Title:  Administering bacteria to improve sleep

United States Patent:  6,444,203

Issued:  September 3, 2002

Inventors:  Krueger; James M. (Pullman, WA); Pabst; Michael J. (Germantown, TN); Cayuela; Chantal (Paris, FR); Degivry; Marie-Christine (Le Plessis-Robinson, FR); Hartley; Donna (Arlington, TX)

Assignee:  Compagnie Gervais Danone (Paris, FR)

Appl. No.:  466768

Filed:  December 20, 1999

A method of improving sleep in a mammal having a sleep disorder is disclosed. The method includes identifying the mammal having a sleep disorder and then administering Lactobacillus acidophilus CNCM I-2274, Lactobacillus acidophilus CNCM I-2132, Lactobacillus helveticus CNCM I-2275, Streptococcus thermophilus CNCM I-1520, Streptococcus thermophilus CNCM I-2272 or mixtures thereof. The method increases the length of the non rapid eye movement sleep phase and decreases the length of the rapid eye movement sleep phase. The bacteria can be administered in an orally consumable food product or a dietary supplement.

SUMMARY OF THE INVENTION

The inventors have found that non-pathogenic bacteria that do not cause an infection, such as lactic acid bacteria, can modify the phases of sleep, for example, can increase the length of NREM deep sleep. They noted that the lactic acid bacteria that lead to an increase the NREM phase are those whose cell wall is sensitive to the action of muramidase-type enzymes, such as lysozyme or mutanolysin.

The inventors studied the action of a muramidase, mutanolysin, on the cell walls of different lactic acid bacteria, in particular on the cell walls of Lactobacillus gasseri 9221 (CNCM I-2131), Lactobacillus acidophilus 9223 (CNCM I-2274), Lactobacillus acidophilus 9173 (CNCM I-2132), Lactobacillus helveticus 9343 (CNCM I-2275), Streptococcus thermophilus 9340 (CNCM I-1520) and Streptococcus thermophilus 10090 (CNCM I-2272). They noted that the cell walls of Lactobacillus acidophilus 9223 (CNCM I-2274), Lactobacillus acidophilus 9173 (CNCM I-2132), Lactobacillus helveticus 9343 (CNCM I-2275), Streptococcus thermophilus 9340 (CNCM I-1520) and Streptococcus thermophilus 10090 (CNCM I-2272) were hydrolyzed by the mutanolysin, yielding two fractions: a soluble fraction containing muramylpeptides and an insoluble fraction. In contrast, the cell walls of Lactobacillus gasseri 9221 (CNCM I-2131) were not hydrolyzed by mutanolysin, and muramylpeptides were not liberated. After incubating Lactobacillus gasseri 9221 (CNCM I-2131, deposited on Feb. 24, 1999) with mutanolysin, only the insoluble fraction could be recovered.

The effects of the lactic acid bacteria whose cell walls are hydrolyzed by muramidase-type enzymes on sleep has been validated by studying two experimental systems:

1) In vitro experiments with human monocytes showed that the lactic acid bacteria whose cell walls are hydrolyzed by mutanolysin to give a soluble fraction containing muramylpeptides were capable of strongly activating the monocytes, inducing increased production of superoxide anion, and also inducing production of the cytokines IL-1.beta. and TNF.alpha.. Superoxide anion is an oxygen radical produced by monocytes that is directly involved in the killing of microbes. The cytokines are a family of protein inflammatory mediators that are known to be involved in the regulation of sleep. These monocyte activation effects were observed with both Lactobacillus and Streptococcus, including Lactobacillus acidophilus 9223, Lactobacillus acidophilus 9173, Lactobacillus helveticus 9343, Streptococcus thermophilus 9340 and Streptococcus thermophilus 10090.

2) In vivo experiments in rabbits showed that lactic acid bacteria whose cell wall is hydrolyzed by mutanolysin to give a soluble fraction containing muramylpeptides influenced the phases of sleep. Sleep was analyzed by electroencephalograms (EEG). Notably, such muramylpeptides increased the phase of sleep called NREM (Non Rapid Eye Movement) and decreased the phase of sleep called REM (Rapid Eye Movement).

The present invention describes several bacteria that improve the quality of sleep by increasing the length of the Non Rapid Eye Movement (NREM) sleep phase. Other important characteristics of the bacteria are that they are non-pathogenic for humans, and that their cell walls are sensitive to the action of muramidase-type enzymes, in particular to the action of mutanolysin.

Claim 1 of 7 Claims

What is claimed is:

1. A method of improving sleep in a mammal having a sleep disorder comprising the steps of:

identifying a mammal with said sleep disorder; and

administering a bacteria selected from the group consisting of Lactobacillus acidophilus CNCM I-2274, Lactobacillus acidophilus CNCM I-2132, Lactobacillus helveticus CNCM I-2275, Streptococcus thermophilus CNCM I-1520, Streptococcus thermophilus CNCM I-2272, and mixtures thereof;

wherein length of non rapid eye movement sleep phase is increased or length of rapid eye movement sleep phase is decreased in said mammal.
 

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