Sterile gut leads to lower anxiety, serotonin , and TPH-levels + some bacteria don't increase serotonin

Mauritio

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This study says:
Beyond the gut, germ free mice also display an increased turnover rate of dopamine and norepinephrine (as well as serotonin) in the brain (Diaz Heijtz et al., 2011), which could generally reduce pools in systemic circulation independent of microbial production (although factors influencing that increased turnover rate remain to be determined). " (1)



This study refers to another one, that mentions that germ free mice experience less anxiety and more activity in general:

"Using measures of motor activity and anxiety-like behavior, we demonstrate that germ free (GF) mice display increased motor activity and reduced anxiety, compared with specific pathogen free (SPF) mice with a normal gut microbiota. " (2)

The first study only looked at the brain turnover of the monoamines, whereas this study looked at various serotonin values in different places in the body.
Germ free mice had lower serotonin values in the colon, large intestine platelet rich plasma and fecal matter ,while also showing lower TPH( tryptophan hydroplase) activity!
Plus the activity of the of the serotonin transporter was increased 1,75 fold .
For some reason they showed higher 5ht levels in the small intestines. (3):
"Consistent with the understanding that much of the body’s 5-HT derives from the GI tract, we find that GF mice exhibit significantly decreased levels of colonic and fecal 5-HT compared to SPF controls (Figures 1B and S1A, and Table S1). This deficit in 5-HT is observed broadly across the distal, medial and proximal colon (Figure S1D), but not in the small intestine (Figures S1A, S2A and S2B), suggesting a specific role for the microbiota in regulating colonic 5-HT."

"GF mice also display elevated colonic expression of the 5-HT transporter SLC6A4"


They also show that germ free mice excrete higher amounts of tryptophan,possibly resulting from less conversion to serotonin:
".. GF mice exhibit significantly increased levels of the Tph substrate, tryptophan (Trp), in both feces (Table S1) and serum..."


Next they mention that theres actually a subsetof bacteria that does not produce or increase the serotonin levels of mice:
"Mice monocolonized with Bacteroides fragilis or Segmented Filamentous Bacteria (SFB) display deficits in serum 5-HT that are comparable to those seen in GF mice (Figure 3A). Moreover, postnatal colonization (P42) with Bacteroides uniformis, altered Schaedler flora (ASF), an eight-microbe consortium known to correct gross intestinal pathology in GF mice (Dewhirst et al., 1999), or with cultured Bacteroides spp. from the SPF mouse microbiota, has no significant effect on the 5-HT deficiency seen in GF mice (Figures 3A and 3B)."

They also found out that inhibiting TPH TPH decreases serotonin ,although there was a compensatory increase in TPH and decrease in serotonin transporter by the body. So even with a TPH-inhibitot you might not fully get rid of serotonin as the body adapts to it:
"Interestingly, inhibiting Tph activity with PCPA results in a compensatory increase in colonic TPH1 and decrease in SLC6A4 (Figures 3D and S2D)"
 

Mauritio

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One of the bacteria that dont produce higher serotonin levels, B. fragilis. , actually doesnt produce a "complete" endotoxin ,so I guess it might not lead to an activation of TLR4 and serotonin increase .
Kasper, Dennis L. "Surface antigens as virulence factors in infection with Bacteroides fragilis." Reviews of infectious diseases (1979)

Apprently it also produces succinate ,which has many benefits .
(Succinic acid production by Bacteroides fragilis. A potential bacterial virulence factor - PubMed)


Not only that, but it also seems to be low in people with autism and help autism related behaviour :
"Returning to mice, a third study - at the California Institute of Technology - focused on a microbe called Bacteroides fragilis, an absence of which is often observed in the guts of people with autism.

By transplanting B. fragilis from human donors into the guts of mice with symptoms similar to autism, they found the rodents exhibited less anxiety-like behavior, interacted more with other mice, and also behaved less repetitively."
Post in thread 'Why Is There So Much Soluble Fibre In Human Breast Milk?' Why Is There So Much Soluble Fibre In Human Breast Milk?
 

Mauritio

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B. fragilis might be worth a try. It is safe...
"In vivo safety was proven in both normal and immune-deficient mice." (1)

...and effective:
"They show that microbial shifts within the gut of a mouse resulted in changes of metabolites in the bloodstream and that these lead to the onset of autism-like behaviors. Moreover, administering a probiotic beneficial bacterium, Bacteroides fragilis, reversed the physiological, neurological and immunological anomalies."

"In offspring with reduced gut barrier integrity, the authors identified ~8% of assayed bacterial metabolites that differed significantly in abundance compared to those with intact gut barrier function. When these ASD mice were fed with Bacteroides fragilis, a gut microbe with positive effects on the immune system, the abundance of 34% of these metabolites changed back, gut barrier integrity was improved, the gut-microbiome was restored to a non-ASD state, and ASD-related behavioral abnormalities were ameliorated. In addition, a 46-fold increase of 4-ethylphenylsulfate (4-EPS) in the serum of MIA offspring returned to normal levels."

"A second metabolite elevated in the MIA serum, and normalized by treatment with B. fragilis, was indolepyruvate. Indolepyruvate is generated by microbial tryptophan catabolism and is related to indolyl-3-acryloylglycine, another human autism marker. Indolepyruvate elevation could be linked to increased serum levels of serotonin, yet another human autism biomarker. Application of the B. fragilis probiotic, increased many other metabolites including N-acetylserine, which the authors hypothesize may provide protection against some ASD symptoms." (2)

This suggests that it doesn't have a pro-serotonin effect as most bacteria have ,but might actually have anti-serotonin properties.
 

Mauritio

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Mauritio

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Weatuer it's harmful or beneficial Apparently seems to depend on which strain of B. fragilis is being used:

"Previous studies have identified B. fragilis as a common opportunistic pathogen in clinical infections and suggested that it may be responsible for a range of diseases involving a permeable intestinal barrier. However, recent studies of the relationship between nontoxigenic B. fragilis and the immune system have indicated that several B. fragilis strains may be potential probiotic."
 
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