BDNF, tryptophan and 'Peace, a way of thinking' - may be based in our way of eating too.

Interview by Michael Nehls included and info about the kynurenine pathway.

The screenshot below shows the role of new cell formation within our hippocampus - it is our active daily memory and planning center, and our ability to grow new hippocampal cells helps us to be able to keep forming and remembering new thoughts - roughly. The cells formed during adult hippocampal neurogenesis are called ‘Index-Neurons’. Our capacity for thinking is supported by the Index-neurons acting as a source of mental energy which helps us have psychological resilience and rational compassion. Our hippocampus is also helping us be curious about our experiences and to show individuality and creativity.

Watch the video (or keep reading and get back to it): What does the brain need to think peace? Michael Nehls, MD PhD at IC Forum 2024, Switzerland [International Cooperation Forum]

In typical aging the hippocampus doesn’t shrink much each year. In conditions such as Chronic Exhaustion, Major Depression, Anxiety Syndromes, and Alzheimer’s dementia, the hippocampal shrinkage rate might be 1.2-1.4% and add up over many decades to the dysfunction seen later in life.

What helps protect the hippocampus from shrinking and helps it grow more hippocampal cells instead? . . . BDNF

“In the adult hippocampus, BDNF is critical for maintaining adult neurogenesis. Adult hippocampal neurogenesis is involved not only in memory formation and learning ability, but also mood regulation and stress responses. Accordingly, decreased levels of BDNF, accompanied by low levels of adult neurogenesis, occurs in brains of older adults with impaired cognitive function and in those of patients with major depression disorder. Therefore, elucidating the mechanisms that maintain hippocampal BDNF levels is biologically and clinically important. It has been revealed that signalling from peripheral tissues contribute to the regulation of BDNF expression in the brain across the blood–brain barrier. Moreover, recent studies indicated evidence that neuronal pathways can also be a mechanism by which peripheral tissues signal to the brain for the regulation of BDNF expression.” (Amagase, et al., 2023)

BDNF activity in the brain has been linked to butyrate producing species in the gut microbiome via vagus nerves interactions. Pudding can help make us happy because of the resistant starch feeding gut microbiome species that support a happy and healthy brain.

*This post is the third in a series but I was working on two at the same time it appears. Post 1: (Substack)

Niacin adequacy is protective in part by increasing BDNF

Post 2 is also somewhat focused on the gut microbiome but with exercise as a key point. (Substack)

BDNF & anti-depressant effects are linked with butyrate producing gut microbiome species ... and both are linked with exercise.

The rest of this post wanders a bit and would be better off combined with the one above - I must have forgotten I had this one in the works because there is overlap with the Brave AI summaries I linked below. This post focuses on the kynurenine pathway, which uses tryptophan for something other than serotonin production. It is more desirable to avoid the kynurenine pathway and reducing inflammation is the way to do that. It is triggered by inflammatory cytokines and TNF.

Stress and inflammation are the triggers for shunting tryptophan down the kynurenine pathway instead of towards serotonin production. Inflammatory cytokines IL-1 and IL-6 and TNF will activate the Idoleamine 2, 3 Dioxygenase (IDO) enzyme and stress/daytime activity cortisol will activate the Tryptophan Dioxygenase (TDO) enzyme. See screenshot below.

BDNF and the gut microbiome

Bidirectional effects are seen with BDNF knockout mice have a different microbiome than wildtype mice (lack of BDNF leading to a changed microbiome) and the microbiome seems able to affect levels of BDNF in the brain, possibly from postbiotic short chain fatty acids like butyrate, or from effects on the kynurenine pathway and its breakdown of tryptophan, which leads to lower serotonin production. See graphic and video below.

“The gut microbiome’s modulation of BDNF may occur through changes in neurotransmitter function, such as the kynurenine pathway, or alterations in the availability and actions of short-chain fatty acids (SCFAs) in the brain (The Gut-Brain Axis, BDNF, NMDA and CNS Disorders).” (Brave AI summary)

Screenshot from a video embedded below.

Two enzymes can change tryptophan into kynurenine, which is diverting it away from serotonin production - leading to a person who has more anxiety and less calm within their brain. Do we need to ‘think’ our way to peace? or do we need to eat our way to having peaceful thoughts?

Nutshell - zinc, resistant starch, and pomegranate peel can help support our having butyrate producing species in our gut microbiome. Eating probiotic foods may help, reducing stress levels is a need and exercise helps. I did exercise more the last two days, but going slow to get back into shape is important - those myokines that can increase BDNF levels (second post in this series), also have types that increase inflammation.

