Neuroinflammatory remodeling of the anterior cingulate cortex as a key driver of mood disorders in gastrointestinal disease & disorders, 2021, Matisz

Highlights

• Clinical literature reveals gastrointestinal diseases and disorders are associated with reduced cortical thickness, increased activity and metabolism, and altered functional connectivity of the anterior cingulate cortex.
• Preclinical studies reveal gut inflammation drives neuroinflammation, and remodelling of neuronal structures including the ACC.
• The ACC network provides a context (schema) in which to interpret internal (e.g. pain) and external (e.g. threats) stimuli.
• We propose chronic gut dysfunction drives neural remodeling that biases the ACC network towards a negative schema, driving physiological responses towards non-existent or anticipated threats.
• This negative schema promotes an imbalance between parasympathetic and sympathetic nervous system responses, in turn perpetuating and exacerbating gut dysfunction.

Abstract
Most gastrointestinal diseases and disorders (GIDD) are associated with depression, anxiety, and cognitive dysfunction. This suggests that shared features of GIDD, particularly chronic pain and inflammation, affect specific neural targets. The critical review of clinical and animal research presented here reveals that anterior cingulate cortex (ACC) is a primary target. It is particularly sensitive to neuroinflammation, and its function accounts for altered mental function emergent in GIDD.

We propose that peripherally-triggered neuroinflammation normally signals injury/illness to ACC, which increases threat assessment and pain sensitivity to cope with increased vulnerability. Chronic peripheral inflammation over-drives this process, leading to long-term ACC structural remodeling, and excessive threat signaling. This evokes anxiodepressive phenotypes even without direct evidence of threats because ACC utilizes schemas to infer affective outcomes (e.g. pain) based on complex contextual information. This activates the autonomic nervous system, exacerbates immune dysfunction, and promotes further gut pathology.

This theory provides a mechanistic account of bidirectional interactions among gastrointestinal, immunological, and neural systems in GIDD, and is likely applicable to other chronic inflammatory conditions.

Paywall, https://www.sciencedirect.com/science/article/abs/pii/S0149763421005686

 

What's "bidirectional" here? The neurological response appears consistent with being an effect, not a cause or even factor. Sickness response is indistinguishable from "anxiodepressive phenotypes" to an outside observer, especially so on questionnaires that deliberately conflate the concepts. There is only some assumption that the brain effects somehow must drive back as a cause, which has no basis here.

It really seems like research is honing in on how significantly the microbiome affects overall health and can bring predictable illnesses, yet can't bring itself to separate cause-and-effect since it's always been asserted the other way around, or fully independent of an actually physical changes, which changes in the microbiome contradict. It was only recently that this could be assessed and the claims of a "bidirectional" process have been made for far longer than that, so they're made more out of tradition than anything.

None of which should be surprising, it's an organ teeming with both pathogens and immune cells, constantly challenged by added pathogens and availability of nutrients. It also produces all the micronutrients the body uses, obviously affecting all health. But since the psychosomatic model has dominated for too long, it has to be thrown into the mix for no discernible reason.