Is there more direct evidence that organisms from the natural environment are
involved in control of the gut–brain axis? A recent study used a mouse model in
which a standardised stressor leads to colitis, behavioural changes (anxiety and fear)
and an altered microbiota. Pre-immunising these animals by the subcutaneous route
with a heat-killed soil-derived environmental saprophyte (Mycobacterium vaccae)
partially stabilised the microbiota, and eliminated the colitis and behavioural effects
(Reber et al. 2016). This protection was dependent on regulatory T cells (Treg)
(Reber et al. 2016), implying that contact with such soil organisms via cuts and
abrasions could affect mood. Another study exposed mice to very low doses of dust
from a soil with high microbial biodiversity, and saw changes in the gut microbiota,
and reduced anxiety, which they attributed to colonisation with a soil-derived
anaerobic spore-forming butyrate producer (Liddicoat et al. 2020).
Human epidemiological support comes from the observation that adults who
were brought up in an urban environment without pets had a greater inflammatory
response to a standard laboratory stressor (TSST) than did adults who had been
brought up on farms in the presence of animals (Bobel et al. 2018). Finally, there are
suggestive data from administration of probiotics to human subjects. While not
strictly environmental organisms, fermented foods are essentially metabolised by
organisms of environmental origin, such as our refrigerator-deprived ancestors
would have consumed. The subjects’ brains were monitored by functional magnetic
resonance imaging during exposure to an emotional stimulus, before and after
4 weeks consuming either a probiotic mixture, or a control material. The subjects
who had consumed the probiotic mixture showed significant changes in the activity
of brain regions that process emotion and sensation (Tillisch et al. 2013). This and
other experiments have inspired numerous clinical trials of probiotics as treatments
for psychiatric diseases. A recent meta-analysis of eligible studies (n ¼ 34) found
that the beneficial effects in depression are clearly significant (Liu et al. 2019).
18.4.12 Bacteriophages
Bacteriophages provide another possible mechanism that would enable the microbial
environment to modulate the microbiota and therefore immunoregulation. Phages
are the most numerous biological entities in the gut and approximately 90% of the
human gut virome consists of virulent bacteriophages predicted to target major
taxonomic groups of gut bacteria (Shkoporov et al. 2019). Some phages (lytic)
lyse the bacteria or archaea that they infect, while others (temperate phages) can
either trigger lysis, or alternatively, integrate into the host DNA or persist within the
host as a plasmid. Either way the phage exerts profound effects on the function and
survival of the host organisms. Integrated prophages can express genes that increase
the fitness of the bacteria and protect them from infection by lytic phages. They may
also supply bacteria with genes that are involved in the metabolism of toxins and
polysaccharides, or in antibiotic resistance. Some phages cause changes in the
350
G. A. W. Rook
involved in control of the gut–brain axis? A recent study used a mouse model in
which a standardised stressor leads to colitis, behavioural changes (anxiety and fear)
and an altered microbiota. Pre-immunising these animals by the subcutaneous route
with a heat-killed soil-derived environmental saprophyte (Mycobacterium vaccae)
partially stabilised the microbiota, and eliminated the colitis and behavioural effects
(Reber et al. 2016). This protection was dependent on regulatory T cells (Treg)
(Reber et al. 2016), implying that contact with such soil organisms via cuts and
abrasions could affect mood. Another study exposed mice to very low doses of dust
from a soil with high microbial biodiversity, and saw changes in the gut microbiota,
and reduced anxiety, which they attributed to colonisation with a soil-derived
anaerobic spore-forming butyrate producer (Liddicoat et al. 2020).
Human epidemiological support comes from the observation that adults who
were brought up in an urban environment without pets had a greater inflammatory
response to a standard laboratory stressor (TSST) than did adults who had been
brought up on farms in the presence of animals (Bobel et al. 2018). Finally, there are
suggestive data from administration of probiotics to human subjects. While not
strictly environmental organisms, fermented foods are essentially metabolised by
organisms of environmental origin, such as our refrigerator-deprived ancestors
would have consumed. The subjects’ brains were monitored by functional magnetic
resonance imaging during exposure to an emotional stimulus, before and after
4 weeks consuming either a probiotic mixture, or a control material. The subjects
who had consumed the probiotic mixture showed significant changes in the activity
of brain regions that process emotion and sensation (Tillisch et al. 2013). This and
other experiments have inspired numerous clinical trials of probiotics as treatments
for psychiatric diseases. A recent meta-analysis of eligible studies (n ¼ 34) found
that the beneficial effects in depression are clearly significant (Liu et al. 2019).
18.4.12 Bacteriophages
Bacteriophages provide another possible mechanism that would enable the microbial
environment to modulate the microbiota and therefore immunoregulation. Phages
are the most numerous biological entities in the gut and approximately 90% of the
human gut virome consists of virulent bacteriophages predicted to target major
taxonomic groups of gut bacteria (Shkoporov et al. 2019). Some phages (lytic)
lyse the bacteria or archaea that they infect, while others (temperate phages) can
either trigger lysis, or alternatively, integrate into the host DNA or persist within the
host as a plasmid. Either way the phage exerts profound effects on the function and
survival of the host organisms. Integrated prophages can express genes that increase
the fitness of the bacteria and protect them from infection by lytic phages. They may
also supply bacteria with genes that are involved in the metabolism of toxins and
polysaccharides, or in antibiotic resistance. Some phages cause changes in the
350
G. A. W. Rook