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

ࣅࣇ࢕ࢬࢫ⳦ࡢ᳇ᜥ⎔ቃ࡟ࡼࡿ≉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. ࣅࣇ࢕ࢬࢫ⳦ࡢ✀㢮࡜᳇ᜥ⎔ቃ ......................................................................................... 3
1.3. ⭠ෆ⣽⳦࡜⫧‶ ..................................................................................................................... 4
1.4. ᮏ◊✲ࡢ┠ⓗ ......................................................................................................................... 6

➨㸰❶

ẕங୰ࡢࣅࣇ࢕ࢬࢫ⳦㑅ᢥᅉᏊ࡟㛵ࡍࡿ◊✲

2.1㸬ࡣࡌࡵ࡟.................................................................................................................................. 9
2.2㸬᪉ἲ........................................................................................................................................ 10
  ᚤ⏕≀⳦ᰴ
  ẕங୰࡟࠾ࡅࡿࣅࣇ࢕ࢬࢫ⳦ࡢ⏕⫱ࡢホ౯
  ࣜࢰࢳ࣮࣒࡟ᑐࡍࡿ⪏ᛶࡢホ౯
2.3. ⤖ᯝ......................................................................................................................................... 12
  ẕங୰࡟࠾ࡅࡿࣅࣇ࢕ࢬࢫ⳦ࡢ⏕⫱
  ᰤ㣴⣲ࢆῧຍࡋࡓẕங୰࡟࠾ࡅࡿࣅࣇ࢕ࢬࢫ⳦ࡢ⏕⫱
  ࣜࢰࢳ࣮࣒⪏ᛶ
2.4. ⪃ᐹ....................................................................................................................................... 14

➨㸱❶

ࣅࣇ࢕ࢬࢫ⳦ % ࡢᦤྲྀࡀ⫧‶Ẽ࿡ࡢᡂே࡛௦ㅰᶵ⬟࡟ཬࡰࡍᙳ㡪࡟

㛵ࡍࡿ⮫ᗋ◊✲
3.1. ࡣࡌࡵ࡟............................................................................................................................... 18
3.2. ᪉ἲ....................................................................................................................................... 19

  ヨ㦂ࢹࢨ࢖ࣥ
  ཧຍ⪅
  ヨ㦂ᡭ㡰
  ヨ㦂㣗ရ
  ホ౯㡯┠
  ⤫ィゎᯒ
3.3. ⤖ᯝ....................................................................................................................................... 21
  ཧຍ⪅ࡢ࣮࣋ࢫࣛ࢖ࣥ≉ᛶ
  య⤌ᡂ࡬ࡢᙳ㡪
  ⾑ᾮ⤌ᡂ࡟ᑐࡍࡿ %EUHYH% ࡢᙳ㡪
  య⬡⫫㔞ࡢኚ໬࡜⾑ᾮ⤌ᡂࡢ┦㛵
3.4㸬 ⪃ᐹ...................................................................................................................................... 22

➨㸲❶

%0, ࡀ㧗ࡵࡢ೺ᖖᡂேࢆᑐ㇟࡜ࡋࡓࣅࣇ࢕ࢬࢫ⳦ % 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
  Ᏻ඲ᛶホ౯࡟㛵ࡍࡿ⾑ᾮ࣭ᒀ᳨ᰝ
4.4. ⪃ᐹ....................................................................................................................................... 37

