GABA Modulating Bacteria of the Human Gut Microbiome

[h3ro]

Authors
P. Strandwitz1, K. Kim2, D. Dietrich2, D. McDonald3, T. Ramadhar2, E. J. Stewart1, R. Knight3, J. Clardy2, K. Lewis1; 1Northeastern Univ., Boston, MA, 2Harvard Med. Sch., Boston, MA, 3Univ. of California, San Diego, La Jolla, CA

Disclosures
P. Strandwitz: None. K. Kim: None. D. Dietrich: None. D. McDonald: None. T. Ramadhar: None. E.J. Stewart: None. R. Knight: None. J. Clardy: None. K. Lewis:None.

Abstract
The gut microbiome affects many different diseases, and has been recently linked to human mental health. The microbiome community is diverse, but 50-80% of its diversity remains uncultured. We previously reported that uncultured bacteria from the marine environment require growth factors from neighboring species, and by using co-culture, we could cultivate novel diversity. In the present study, we used a similar co-culture approach to grow bacteria from humans stool samples. KLE1738, a “Most-Wanted” member of the human gut microbiome only known by its 16S rDNA signature, was found to require the presence of Bacteroides fragilis KLE1758 for growth. Using bio-assay driven purification of B. fragilis KLE1758supernatant, γ-aminobutyric acid (GABA), the major inhibitory neurotransmitter of the central nervous system, was identified as the growth factor for KLE1738. We found no other tested compound but GABA supported the growth of KLE1738, and genomic analysis suggests an unusual metabolism focused on consuming GABA. Due to this unique growth requirement, we provisionally name KLE1738 Evtepia gabavorous. Using growth of E. gabalyticus as an indicator, we then identified novel GABA producing bacteria from the gut microbiome. Reduced levels of GABA are associated with depression, and we found fewer GABA producers in a human cohort of depressed individuals. By modulating the level of GABA, microbial producers and consumers of this neurotransmitter may be influencing host behavior.

http://www.abstractsonline.com/pp8/#!/4060/presentation/18619

 

[Cort]

Authors
P. Strandwitz1, K. Kim2, D. Dietrich2, D. McDonald3, T. Ramadhar2, E. J. Stewart1, R. Knight3, J. Clardy2, K. Lewis1; 1Northeastern Univ., Boston, MA, 2Harvard Med. Sch., Boston, MA, 3Univ. of California, San Diego, La Jolla, CA

Disclosures
P. Strandwitz: None. K. Kim: None. D. Dietrich: None. D. McDonald: None. T. Ramadhar: None. E.J. Stewart: None. R. Knight: None. J. Clardy: None. K. Lewis:None.

Abstract
The gut microbiome affects many different diseases, and has been recently linked to human mental health. The microbiome community is diverse, but 50-80% of its diversity remains uncultured. We previously reported that uncultured bacteria from the marine environment require growth factors from neighboring species, and by using co-culture, we could cultivate novel diversity. In the present study, we used a similar co-culture approach to grow bacteria from humans stool samples. KLE1738, a “Most-Wanted” member of the human gut microbiome only known by its 16S rDNA signature, was found to require the presence of Bacteroides fragilis KLE1758 for growth. Using bio-assay driven purification of B. fragilis KLE1758supernatant, γ-aminobutyric acid (GABA), the major inhibitory neurotransmitter of the central nervous system, was identified as the growth factor for KLE1738. We found no other tested compound but GABA supported the growth of KLE1738, and genomic analysis suggests an unusual metabolism focused on consuming GABA. Due to this unique growth requirement, we provisionally name KLE1738 Evtepia gabavorous. Using growth of E. gabalyticus as an indicator, we then identified novel GABA producing bacteria from the gut microbiome. Reduced levels of GABA are associated with depression, and we found fewer GABA producers in a human cohort of depressed individuals. By modulating the level of GABA, microbial producers and consumers of this neurotransmitter may be influencing host behavior.

http://www.abstractsonline.com/pp8/#!/4060/presentation/18619

Since a GABA/Glutamate imbalance is suspected in many diseases including FM and ME/CFS this could be big. Could low GABA be due to a deficiency of these bacteria? It's the serotonin - Mady Hornig has reported that a subset of ME/CFS patients tested in their gut study have low serotonin...

What a great way to increase these chemicals by adding probiotics to our guts! That would be huge......Hopefully that is in the future.

Not good to have low levels of these feel good chemicals!

Thanks for posting.

 

[Cort]

Since a GABA/Glutamate imbalance is suspected in many diseases including FM and ME/CFS this could be big. Could low GABA be due to a deficiency of these bacteria? It's the serotonin - Mady Hornig has reported that a subset of ME/CFS patients tested in their gut study have low serotonin...

What a great way to increase these chemicals by adding probiotics to our guts! That would be huge......Hopefully that is in the future.

Not good to have low levels of these feel good chemicals!

Thanks for posting.

Check out this 2015 finding - probiotics affect microglial activation in the brain.

http://www.ncbi.nlm.nih.gov/pubmed/26224864

Using a well characterized mouse model of liver inflammation, we now show that probiotic (VSL#3) treatment attenuates sickness behavior development in mice with liver inflammation without affecting disease severity, gut microbiota composition, or gut permeability. Attenuation of sickness behavior development was associated with reductions in microglial activation and cerebral monocyte infiltration. These events were paralleled by changes in markers of systemic immune activation, including decreased circulating TNF-α levels. Our observations highlight a novel pathway through which probiotics mediate cerebral changes and alter behavior. These findings allow for the potential development of novel therapeutic interventions targeted at the gut microbiome to treat inflammation-associated sickness behaviors in patients with systemic inflammatory diseases.