Polyphenols can help with post exercise recovery. A drop in immune function can occur. It does feel like I have now caught a bit of a cold, so I will have to pace myself a bit better regarding rebuilding my activity level and muscle strength. I am feeling my age this year. Or feeling the error of messing with autoimmune disease. I should have remained off of animal products it seems.

~~~ AI summary info below which is also in the other BDNF and exercise post with additional info about butyrate producing species. The rest of this post is kind of redundant - copy/paste material that I didn’t look into further at this time.

Impact of BDNF on the Gut Microbiome

• BDNF has been shown to influence the gut microbiome’s composition and function. For example, BDNF knockout mice (BDNF+/- group) had a significantly different gut microbiota profile compared to wild-type mice (BDNF+/+ group) (Brain-derived neurotrophic factor preserves intestinal mucosal barrier function and gut microbiota in mice).

• BDNF may play a role in maintaining the integrity of the intestinal mucosal barrier, which enables the intestine to contain luminal microorganisms and molecules while preserving nutrient absorption (Brain-derived neurotrophic factor preserves intestinal mucosal barrier function and gut microbiota in mice). (Brave AI summary)

Follow-up question: What specific gut bacterial strains are most closely linked to bdnf regulation and expression?

Based on the provided search results, the following gut bacterial strains are mentioned as being linked to BDNF regulation and expression:

• Lactobacillus strain: Ingestion of a specific Lactobacillus strain regulates emotional behavior and central GABA receptor expression in mice via the vagus nerve (Proc Natl Acad Sci USA 108, 16050–16055, 2011).

Associated with Reduced hippocampal BDNF expression: “Prevotella, Bacteroides, and Parabacterioides: Fecal microbiota transplantation from aged rats into young rats altered the gut microbiota composition, with pronounced increases in these bacterial populations, which was associated with decreased hippocampal BDNF expression (IJMS).” (Amagase, et al., 2023)

While the search results do not provide a comprehensive list of specific gut bacterial strains linked to BDNF regulation and expression, these strains are mentioned as having a potential impact on hippocampal BDNF expression. Further research is needed to fully elucidate the specific strains and their mechanisms of action.

Context for “What specific gut bacterial strains… & BDNF”

1. www.ncbi.nlm.nih.gov, Probiotic modulation of the microbiota-gut-brain axis and behaviour in zebrafish - PMC

2. www.sciencedirect.com, Brain-derived neurotrophic factor preserves intestinal mucosal barrier function and alters gut microbiota in mice - ScienceDirect

3. Amagase Y, Kambayashi R, Sugiyama A, Takei Y. Peripheral Regulation of Central Brain-Derived Neurotrophic Factor Expression through the Vagus Nerve. Int J of Molecular Sciences. 2023; 24(4):3543. https://doi.org/10.3390/ijms24043543 www.mdpi.com, (Amagase, et al., 2023)

Follow up question rephrased by me

Butyrate producing gut microbiome species and bdnf modulation pubmed

Based on the search results, the following key findings are highlighted:

• Faecalibacterium prausnitzii and Eubacterium rectale, recognized butyrate-producing species in the human gut, were reduced in individuals with Myalgic Encephalomyelitis/Chronic Fatigue Syndrome (ME/CFS) [1].

• Butyrate has been shown to protect the brain and enhance plasticity in neurological disease models, suggesting a potential role in modulating brain-derived neurotrophic factor (BDNF) levels [2].

• Supplementation with butyrate, a short-chain fatty acid (SCFA), can raise BDNF levels by inhibiting histone deacetylase and maintaining chromatin relaxation in the hippocampus [3].

• Additionally, butyrate may also inhibit the secretion of pro-inflammatory cytokines, which can interfere with BDNF expression.

These findings collectively suggest that butyrate-producing gut microbiome species, particularly Faecalibacterium prausnitzii and Eubacterium rectale, may play a role in modulating BDNF levels through the production of butyrate. Further research is needed to fully elucidate the mechanisms underlying this relationship.

References:

[1] Deficient butyrate-producing capacity in the gut microbiome is associated with bacterial network disturbances and fatigue symptoms in ME/CFS, (pubmed.ncbi.nlm.nih.gov)

[2] Butyrate, neuroepigenetics and the gut microbiome: Can a high fiber diet improve brain health? (sciencedirect.com)

[3] Modulating Gut Microbe Populations to Generate More Butyrate, thus Raising BDNF Levels and Improving Cognitive Function, (fightaging.org)

Context

1. pubmed.ncbi.nlm.nih.gov, Deficient butyrate-producing capacity in the gut microbiome is associated with bacterial network disturbances and fatigue symptoms in ME/CFS - PubMed

2. www.sciencedirect.com, Butyrate, neuroepigenetics and the gut microbiome: Can a high fiber diet improve brain health? - ScienceDirect

3. www.fightaging.org, Modulating Gut Microbe Populations to Generate More Butyrate, thus Raising BDNF Levels and Improving Cognitive Function – Fight Aging!

4. www.frontiersin.org, Frontiers | Role of Butyrate, a Gu

Context for BDNF and Gut Microbiome

1. www.researchgate.net, (PDF); www.ncbi.nlm.nih.gov, The Gut-Brain Axis, BDNF, NMDA and CNS Disorders. - NCBI

2. www.ncbi.nlm.nih.gov, Brain-derived neurotrophic factor preserves intestinal mucosal ...

3. www.nature.com, Gut microbiota modulate neurobehavior through changes in brain insulin sensitivity and metabolism | Molecular Psychiatry

4. www.nature.com, Probiotic modulation of the microbiota-gut-brain axis and behaviour in zebrafish | Scientific Reports

5. jneuroinflammation.biomedcentral.com, Impact of microbiota on central ner

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