ビフィズス菌の棲息環境による特性の違いおよび個別の菌株の生理作用に関する研究
概要
༤ኈㄽᩥ
ࣅࣇࢬࢫ⳦ࡢ᳇ᜥ⎔ቃࡼࡿ≉ᛶࡢ㐪࠸࠾ࡼࡧ
ಶูࡢ⳦ᰴࡢ⏕⌮స⏝㛵ࡍࡿ◊✲
௧ 2 ᖺ 6 ᭶
༡ ῟୍
┠ḟ
␎グ
➨㸯❶ ᗎㄽ
1.1. ⭠ෆ⣽⳦ྀᗣ ................................................................................................................. 3
1.2. ࣅࣇࢬࢫ⳦ࡢ✀㢮᳇ᜥ⎔ቃ ......................................................................................... 3
1.3. ⭠ෆ⣽⳦⫧‶ ..................................................................................................................... 4
1.4. ᮏ◊✲ࡢ┠ⓗ ......................................................................................................................... 6
➨㸰❶
ẕங୰ࡢࣅࣇࢬࢫ⳦㑅ᢥᅉᏊ㛵ࡍࡿ◊✲
2.1㸬ࡣࡌࡵ.................................................................................................................................. 9
2.2㸬᪉ἲ........................................................................................................................................ 10
ᚤ⏕≀⳦ᰴ
ẕங୰࠾ࡅࡿࣅࣇࢬࢫ⳦ࡢ⏕⫱ࡢホ౯
ࣜࢰࢳ࣮࣒ᑐࡍࡿ⪏ᛶࡢホ౯
2.3. ⤖ᯝ......................................................................................................................................... 12
ẕங୰࠾ࡅࡿࣅࣇࢬࢫ⳦ࡢ⏕⫱
ᰤ㣴⣲ࢆῧຍࡋࡓẕங୰࠾ࡅࡿࣅࣇࢬࢫ⳦ࡢ⏕⫱
ࣜࢰࢳ࣮࣒⪏ᛶ
2.4. ⪃ᐹ....................................................................................................................................... 14
➨㸱❶
ࣅࣇࢬࢫ⳦ % ࡢᦤྲྀࡀ⫧‶Ẽࡢᡂே࡛௦ㅰᶵ⬟ཬࡰࡍᙳ㡪
㛵ࡍࡿ⮫ᗋ◊✲
3.1. ࡣࡌࡵ............................................................................................................................... 18
3.2. ᪉ἲ....................................................................................................................................... 19
ヨ㦂ࢹࢨࣥ
ཧຍ⪅
ヨ㦂ᡭ㡰
ヨ㦂㣗ရ
ホ౯㡯┠
⤫ィゎᯒ
3.3. ⤖ᯝ....................................................................................................................................... 21
