Serrano Journal Club 1

Paper: Gut Microbiota in dementia. Critical review of novel findings and their potential application – Luc, Misiak, Pawlowski, et al 2020

What are the main points – 

1. Gut Microbiome is linked with dementia and Alzhemiers 
2. Infectious agents linked with dementia – herpes, H pylori, bacteria causing gingivitis
3. Supplement with lactobacillus and bifidobacterium probiotics may help prevent dementia
4. TMAO is bad
5. Cold therapy may be a modality to reduce inflammation   

What are the general findings – 

1. None – this is a review

Summarize in your own words – 

1. This review supports the narrative that dementia, specifically alzheimer’s, is the result of chronic inflammation. One of the primary drivers of chronic inflammation is gut dysbiosis. By augmenting the gut microbiome and correcting dysbiosis there is likely going to be a reduction in cognitive decline. 

Compare this information to existing understanding of the topic (what’s new, different, contrary to your previous understanding of the topic – 

1. Different – they continue to state that fat intake is tied to TMAO – my understanding is it’s related to choline, betaine and carnitine 
2. Contrary – no mention of diet to modulate inflammation outside of lower animal protein and fat. They used mice models to support this information. No mention of the lymphatic system and its impact on neuroinflammation. This may be assumed to be included in the “bloodflow system.” I don’t think they mentioned anything about environmental toxins. 
3. New – need to investigate primary vs secondary bile acids. 

What conclusion do you come to based on the information and why – 

1. Inflammation, as a broad term, contributes to cognitive impairment. There are ways to modulate chronic inflammation. The use of cold therapy and probiotics may lower the risk of dementia. Decreasing intestinal permeability will likely reduce the risk in developing dementia.   

What findings would you share with your audience, apply practically – 

1. Consider cold exposure – cryo or just reduced temperature to decrease inflammation. I would use this more as an adjunct in lifestyle management. 
2. I think the 5R program is still probably a more comprehensive management tool to reduce IP. 

Notes: 

• Current RF for cognitive decline – insulin resistance, obesity, chronic low-grade inflammation 
• AD – caused by abnormal processing of amyloid B and tau – both mediated by glycogen synthase kinase 3B (GSK3B) conditions of insufficient insulin signaling ie insulin resistance
• Gut inflammation/intestinal permeability leads to BBB permeability 
• Vagus nerve and blood circulation considered to be routes of influence – no mention of lymphatics 
• Gut microbiome produces NT – GABA, ACh, dopamine, serotonin, vitamins, toxins
• Variance in fecal ammonia or lactic acid for those with and without dementia – Saji et all 2020
• LPS may feed accumulation of AB and vice versa 
• Bacteroides is lower in dementia patients 
• TMAO elevated in CSF in MCI and AD 
• Calprotectin elevated in AD
• Use zonulin to assess intestinal permeability 
• Whole body cryotherapy – decreases inflammation, increases bile acid production – consider use in dementia 
• Stress leads to dysbiosis 
• There is primary produced bile acids and secondary produced bile acids
  • Increased DCA:CA ratio associated with cognitive decline 
• Low initial BMI may be risk factor for dementia 
• FMO3 expression linked to impact of TMAO and atherosclerosis