to essential functions such as nutrient metabolism, immune system modulation, and maintenance of intestinal barrier integrity. However, disruptions to this equilibrium—referred to as dysbiosis—can have widespread physiological consequences.Dysbiosis is often characterized by reduced microbial...
Depression: Overview01:18

Depression: Overview

Depression is a prevalent mental illness marked by persistent sadness and lack of interest in previously enjoyable activities. It can take several forms, including major depression, persistent depressive disorder, and bipolar I and II disorders. Symptoms range from emotional changes like chronic worry to physical changes like sleep disturbances and suicidal thoughts. From a neurobiological perspective, depression is believed to be triggered by abnormalities in the brain's prefrontal cortex,...
Microbiota Modulation by Antibiotics01:21

Microbiota Modulation by Antibiotics

Antibiotics have revolutionized modern medicine by saving countless lives from bacterial infections. However, their widespread use has inadvertently harmed the delicate balance of the human gut microbiota. The gut microbiota, a complex community of bacteria, archaea, viruses, and fungi, plays a vital role in regulating metabolism, immune responses, and maintaining intestinal health. Antibiotics, especially broad-spectrum types, disrupt this ecosystem by eradicating both harmful and beneficial...