ཧຍ⪅ࡢ࣮࣋ࢫࣛࣥ≉ᛶ
య⤌ᡂࡢᙳ㡪
⾑ᾮ⤌ᡂᑐࡍࡿ %EUHYH% ࡢᙳ㡪
య⬡⫫㔞ࡢኚ⾑ᾮ⤌ᡂࡢ┦㛵
3.4㸬 ⪃ᐹ...................................................................................................................................... 22
➨㸲❶
%0, ࡀ㧗ࡵࡢᖖᡂேࢆᑐ㇟ࡋࡓࣅࣇࢬࢫ⳦ % ࡢయ⬡⫫పῶస
⏝㛵ࡍࡿ⮫ᗋ◊✲
4.1. ࡣࡌࡵ............................................................................................................................... 32
4.2. ᪉ἲ....................................................................................................................................... 32
ཧຍ⪅
ヨ㦂᪉ἲ
ヨ㦂㣗ရ
య⤌ᡂ ᐃ
⾑ᾮ᳨ᰝ࣭ᒀ᳨ᰝ
㣗ㄪᰝ
⤫ィゎᯒ
4.3. ⤖ᯝ....................................................................................................................................... 35
ཧຍ⪅ࡢ⫼ᬒ≉ᛶ㣗ㄪᰝ⤖ᯝ
య⤌ᡂ
᭷ຠᛶ㛵ࡍࡿ⾑ᾮࣃ࣓࣮ࣛࢱ
Ᏻᛶホ౯㛵ࡍࡿ⾑ᾮ࣭ᒀ᳨ᰝ
4.4. ⪃ᐹ....................................................................................................................................... 37
➨㸳❶
ᮏ◊✲ࡢ⥲ᣓ
5.1. ࣄࢺᖖᅾᛶࣅࣇࢬࢫ⳦ࡢẕஙぶᛶࡘ࠸࡚ ........................................................... 48
5.2. HRB ࡢࣜࢰࢳ࣮࣒⪏ᛶᶵᗎࡘ࠸࡚.............................................................................. 48
5.3. ࣅࣇࢬࢫ⳦ B-3 ࡢయ⬡⫫పῶస⏝ᶵᗎࡘ࠸࡚ ....................................................... 49
5.4. ᚋࡢㄢ㢟........................................................................................................................... 51
ཧ⪃ᩥ⊩
ㅰ㎡
␎グ
ALT; alanine transaminase
ALP; alkaline phosphatase
ANCOVA; analysis of co-variance
AST; aspartate transaminase
ATCC; American Type Culture Collection
B.; Bifidobacterium
BIA; Bioelectrical Impedance Analysis
BMI; Body Mass Index
CFU; colony forming unit
DSMZ; German Collection of Microorganisms (Deutsche Sammlung von Mikroorganismen und
