- New paper in Neuroscience & Biobehavioural Reviews can be downloaded here before May 25th 2024. After that date find it here
ABSTRACT
The evolution of the gut-microbiota-brain axis in animals reveals that microbial inputs influence metabolism, the regulation of inflammation and the development of organs, including the brain. Inflammatory, neurodegenerative and psychiatric disorders are more prevalent in people of low socioeconomic status (SES). Many aspects of low SES reduce exposure to the microbial inputs on which we are in a state of evolved dependence, whereas the lifestyle of wealthy citizens maintains these exposures. This partially explains the health deficit of low SES, so focussing on our evolutionary history and on environmental and lifestyle factors that distort microbial exposures might help to mitigate that deficit. But the human microbiota is complex and we have poor understanding of its functions at the microbial and mechanistic levels, and in the brain. Perhaps its composition is more flexible than the microbiota of animals that have restricted habitats and less diverse diets? These uncertainties are discussed in relation to the encouraging but frustrating results of attempts to treat psychiatric disorders by modulating the microbiota.
Neuroscience and Biobehavioral Reviews 161 (2024) 105653 https://doi.org/10.1016/j.neubiorev.2024.105653
Evolution and the critical role of the microbiota in the reduced mental and physical health associated with low socioeconomic status (SES)
ABSTRACT
The evolution of the gut-microbiota-brain axis in animals reveals that microbial inputs influence metabolism, the regulation of inflammation and the development of organs, including the brain. Inflammatory, neurodegenerative and psychiatric disorders are more prevalent in people of low socioeconomic status (SES). Many aspects of low SES reduce exposure to the microbial inputs on which we are in a state of evolved dependence, whereas the lifestyle of wealthy citizens maintains these exposures. This partially explains the health deficit of low SES, so focussing on our evolutionary history and on environmental and lifestyle factors that distort microbial exposures might help to mitigate that deficit. But the human microbiota is complex and we have poor understanding of its functions at the microbial and mechanistic levels, and in the brain. Perhaps its composition is more flexible than the microbiota of animals that have restricted habitats and less diverse diets? These uncertainties are discussed in relation to the encouraging but frustrating results of attempts to treat psychiatric disorders by modulating the microbiota.
Neuroscience and Biobehavioral Reviews 161 (2024) 105653 https://doi.org/10.1016/j.neubiorev.2024.105653
Reduced life expectancy and poor health associated with low Socioeconomic Status (SES)
Exposures to appropriate microorganisms from mother and family, and also from the natural environment, are an evolved necessity because they drive development of essentially all organs, including the brain, and they provide data and signals that are needed during the development of the immune system, particularly the regulatory arm of the immune system that limits chronic inflammatory disorders. Moreover these organisms populate the various microbiotas, notably in the gut.In 2014 we published a paper pointing out that these essential microbial exposures are most likely to be compromised in people of low socioeconomic status (SES).
Recently further papers from others and from me have argued that compromised microbial exposures may be responsible for much of the health deficit associated with low SES. That health deficit is enormous. In a classic review in 2012, Marmot and colleagues pointed out that life expectancy in poor versus wealthy areas of London could vary by as much as 17 years, and in Glasgow the difference was as much as 28 years. How much of this health deficit is driven by compromised microbial exposures?
The figure below provides a visual summary of the required microbial exposures, and the lifestyle factors that compromise them. It is clear that almost all these factors are closely associated with low SES.
All of these factors have been shown to modify microbial exposures, and the microbiome, as reviewed here. Obviously we are not saying that they act only via the microbiome. For example, smoking and pollution clearly exert toxic effects that are independent of changes to microbial inputs. Nevertheless, the effects of these factors on essential microbial exposures are profound.
The problem now is to discover how much of the SES-linked health deficit is attributable to changed microbial inputs. We suspect that this mechanism accounts for a rather large part of the problem, including the associations between low SES and psychiatric and neurodegenerative disorders.
One item in the panel on the right deserves further explanation. There is an image of an infant with a trigger spray of bleach aimed directly at its face. We have discussed this issue here.
There is increasing evidence that damage to epithelial barriers can accelerate entry of potential allergens into the the tissues of the gut or airways. Moreover double stranded DNA (dsDNA) appears to act as a "danger signal", and as a Th2 adjuvant. cGAS, the molecule that detects cytosolic dsDNA, appears to be essential for the development and airway allergy. Therefore damage to epithelial barriers accompanied by cell death in the airways might cause infants to develop allergic responses to allergens that happen to be present at the same time as the exposure to bleach/detergent mixtures, or to other agents with similar properties.
Exposure of infants to such cleaning agents is likely to occur in homes of low SES where the mother may be cleaning while looking after infants, whereas in wealthy homes the cleaning is done by cleaning personnel, and the infant will not usually be present.
See additional explanations of this hypothesis on the cleaning_agent page.
This is clearly an important issue and there is urgent need for research to confirm or invalidate this hypothesis. It potentially explains why some workers find that domestic cleaning is associated with allergic disorders, while other authors do not.
There is increasing evidence that damage to epithelial barriers can accelerate entry of potential allergens into the the tissues of the gut or airways. Moreover double stranded DNA (dsDNA) appears to act as a "danger signal", and as a Th2 adjuvant. cGAS, the molecule that detects cytosolic dsDNA, appears to be essential for the development and airway allergy. Therefore damage to epithelial barriers accompanied by cell death in the airways might cause infants to develop allergic responses to allergens that happen to be present at the same time as the exposure to bleach/detergent mixtures, or to other agents with similar properties.
Exposure of infants to such cleaning agents is likely to occur in homes of low SES where the mother may be cleaning while looking after infants, whereas in wealthy homes the cleaning is done by cleaning personnel, and the infant will not usually be present.
See additional explanations of this hypothesis on the cleaning_agent page.
This is clearly an important issue and there is urgent need for research to confirm or invalidate this hypothesis. It potentially explains why some workers find that domestic cleaning is associated with allergic disorders, while other authors do not.