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aTMC, Culture Collection of Takanashi Milk Products Co., Ltd.; ATCC, American Type Culture Collection; JCM, Japanese Collection of Microorganisms.

bMean of bacteria cells bound to Caco-2 cell in 20 randomly chosen microscopic fields ( —); 0; ( + ): 1-20; (+ +): 21-50; (+ + +): 100-200.

cIL-6 secretion by Caco-2 cells was expressed as Mean (SD); —: <0.7 pg/ml (detection limit).

dIL-8 secretion by Caco-2 cells was expressed as Mean (SD); —: <10 pg/ml (detection limit).

Abbreviation: IL, interleukin.

B. bifidum, B. breve, and B. infantis. In contrast, B. adolescentis did not stimulate the production of anti-inflammatory IL-10 as the other tested bacteria did. At the same time, neither the adult-type nor the infant-type bifidobacteria were found to be likely to trigger inflammatory responses in human enterocytes (Table 2) (64). The results suggest that the adult-type bifidobacteria, especially, B. adolescentis, may be more potent to amplify but less able to down-regulate the inflammatory responses (Table 3).

The intestinal microbiota of elderly people is in general different from those in infants; the former is more diverse and stable (8). One of the distinct age-related events in intestinal microbiology is the increase in numbers of facultative anaerobic Gramnegative bacteria (8); these bacteria may be opportunistic infective agents. They have been found to be the triggers of anti-inflammatory cytokine-production by macrophages and monocytes (60,61). The anti-inflammatory effects of these bacteria are believed to be one of the strategies required for their successful colonization of the host's intestine, overcoming the natural defense barrier, including inflammation. Therefore, an increase in bacteria, including bifidobacteria, which can enhance the intestinal inflammatory response in aged people, can be considered beneficial to counterbalance the age-related changes in their intestinal microecology. This may contribute to the homeostasis of the local immunity by preventing local inflammation from being oversuppressed. These results suggest that the dominance of the intestinal bifidobacteria by B. adolescentis may be one of the events in the intestinal environment in response to the aging of the host.

These results can lead to a hypothesis that the age-related changes of the predominant species of bifidobacteria in the human intestine is a kind of well-acquired adaptation of the host to the changes in the intestinal microbiota, localizing the beneficial microbes such as B. adolescentis to enhance the colonization resistance against the exogenous infectious agents. For more information on the influence of the normal intestinal microbiota on the immune system, see the chapter by Moreau.

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