Nature Review Series Annual Review: Three Breakthroughs in Gut-Brain Axis Cognition Released in 2022!

*For medical professionals only

In 2016, the Rome IV diagnostic guidelines renamed "functional gastrointestinal disorders" to "entero-brain interaction disorders", affirming the key role of the gut-brain axis in human health, and in recent years, the gut-brain axis as an emerging research field, the number of studies has soared, and multiple pathways have been revealed
.
In 2022, there are some "phenomenal studies" published in top journals, which give us a deeper understanding
of the gut-brain axis.

As a result, the journal Nature Reviews Gastroenterology & Hepatology published an annual review [1], focusing on three advances in the gut-brain axis published in 2022, involving neural pathways for thirst and satiety after drinking [2], and regulators of switching between eating and courtship behavior [3] and the relationship between enterovirome and cognitive function[4].

The first study was published in In Nature [2], researchers at the California Institute of Technology looked at the direct neural connections
between the gut and the brain.
In general, several direct pathways exist, including vagus afferents in ganglion cells with bidirectional projection, sensory neurons in the dorsal root ganglia of the gut and spinal cord, and communication between vagus and sympathetic efferent fibers and target cells in the gut
.
These pathways either innervate the enteric nervous system (ENS) or transmit information
directly from intestinal cells.

The researchers analyzed the role
of the vagus nerve in thirst and drinking behavior.
Previously, while the vagus nerve was known to play an important role in nutrient perception and appetite regulation, including water intake, the mechanism by which it perceives osmotic pressure and relays information to the brain was largely unknown
.

Using the recording of light and electrical signals from vagus neurons in mice, the researchers found that satiety after thirst and drinking was transmitted through the vagus nerve through the vagus nerve to the forebrain region
involved in thirst.
A subpopulation of vagus neurons is always activated by water injection in the intestines, not the stomach
.
This subpopulation is a neuron in the vagus ganglia that expresses tachykinin-1 and projects to HPA
.

Surgical or chemical denervation of the vagus nerve has shown that HPA plays a central role
in transmitting signals of thirst and satiety after drinking water to the brain based on osmolality.

Further research showed that HPA vagus afferents are not sensitive to changes in osmolality itself, but rather are partially in response to water-induced vasoactive intestinal peptide (VIP), a molecule that may have been released by
intestinal neurons.

The results of this study have considerable implications not only for our understanding of the homeostatic mechanisms behind thirst and satiety after drinking water, but also for understanding how disorders in the gut-brain axis affect this important physiological function, highlighting the complex function of the vagus nerve and the role
of vagus innervation in directing gut-brain communication.

In the second study, also published in Nature, researchers at the University of California, San Diego revealed an endocrine communication mechanism that transmits information through the circulatory system to the brain after the
gut releases hormones and neuropeptides.

The study was conducted in fruit flies, and the researchers analyzed the effects of specific food groups on feeding and courtship behavior in fruit flies, because the ability to switch between feeding and courtship is important for evolutionary adaptation, and animals in nature need to balance feeding to ensure survival and courtship to ensure the timing
of reproduction.

The researchers fasted male flies for 24 hours, then resumed feeding, and then placed them with female flies, interestingly, if they were fed protein, they turned to courtship behavior, but not sucrose
.

Mechanistic studies have shown that the shift in fruit flies to courtship behavior is mediated by activating enteroendocrine cells to produce diuretic hormone 31 (DH31), while amino acids are able to increase levels of DH31 in the circulatory system, and DH31 released from the intestine activates specific subsets of neurons in the brain, including neurons that produce corazonin, a neuropeptide found in invertebrates, similar to gonadotropin-releasing hormone in mammals.
The neurons that produce corazonin are involved in the reproductive behavior
of fruit flies.

The elimination of DH31 receptors in the brain inhibited the switch
from feeding to courtship behavior in fruit flies.

This is the neurological mechanism
by which fruit flies turn to courtship behavior after feeding proteins.
This mechanism highlights the influence
of specific nutrients on neuronal activity and behavior.

In the final study, published in Cell Host & Microbe, the Spanish team described the effects
of the gut virus group on cognitive function.

Studies have generally found that the composition of gut microbes is influenced by food, which in turn affects behavior, but the neurological mechanisms are not well understood, and fungi and viruses have been
poorly studied in addition to gut bacteria.
In fact, the number of viruses in the human gut is at least equal to that of bacteria, of which about 90% are bacteriophages
.

In the new study, increased levels of specific orders of bacteriophages in the human gut were associated with abundance of specific species of bacteria, as well as performance on cognitive tests, for example, people with higher levels of the order Ceraciformes and Longtail Phages also had higher levels of Lactococcus, Lactobacillus, and Streptococcus species and performed better on central executive processing tasks
, while those with higher levels of Microphage Family were more severely impaired executive function.

Brain transcriptome analysis in mice and fruit flies showed an association between the level of the order Caudiforma and the long-tailed phage family and the expression of neural genes, which are most closely associated with the expression of genes involved in synaptic plasticity, neural activity, and neuronal development
.
Based on these results, the researchers concluded that phage balance is an important additional factor
in the influence of diet and microbiota on the gut-brain axis.

Various ways of communication between the gut and the brain

These three studies, along with many published in 2022, suggest that the communication pathway between the gut and brain is an emerging area of research
.
As research into the genome, transcriptome, proteome, and metabolome increases, we have the opportunity to learn more about the mechanisms
of the gut-brain axis.
In the future, there will be more comprehensive ways to study the interactions
between the physiological functions of various organs and gut microbes.

References:

[1] Hao M M, Stamp L A.
The many means of conversation between the brain and the gut[J].
Nature Reviews Gastroenterology & Hepatology, 2022: 1-2.

[2] Ichiki T, Wang T, Kennedy A, et al.
Sensory representation and detection mechanisms of gut osmolality change[J].
Nature, 2022, 602(7897): 468-474.

[3] Lin H H, Kuang M C, Hossain I, et al.
A nutrient-specific gut hormone arbitrates between courtship and feeding[J].
Nature, 2022, 602(7898): 632-638.

[4] Mayneris-Perxachs J, Castells-Nobau A, Arnoriaga-Rodríguez M, et al.
Caudovirales bacteriophages are associated with improved executive function and memory in flies, mice, and humans[J].
Cell Host & Microbe, 2022, 30(3): 340-356.
e8.

The author of this article Ying Yuyan