US 11,655,493 B2
Biomarker for mental disease
Hiroshi Kunugi, Kodaira (JP); Emiko Aizawa, Kodaira (JP); and Hirokazu Tsuji, Funabashi (JP)
Assigned to NATIONAL CENTER OF NEUROLOGY AND PSYCHIATRY, Kodaira (JP); and KABUSHIKI KAISHA YAKULT HONSHA, Tokyo (JP)
Appl. No. 15/566,290
Filed by NATIONAL CENTER OF NEUROLOGY AND PSYCHIATRY, Kodaira (JP); and KABUSHIKI KAISHA YAKULT HONSHA, Tokyo (JP)
PCT Filed Apr. 15, 2016, PCT No. PCT/JP2016/062182
§ 371(c)(1), (2) Date Oct. 13, 2017,
PCT Pub. No. WO2016/167365, PCT Pub. Date Oct. 20, 2016.
Claims priority of application No. JP2015-083936 (JP), filed on Apr. 16, 2015.
Prior Publication US 2018/0100177 A1, Apr. 12, 2018
Int. Cl. C12Q 1/06 (2006.01); A61K 45/00 (2006.01); G01N 33/569 (2006.01); C12Q 1/689 (2018.01); C12Q 1/6883 (2018.01); G01N 33/15 (2006.01); C12Q 1/10 (2006.01); C12Q 1/14 (2006.01); G01N 33/487 (2006.01); C12N 1/20 (2006.01); C12Q 1/68 (2018.01)
CPC C12Q 1/06 (2013.01) [A61K 45/00 (2013.01); C12Q 1/10 (2013.01); C12Q 1/14 (2013.01); C12Q 1/689 (2013.01); C12Q 1/6883 (2013.01); G01N 33/15 (2013.01); G01N 33/48735 (2013.01); G01N 33/56911 (2013.01); G01N 33/56916 (2013.01); C12N 1/20 (2013.01); C12Q 1/68 (2013.01); G01N 2800/065 (2013.01); G01N 2800/302 (2013.01); G01N 2800/304 (2013.01)] 5 Claims
 
1. A method of identifying an agent as highly likely being a mental disease-improving agent, the method comprising:
administering a test substance to a subject,
obtaining a fecal specimen from the subject and a fecal specimen from a subject that has not been administered the test substance,
conducting RNA extraction from the fecal specimens,
measuring the number of enterobacterial cells contained in the fecal specimens by subjecting the extracted RNA to RT-PCR using primers,
comparing the number of enterobacterial cells contained in the fecal specimen of the subject and the number of enterobacterial cells contained in the fecal specimen of the unadministered subject, and
identifying the test substance as an agent which is highly likely a mental disease-improving agent when the test substance has increased the number of the enterobacterial cells, has promoted an increase in the number of the enterobacterial cells, or has suppressed a decrease in the number of the enterobacterial cells in the administered subject compared to the unadministered subject,
wherein the subject is a human, a mouse, a rat, or a rabbit, and
wherein when the mental disease is depression, the enterobacterial cells are cells of Bifidobacterium and/or Lactobacillus,
wherein when the mental disease is manic depression, the enterobacterial cells are cells of Staphylococcus, or
wherein when the mental disease is schizophrenia, the enterobacterial cells are cells of Lactobacillus sakei subgroup and/or Bacteroides fragilis group,
wherein feces obtained from the following subjects are excluded:
males and females older than or equal to 63 years;
patients with complications of severe medical diseases;
patients taking antibiotics;
patients having intellectual disability, epilepsy, or severe congenital abnormality;
patients with surgical history of intestinal tract;
wherein exclusion criteria minimize the influence of aging, health issues other than a mental disease, and agents that affect the survivability of enterobacteria, wherein a difference in the numbers of the enterobacterial cells between the subject that has been administered the test substance and the unadministered subject identifies the test substance as highly likely being a mental disease-improving agent.