➨㸳❶

ᮏ◊✲ࡢ⥲ᣓ

5.1. ࣄࢺᖖᅾᛶࣅࣇ࢕ࢬࢫ⳦ࡢẕஙぶ࿴ᛶ࡟ࡘ࠸࡚ ........................................................... 48
5.2. HRB ࡢࣜࢰࢳ࣮࣒⪏ᛶᶵᗎ࡟ࡘ࠸࡚.............................................................................. 48
5.3. ࣅࣇ࢕ࢬࢫ⳦ B-3 ࡢయ⬡⫫పῶస⏝ᶵᗎ࡟ࡘ࠸࡚ ....................................................... 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⭠ෆ࡟ࡣᩘⓒ✀㢮ࠊⓒ඙ಶ௨ୖࡢ⣽⳦ࡀ᳇ᜥࡋ࡚࠾ࡾࠊ⭠ෆ⣽⳦ྀ࡜ࡋ࡚
ࣄࢺࡢ೺ᗣ࡜ᐦ᥋࡟㛵ࢃࡗ࡚࠸ࡿࡇ࡜ࡀ᫂ࡽ࠿࡟࡞ࡗ࡚ࡁ࡚࠸ࡿࠋ㏆ᖺࡢከࡃࡢ◊✲࠿ࡽࠊ
⭠ෆ⣽⳦ࡣࠊ኱⭠ࡀࢇࡸ⅖⑕ᛶ⭠⑌ᝈ࡞࡝ࡢᾘ໬⟶⑌ᝈࡔࡅ࡛࡞ࡃࠊ㠀࢔ࣝࢥ࣮ࣝᛶ⬡⫫
ᛶ⫢⅖ࡸ 2 ᆺ⢾ᒀ⑓ࠊ⫧‶࡞࡝ࡢ඲㌟ᛶࡢ௦ㅰ⑌ᝈࠊࡉࡽ࡟ࡣㄆ▱⑕ࡸ⮬㛢⑕࡞࡝ࡢ⢭⚄
⑌ᝈ࡜ࡶ㛵㐃ࡀ࠶ࡿࡇ࡜ࡀ᫂ࡽ࠿࡟࡞ࡗ࡚ࡁ࡚࠸ࡿ 1)ࠋ
⭠ෆ⣽⳦ࡢ୰࡛ࣅࣇ࢕ࢬࢫ⳦ࡣஙඣ࠾ࡼࡧᡂே࡟࠾࠸࡚᭱ඃໃ⳦✀ࡢࡦ࡜ࡘ࡛
࠶ࡿ 2)ࠋ≉࡟㞳ங๓ࡢஙඣ⭠⟶ෆ࡟ࡣࣅࣇ࢕ࢬࢫ⳦ࡀ㠀ᖖ࡟㧗࠸๭ྜ࡛᳇ᜥࡋ࡚࠾ࡾࠊᮍ
⇍࡞ஙᗂඣࢆᏲࡿ࡭ࡃ⭠ෆࡢ⎔ቃ⥔ᣢ࡟㈉⊩ࡋ࡚࠸ࡿ࡜⪃࠼ࡽࢀ࡚࠸ࡿ 3)ࠋࣅࣇ࢕ࢬࢫ⳦
ࡢࣄࢺ࡬ࡢ⏕⌮స⏝࡟ࡘ࠸࡚ࡣࠊᩚ⭠స⏝ࢆࡣࡌࡵ࡜ࡋ࡚ච␿ㄪ⠇స⏝ࡸࠊ࢔ࣞࣝࢠ࣮ᢚ
ไస⏝ࠊឤᰁ㜵ᚚస⏝ࠊᢠ⫧‶స⏝࡞࡝ᩘከࡃࡢሗ࿌ࡀ࠶ࡾ 4) 㸦Fig. 1-1㸧ࠊࣉࣟࣂ࢖࢜ࢸ
࢕ࢡࢫࡢ௦⾲࡜ࡋ࡚Ⓨ㓝ங〇ရࡸࢧࣉ࣓ࣜࣥࢺࠊ⫱ඣ⢊ங࡞࡝࡟ᖜᗈࡃ฼⏝ࡉࢀ࡚࠸ࡿࠋ

1.2. ࣅࣇ࢕ࢬࢫ⳦ࡢ✀㢮࡜᳇ᜥ⎔ቃ
ࣅࣇ࢕ࢬࢫ⳦࡜ࡣࠊActinobacteria 㛛 Bifidobacterium ᒓ࡟ᒓࡍࡿ⣽⳦ࢆᣦࡋࠊ2020
ᖺ 1 ᭶⌧ᅾ 69 ✀ࠊ10 ள✀ࢆྵࡴ 79 ࡢ✀㢮ࡀྠᐃࡉࢀ࡚࠸ࡿ 5)ࠋ⮬↛⏺࡟࠾࠸࡚ࣅࣇ࢕ࢬ
ࢫ⳦ࡢ᳇ᜥሙᡤࡣࠊࣄࢺࡸࡑࡢ௚့ங㢮ࠊ㫽㢮ࠊ᪻⹸ࡢ⭠⟶࡞࡝ࡀᣲࡆࡽࢀࠊ✀࣭ள✀࡟
ࡼࡗ࡚᳇ᜥሙᡤࡣ␗࡞ࡿࠋ୺࡟ࣄࢺ⭠⟶࠿ࡽ᳨ฟࡉࢀࡿࣅࣇ࢕ࢬࢫ⳦ࡣ 10 ⳦✀⛬ᗘ࡛࠶
ࡾ 6–8)ࠊࡇࢀࡽࡣࣄࢺᖖᅾᛶࣅࣇ࢕ࢬࢫ⳦㸦Human-Residential Bifidobacteria; HRB㸧࡜࿧ࡤ
ࢀ 9,10)ࠊࣄࢺ௨እ࠿ࡽ᳨ฟࡉࢀࡿࣅࣇ࢕ࢬࢫ⳦㸦Non-HRB㸧ࡢ⳦✀࡜᫂☜࡟༊ูࡍࡿࡇ࡜
ࡀ࡛ࡁࡿࠋࡉࡽ࡟ࠊஙඣ࡜ᡂே࡛ࡶ᳇ᜥࡍࡿ⳦✀ࡀ␗࡞ࡗ࡚࠾ࡾࠊஙඣࡢ⭠⟶ ࡟ࡣ
Bifidobacterium longum (subsp. longum ࠾ࡼࡧ infantis)ࠊB. breveࠊB. bifidum ࡜࠸ࡗࡓ⳦✀࣭
ள✀㸦ஙඣᆺ HRB㸧ࡀඃໃ࡟ᐃ╔ࡋ࡚࠾ࡾ 11,12)ࠊᡂேࡢ⭠⟶࡟ࡣ B. longum subsp. longum

