I’ve said a couple of times now that the theory seems to account for adult-onset language disorders, mentioning stroke and dementia specifically, but I haven’t gone into any more detail about what I think is happening. The truth is, I’m not sure. I only really know about child development. I need outside perspectives to help me with it. It’s an important potential source of verification for the theory though, and compared with brain imaging studies, it’s low-hanging fruit. So I’ve started investigating. My investigations sent me in an unexpected direction though.
Thanks to my friend Mat Brown, I found myself here, an article on the King’s College London website, which discusses some new (December 2023) research that supports the idea that having a non-diverse gut microbiome brings about cognitive decline in Alzheimer’s.
I believe that the original work identifying this connection is this one. I’m pleased to note that these authors are keen to stress the bidirectionality of the relationship in the gut-brain axis.
I wanted to look into it in a bit more detail, but I also didn’t want to do any work, so I asked ChatGPT4. Below is its response, lightly edited. It should get us up to speed on some relevant aspects of current thinking around the microbiome.
The human microbiome, particularly the gut microbiome, plays a critical role in health and disease. It influences numerous physiological processes, including metabolism, immune function, and even brain function and behavior through the gut-brain axis. Research into the microbiome’s impact on normal development and various diseases, including Alzheimer’s Disease (AD) and Autism Spectrum Disorder (ASD), has revealed significant insights, though this field is still in its early stages, and much remains to be discovered.
Normal Development
In normal development, the gut microbiome begins to establish immediately after birth and undergoes significant changes in composition and function during the first few years of life. This early period is critical for the development of the immune system, metabolism, and even the central nervous system. A healthy, balanced microbiome in early life is associated with a reduced risk of many chronic conditions, including obesity, diabetes, and asthma.
Alzheimer’s Disease (AD)
- Composition Differences: Individuals with Alzheimer’s disease tend to have a different composition of the gut microbiome compared to healthy elderly individuals. There is often a decrease in microbial diversity and a dysbiosis condition, characterized by an imbalance in the beneficial and harmful bacteria. Specifically, increases in pro-inflammatory bacteria and decreases in anti-inflammatory or protective bacteria have been observed.
- Accounting for Differences: […]it is hypothesized that factors such as diet, lifestyle, genetics, and exposure to antibiotics could play roles.
- Changes in Function: In the context of AD, the gut microbiome might contribute to the disease’s progression by enhancing systemic inflammation, altering the integrity of the blood-brain barrier, and affecting the production and aggregation of amyloid-beta, a hallmark of AD pathology.
Autism Spectrum Disorder (ASD)
- Composition Differences: Like AD, ASD is associated with alterations in the gut microbiome. Children with ASD often exhibit reduced microbial diversity and an imbalance in specific bacterial taxa. For instance, some studies have reported an increase in Clostridium or Desulfovibrio species and a decrease in beneficial species such as Bifidobacteria.
- Accounting for Differences: The reasons for these differences are likely multifactorial, involving genetics, environmental exposures (such as prenatal and postnatal antibiotic use), and diet. There is also a hypothesis that gut microbiome alterations in ASD might be linked to gastrointestinal (GI) issues commonly reported in ASD, which could further modify the gut environment and microbial composition.
- Changes in Function: The functional changes in the gut microbiome associated with ASD may include altered metabolic profiles, such as differences in the production of short-chain fatty acids (SCFAs) and other metabolites that can influence gut health, immune function, and, potentially, neurobehavioral outcomes. There is also evidence suggesting that the gut microbiome in ASD might affect the gut-brain axis, potentially influencing symptoms of the disorder.
General Considerations
It’s important to highlight that while the associations between the microbiome and diseases like AD and ASD are compelling, they do not yet prove causation. […]
Chat GPT4, in response to: “Could you try to characterise science’s current understanding of the microbiome in normal development, versus in Alzheimer’s, versus in ASD. As we understand it: how do they differ in composition; what accounts for these differences; what changes in the ‘function’ of the microbiome might an individual experience?”