Zellkulturen)
FGF; fibroblast growth factors
FXR; farnesoid X receptor
GLNBP; 1,3-E-galactosyl-N-acetylhexosamine phosphorylase
J-GTP; gamma-glutamyl transpeptidase
HbA1c; Hemoglobin A1c
hCRP; high-sensitivity C-reactive protein
HMOs; Human Milk Oligosaccharides
HRB; Human-Residential Bifidobacteria
JCM; Japan Collection of Microorganisms
L.; Lactobacillus
1
LBP; LPS-binding protein
LNB; Lact-N-biose
LPS; Lipopolysaccharide
MCC; Morinaga Culture Collection
MRS; de Man, Rogosa, and Sharpe Agar
TPY; Trypticase phytone yeast extract
2
➨㸯❶ ᗎㄽ
1.1. ⭠ෆ⣽⳦ྀᗣ
ࣄࢺࡢ⭠ෆࡣᩘⓒ✀㢮ࠊⓒಶ௨ୖࡢ⣽⳦ࡀ᳇ᜥࡋ࡚࠾ࡾࠊ⭠ෆ⣽⳦ྀࡋ࡚
ࣄࢺࡢᗣᐦ᥋㛵ࢃࡗ࡚࠸ࡿࡇࡀ᫂ࡽ࡞ࡗ࡚ࡁ࡚࠸ࡿࠋ㏆ᖺࡢከࡃࡢ◊✲ࡽࠊ
⭠ෆ⣽⳦ࡣࠊ⭠ࡀࢇࡸ⅖ᛶ⭠ᝈ࡞ࡢᾘ⟶ᝈࡔࡅ࡛࡞ࡃࠊ㠀ࣝࢥ࣮ࣝᛶ⬡⫫
ᛶ⫢⅖ࡸ 2 ᆺ⢾ᒀࠊ⫧‶࡞ࡢ㌟ᛶࡢ௦ㅰᝈࠊࡉࡽࡣㄆ▱ࡸ⮬㛢࡞ࡢ⢭⚄
ᝈࡶ㛵㐃ࡀ࠶ࡿࡇࡀ᫂ࡽ࡞ࡗ࡚ࡁ࡚࠸ࡿ 1)ࠋ
⭠ෆ⣽⳦ࡢ୰࡛ࣅࣇࢬࢫ⳦ࡣஙඣ࠾ࡼࡧᡂே࠾࠸࡚᭱ඃໃ⳦✀ࡢࡦࡘ࡛
࠶ࡿ 2)ࠋ≉㞳ங๓ࡢஙඣ⭠⟶ෆࡣࣅࣇࢬࢫ⳦ࡀ㠀ᖖ㧗࠸ྜ࡛᳇ᜥࡋ࡚࠾ࡾࠊᮍ
⇍࡞ஙᗂඣࢆᏲࡿࡃ⭠ෆࡢ⎔ቃ⥔ᣢ㈉⊩ࡋ࡚࠸ࡿ⪃࠼ࡽࢀ࡚࠸ࡿ 3)ࠋࣅࣇࢬࢫ⳦
ࡢࣄࢺࡢ⏕⌮స⏝ࡘ࠸࡚ࡣࠊᩚ⭠స⏝ࢆࡣࡌࡵࡋ࡚චㄪ⠇స⏝ࡸࠊࣞࣝࢠ࣮ᢚ
ไస⏝ࠊឤᰁ㜵ᚚస⏝ࠊᢠ⫧‶స⏝࡞ᩘከࡃࡢሗ࿌ࡀ࠶ࡾ 4) 㸦Fig. 1-1㸧ࠊࣉࣟࣂ࢜ࢸ
ࢡࢫࡢ௦⾲ࡋ࡚Ⓨ㓝ங〇ရࡸࢧࣉ࣓ࣜࣥࢺࠊ⫱ඣ⢊ங࡞ᖜᗈࡃ⏝ࡉࢀ࡚࠸ࡿࠋ
1.2. ࣅࣇࢬࢫ⳦ࡢ✀㢮᳇ᜥ⎔ቃ
ࣅࣇࢬࢫ⳦ࡣࠊActinobacteria 㛛 Bifidobacterium ᒓᒓࡍࡿ⣽⳦ࢆᣦࡋࠊ2020
ᖺ 1 ᭶⌧ᅾ 69 ✀ࠊ10 ள✀ࢆྵࡴ 79 ࡢ✀㢮ࡀྠᐃࡉࢀ࡚࠸ࡿ 5)ࠋ⮬↛⏺࠾࠸࡚ࣅࣇࢬ
ࢫ⳦ࡢ᳇ᜥሙᡤࡣࠊࣄࢺࡸࡑࡢ့ங㢮ࠊ㫽㢮ࠊ᪻ࡢ⭠⟶࡞ࡀᣲࡆࡽࢀࠊ✀࣭ள✀
ࡼࡗ࡚᳇ᜥሙᡤࡣ␗࡞ࡿࠋࣄࢺ⭠⟶ࡽ᳨ฟࡉࢀࡿࣅࣇࢬࢫ⳦ࡣ 10 ⳦✀⛬ᗘ࡛࠶
ࡾ 6–8)ࠊࡇࢀࡽࡣࣄࢺᖖᅾᛶࣅࣇࢬࢫ⳦㸦Human-Residential Bifidobacteria; HRB㸧ࡤ
ࢀ 9,10)ࠊࣄࢺ௨እࡽ᳨ฟࡉࢀࡿࣅࣇࢬࢫ⳦㸦Non-HRB㸧ࡢ⳦✀᫂☜༊ูࡍࡿࡇ
ࡀ࡛ࡁࡿࠋࡉࡽࠊஙඣᡂே࡛ࡶ᳇ᜥࡍࡿ⳦✀ࡀ␗࡞ࡗ࡚࠾ࡾࠊஙඣࡢ⭠⟶ ࡣ
Bifidobacterium longum (subsp. longum ࠾ࡼࡧ infantis)ࠊB. breveࠊB. bifidum ࠸ࡗࡓ⳦✀࣭
ள✀㸦ஙඣᆺ HRB㸧ࡀඃໃᐃ╔ࡋ࡚࠾ࡾ 11,12)ࠊᡂேࡢ⭠⟶ࡣ B. longum subsp. longum
3
ࡢࠊB. adlescentisࠊB. pseudocatenulatum ࠸ࡗࡓ⳦✀㸦ᡂேᆺ HRB㸧ࡀ᳇ࢇ࡛࠸ࡿ 13)ࠋ
⯆῝࠸ࡇࠊ၏୍ B. longum subsp. longum ࡣஙඣࡽᡂேࡲ࡛ᖜᗈ࠸ᖺ㱋ᒙ᳨࡛ฟࡉ
ࠋ
ࢀࡿ 2,14)㸦Fig. 1-2㸧
⭠ෆ⣽⳦◊✲࠾࠸࡚ࠕ࡞ࡐࣄࢺࡣ≉ᐃࡢࣅࣇࢬࢫ⳦⳦✀ࡀ᳇ᜥࡋ࡚࠸ࡿࡢ
ࠖ࠸࠺㢟ࡀ࠶ࡾࠊࡑࡢゎ᫂ྥࡅ࡚ࠊHRB Non-HRB ╔┠ࡋࡓ◊✲ࡀሗ࿌ࡉࢀ
࡚࠸ࡿࠋࣉࣟࣂ࢜ࢸࢡࢫࡋ࡚ᖜᗈࡃ⏝ࡉࢀ࡚࠸ࡿ 3 ⳦✀ࠊࡍ࡞ࢃࡕஙඣᆺ HRB
࡛࠶ࡿ B. longum (subsp. longum ࠾ࡼࡧ infantis) B. breveࠊ࠾ࡼࡧ Non-HRB ࡛࠶ࡿ B.