3

ࡢ௚ࠊB. adlescentisࠊB. pseudocatenulatum ࡜࠸ࡗࡓ⳦✀㸦ᡂேᆺ HRB㸧ࡀ᳇ࢇ࡛࠸ࡿ 13)ࠋ
⯆࿡῝࠸ࡇ࡜࡟ࠊ၏୍ B. longum subsp. longum ࡣஙඣ࠿ࡽᡂேࡲ࡛ᖜᗈ࠸ᖺ㱋ᒙ᳨࡛ฟࡉ
ࠋ
ࢀࡿ 2,14)㸦Fig. 1-2㸧
⭠ෆ⣽⳦◊✲࡟࠾࠸࡚ࠕ࡞ࡐࣄࢺ࡟ࡣ≉ᐃࡢࣅࣇ࢕ࢬࢫ⳦⳦✀ࡀ᳇ᜥࡋ࡚࠸ࡿࡢ
࠿ࠖ࡜࠸࠺࿨㢟ࡀ࠶ࡾࠊࡑࡢゎ᫂࡟ྥࡅ࡚ࠊHRB ࡜ Non-HRB ࡟╔┠ࡋࡓ◊✲ࡀሗ࿌ࡉࢀ
࡚࠸ࡿࠋࣉࣟࣂ࢖࢜ࢸ࢕ࢡࢫ࡜ࡋ࡚ᖜᗈࡃ฼⏝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ఏᏊ࡟኱ࡁ࡞
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࠸ࡿࡇ࡜ࡀ♧ࡉࢀ࡚࠸ࡿ 9)ࠋࡲ
ࡓ 0 ᡯ࠿ࡽ 98 ṓࡢ೺ᗣ࡞᪥ᮏே࡞࡝࠿ࡽ༢㞳ࡋࡓ 145 ᰴࡢ B. longum subsp. longum ࡟ࡘ
࠸࡚ಖ᭷ࡋ࡚࠸ࡿ㑇ఏᏊ᝟ሗࡢከᵝᛶ࡜ศᕸࢆㄪ࡭ࡓ⤖ᯝࠊB. longum subsp. longum ࡣࠊ
ஙඣ⭠⟶࡛ࡢ⏕⫱࡟᭷฼࡞ࢩ࢔ࣝ㓟௦ㅰ࡟㛵ࢃࡿ㑇ఏᏊ࡟ຍ࠼ࠊ⡿ࡸᑠ㯏࡞࡝ࡢ✐≀࡟ྵ
ࡲࢀࡿ⧄⥔㉁ࡸ⢾ࢱࣥࣃࢡࢆ฼⏝ࡍࡿࡓࡵࡢ㑇ఏᏊࢆಖ᭷ࡋ࡚࠸ࡿ⳦ᰴࡶᏑᅾࡋ࡚࠸ࡿ
ࡇ࡜࠿ࡽࠊࡇࡢ✀ࡔࡅࡀᡂேࡸ㧗㱋⪅ࡲ࡛ᖜᗈ࠸ᖺ௦࡛⭠⟶࡟᳇ᜥࡋ࡚࠸ࡿ⌮⏤ࡢ୍➃ࡀ
♧ࡉࢀ࡚࠸ࡿ 15,16)ࠋࡇࡢࡼ࠺࡟ࠊࣅࣇ࢕ࢬࢫ⳦ࡣ᳇ᜥࡍࡿ⎔ቃ࡟ྜࢃࡏ࡚ྛ⳦✀࡟㐺ᛂ㐍
໬ࡋࡓ࡜⪃࠼ࡽࢀࡿࡀࠊ࡞ࡐࣄࢺ࡟ࡣ≉ᐃࡢࣅࣇ࢕ࢬࢫ⳦⳦✀ࡀ᳇ᜥࡋ࡚࠸ࡿࡢ࠿ࠊࡑࡢ
࣓࢝ࢽࢬ࣒࡟ࡣᮍࡔᮍゎ᫂࡞Ⅼࡀከࡃṧࡉࢀ࡚࠸ࡿࠋ

1.3. ...

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