Discussion
I’m not about to make any strong statements about the microbiome and ASD / AD, not least because I have a dangerously minimal amount of knowledge in this area. I need to fully understand what the scientists are currently saying about the bidirectional relationship between the brain and the microbiome before I can know if I’ve got something new here. With that as a caveat then…
What ASD and AD have in common, under the ICDT, is that they are characterised by a lack of effective communication between the social domain and the wider semantic system. Taken alongside the reported changes in the biome in AD and our current understanding of the biome in ASD, the theory suggests something startling – the more integrated the processing is in the brain, the more diverse will be the microbiome in the gut.
The theory also suggests a way of understanding this relationship. I take the level of integration of the social domain as the source of the effect here, but the same should apply to any aspect of brain function that is implicated in the production of hormones. Before we move on, please check out the following paper:
- Co-regulation brings about a hormonal response in the infant. They specifically mention oxytocin, cortisol, and alpha-amylase. Coregulation: A multilevel approach via biology and behaviour. (In Children, MDPI, Aug. 2023).
Unintegrated children are subject to hormones such as oxytocin as a result of co-regulation, as we all are. Warm, positive social thoughts about others will probably stimulate some kind of hormonal response as well. Possibly a feeling of security and familiarity does so too, to a lesser degree. For the rest of their day, the system isn’t firing.
Integrated children, when they make discoveries, refine an action, or develop an enhanced understanding in a given area, refer a summary of this semantic update up to the subconcept ME in the social domain. As they update their self-image with this new enhancement in their ability to function within the world, they are delivered a hormonal reward. In this way, an increase in mental ability is rewarded by the brain. This type of feedback is not available to the unintegrated child, who produces less of the hormones as a result.
My next thought was to look for evidence that certain types of bacteria in the microbiome bloom in response to certain hormones. It’s there, but you have to look for it.
- A review of current research, showing that “hormones impact many aspects on bacteria, such as the growth, metabolism, and virulence [sic]”. The orchestra of humanbacteriome by hormones. (In Microbial Pathogenesis, Elsevier, Jul 2023). The review is badly translated. It doesn’t mention any of the above hormones.
Most researchers are busy talking about the upstream impact of the microbiome on hormones (and on everything else under the sun). I think we need to turn that on its head and consider the role that integrated cognitive functioning has on hormone production, and the role that hormone production has on the microbiome. It is a bidirectional relationship, after all.
This would seem to predict that the microbiome would be less diverse as a result of stroke. I asked ChatGPT4.
Changes in Microbiome Composition after Stroke
After a stroke, patients often experience alterations in their gut microbiome composition. Research has shown shifts towards a dysbiotic state, characterized by reduced microbial diversity and an imbalance in the relative abundance of certain bacteria. Specifically, increases in opportunistic pathogens and decreases in beneficial commensal bacteria have been observed. These changes are thought to contribute to post-stroke complications such as infections and impaired recovery.
ChatGPT4, in response to: “is there any evidence regarding how the microbiome is affected after stroke?”
I don’t think anyone is arguing that stroke is caused by the microbiome, but I wouldn’t be surprised.
Trying to look for an effect in 2 year olds is challenging. Lots of processes are at play, including a shifting diet. Furthermore, maybe the effect wouldn’t be too dramatic, as it is proposed to arise when personal cognitive achievements are socially mediated, and these come when they come – they’re certainly not queued up at the door of the social domain, awaiting admittance. My research brought me here:
This has some interesting graphics that depict the relative abundance of certain bacteria in the microbiome during normal development, like this one.
There seems to be an increase in bacteroidacaae at around the time in question. It’s possible then that bacteroidacaae have receptors for the likes of oxytocin, cortisol, and alpha-amylase. The next question is whether bacteroidacaae is found to be reduced in ASD and AD. In fact it seems it is actually more abundant in ASD. All this proves is that I’m not the one to do this research.
Incidentally, I say that integration happens at 2 years in my recent post and above. My personal understanding is that it is usually between 18 and 24 months – I just say 2 years for clarity. Not that any of this is clear.