animalis㸦subsp. animalis ࠾ࡼࡧ lactis㸧ࡽィ 49 ⳦ᰴࢆᑐ㇟ẚ㍑ࢤࣀ࣒ゎᯒࢆ⾜ࡗࡓ◊
✲࡛ࡣࠊஙඣᆺ HRB Non-HRB ࡢ㛫ࡣಖ᭷ࡍࡿⅣỈ≀௦ㅰ㛵㐃㑇ఏᏊࡁ࡞
㐪 ࠸ ࡀ ࠶ ࡿ ࡇ ࠊ ๓ ⪅ ࡣ ẕ ங ྵ ࡲ ࢀ ࡿ ࣄ ࢺ ࣑ ࣝ ࢡ ࢜ ࣜ ࢦ ⢾ 㸦 Human Milk
Oligosaccharides, HMOs㸧ࡢ௦ㅰ㛵㐃㑇ఏᏊࡀከࡃศᕸࡋ࡚࠸ࡿࡇࡀ♧ࡉࢀ࡚࠸ࡿ 9)ࠋࡲ
ࡓ 0 ᡯࡽ 98 ṓࡢᗣ࡞᪥ᮏே࡞ࡽ༢㞳ࡋࡓ 145 ᰴࡢ B. longum subsp. longum ࡘ
࠸࡚ಖ᭷ࡋ࡚࠸ࡿ㑇ఏᏊሗࡢከᵝᛶศᕸࢆㄪࡓ⤖ᯝࠊB. longum subsp. longum ࡣࠊ
ஙඣ⭠⟶࡛ࡢ⏕⫱᭷࡞ࢩࣝ㓟௦ㅰ㛵ࢃࡿ㑇ఏᏊຍ࠼ࠊ⡿ࡸᑠ㯏࡞ࡢ✐≀ྵ
ࡲࢀࡿ⧄⥔㉁ࡸ⢾ࢱࣥࣃࢡࢆ⏝ࡍࡿࡓࡵࡢ㑇ఏᏊࢆಖ᭷ࡋ࡚࠸ࡿ⳦ᰴࡶᏑᅾࡋ࡚࠸ࡿ
ࡇࡽࠊࡇࡢ✀ࡔࡅࡀᡂேࡸ㧗㱋⪅ࡲ࡛ᖜᗈ࠸ᖺ௦࡛⭠⟶᳇ᜥࡋ࡚࠸ࡿ⌮⏤ࡢ୍➃ࡀ
♧ࡉࢀ࡚࠸ࡿ 15,16)ࠋࡇࡢࡼ࠺ࠊࣅࣇࢬࢫ⳦ࡣ᳇ᜥࡍࡿ⎔ቃྜࢃࡏ࡚ྛ⳦✀㐺ᛂ㐍
ࡋࡓ⪃࠼ࡽࢀࡿࡀࠊ࡞ࡐࣄࢺࡣ≉ᐃࡢࣅࣇࢬࢫ⳦⳦✀ࡀ᳇ᜥࡋ࡚࠸ࡿࡢࠊࡑࡢ
࣓࢝ࢽࢬ࣒ࡣᮍࡔᮍゎ᫂࡞Ⅼࡀከࡃṧࡉࢀ࡚࠸ࡿࠋ
1.3. ...