Critical illness, including severe COVID, often lead to long term cognitive and mental
health complications. Current non-pharmacological interventions, including ABCDEF bundle,
are of limited efficacy. The largest psychological intervention trial to date also
demonstrated no beneficial effect. These impairments may persist for years and are
associated with chronic pain, impaired physical functioning, decreased quality of life,
increased use of psychotropic medications, opioid abuse, self-harm, and increased acute
care service utilization. Half of previously employed critical illness survivors,
including those with long COVID, are not able to return to work a year later resulting in
loss of insurance and difficulty in seeking professional help.

Increasing recognition that the nervous system and the gastrointestinal tract are
communicating through a bidirectional network of signaling pathways, collectively known
as the gut-brain-axis, resulted in emergence of a novel discipline of "nutritional
psychiatry" advocating that diet and nutrition may be central determinants of both
physical and mental health. In the outpatient setting, fiber rich Mediterranean style
diet has been linked to improvements in cognitive and mood symptoms possibly via its
known anti-inflammatory effect whereby diets high in sugars and refined grains with high
inflammatory potential have been linked to the development of depression.

Critical illness and associated interventions lead to the loss of normal gut bacteria,
allowing overgrowth of disease-promoting pathogenic bacteria resulting in severe
dysbiosis. During dysbiosis, gut-brain pathways are dysregulated resulting in
neuroinflammation, anxiety and depressive-like behaviors as well as cognitive impairment.
Dysbiosis can persist months after the resolution of critical illness. Restoration of
healthy microbiome may thus be key to facilitating psychiatric and cognitive recovery
after critical illness.

Can the Mediterranean diet be used to restore microbiome diversity in this population?
Perhaps not right away, as critical illness survivors have significant decrease in fiber
degrading bacterial organisms. Others demonstrated that high-fiber diet alone does not
result in increased microbial community diversity. What about probiotics? In patients
with antibiotics-associated dysbiosis, probiotics induced a persistently incomplete
indigenous stool microbiome recovery. How can microbiome diversity be restored? Fermented
foods may be the most promising approach. Consumption of fermented milk facilitated
restoration of gut homeostasis in patients with irritable bowel syndrome and increased
their "feeling good" scores. Other human intervention studies using fermented tea,
sauerkraut, fermented plant extract, kimchi, and fermented soybean milk reported
increased presence of bacteria in the gut known for their health promoting properties.
Consumption of fermented foods was associated with positive modulation in brain activity
and fewer symptoms of social anxiety. A 10-week high fermented food diet intervention
demonstrated increased microbiota diversity and decreased inflammatory markers among
healthy volunteers. Can it be applied to survivors of critical illness including COVID to
help them recover from dysbiosis and inflammation, and improve their mental health and
other outcomes?

Specific Aim #1: to evaluate feasibility of high fermented food diet among critical
illness survivors and its effect on microbiome diversity Hypothesis 1a: critical illness
survivors will tolerate high fermented food diet Hypothesis 1b: high fermented food diet
will increase microbiome diversity in critical illness survivors.

Specific Aim #2: to evaluate the effect of high fermented food diet on immune system
performance and recovery, mental health, cognition, and quality of life of critical
illness survivors.

Hypothesis 2a: high fermented food diet will improve immune system performance among
critical illness survivors.

Hypothesis 2b: critical illness survivors treated with fermented food diet for 3 months
will have a reduction in symptoms of anxiety, depression and acute stress/PTSD Hypothesis
2c: critical illness survivors treated with fermented food diet for 3 months will have
improvement in cognition.

Hypothesis 2c: critical illness survivors treated with fermented food diet for 3 months
will have improvement in quality of life.