It is becoming increasingly clear that the gut microbiota or gut environment is intimately involved in health promotion and the development of lifestyle-related diseases. Advances in measurement technologies such as next-generation sequencers and mass spectrometers are bringing us new methodologies to investigate food function. The present status of gut microbiome research and specific examples of research targeting the intestinal environment were introduced.

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 Extension of healthy life expectancy is one of the important issues in Japan. The causes for need of long-term care are dementia in the first place, cerebrovascular diseases (stroke) in the second place and weakness due to aging or frailty in the third place. Therefore, effective measures to prevent those diseases and condition are urgent.
 It is recommended to have healthy lifestyles such as appropriate diet and exercise habits, maintain proper weight and stop smoking. In addition to these, from the view point of the current scientific evidence, proper use of dietary supplements and health foods containing functional food materials can contribute to the extension of healthy life expectancy.
 The introduction of mandatory fortification of grains with folic acid in 1998 in the United States resulted in declined the stroke mortality rate and decreased the prevalence of dementia. Even though Japanese government has no policy for mandatory fortification of folic acid, some local governments have introduced the usage of folic acid supplementation as their policy.
 Effective measures against frail/frailty and sarcopenia are important to prevent weakness due to aging. Glucosamine as a functional food material also attracts attention, as joint diseases are the main reason for disability for elderly. Recent clinical trials such as MOVES and LEGS trials confirmed the efficacy of glucosamine for knee osteoarthritis. In addition, PROOF trail showed the efficacy of glucosamine to prevent knee OA.
 Today, where the extension of healthy life expectancy is set as the goal of the country, several new efforts by public-private partnership between local governments and healthcare companies have been carried out. In this context, the utilization of functional food materials / functional foods is considered to be one of the important measures for achieving healthy longevity in an aging society.

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 The severity and frequency of joint loading are principal factors for the development of joint disorders, which is characterized by the articular cartilage damage. Thus, sports with repetitive impact and torsional loading on the joints enhance the risk of articular cartilage degeneration, and result in the clinical symptoms of osteoarthritis. Among sports with various different frequency and intensity of joint loading, soccer is categorized as a representative with high levels of repetitive impact and torsional loading on the joint. Interestingly, nutritional supplements such as glucosamine are often administered for “joint health” of sports-related cartilage injuries (osteoarthritis) in athletes. Moreover, reliable and sensitive biomarkers have been recently developed as indicators of cartilage metabolism in subjects with joint disorders. Thus, in this paper, the effect of glucosamine administration on the cartilage metabolism in soccer players, as determined by the markers for type II collagen degradation (CTX-II and C2C) and synthesis (CPII), are presented.

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 Glucosamine (2-amino-2-deoxyglucose, GlcN), a naturally occurring amino monosaccharide, has been widely used to treat osteoarthritis (OA) in humans. However, the effects of GlcN on autophagy in chondrocyte are still unknown. In this study, to elucidate the chondroprotective action of GlcN via autophagy, we evaluated the effect of GlcN on the expression of autophagy-related molecules (LC3-II, Beclin-1, ATG5 and ATG7) using a human chondrocyte cell line Hs 819.T. GlcN significantly increased protein level of LC3-II and mRNA expression of Beclin-1, ATG5 and ATG7. Moreover, GlcN significantly increased the protein level of SIRT1. Importantly, the GlcN-induced increase of LC3-II protein was inhibited by EX527 (a SIRT1 inhibitor). Moreover, GlcN did not effect the S6K phosphorylation, as a target of mammalian target of rapamycin (mTOR). In addition, GlcN significantly decreased the acetylation (activation) of p53, which negatively regulates autophagy independent of mTOR.
 Together these observations suggest that GlcN increases the expression of SIRT1 and possibly induces autophagy through the suppression of p53 activity in chondrocytes independent of mTOR, thereby exhibiting the chondroprotective action.

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  Scutellaria baicalensis Georgi root is traditionally used as a Chinese herbal medicine that has anti-pyretic and anti-inflammatory properties. In addition to these traditional uses, recent studies have shown that S. baicalensis has a lightening effect on skin pigmentation. The identity of the active ingredient responsible for its skin pigmentation-lightening effect or its mechanism of action is still unclear. This study reports three major findings: (1) S. baicalensis exhibits the highest inhibitory activity against melanogenesis among the 137 species of herbal plants tested; (2) an O-methylated flavone, wogonin, was identified as the active component of S. baicalensis that inhibits melanogenesis; and (3) the microphthalmia-associated transcription factor (MITF), is the probable target of wogonin to induce melanogenesis suppression. In addition, we found that wogonin inhibits the intracellular transport of melanosomes in melanocytes, suggesting that wogonin has bi-functional effects in terms of depigmentation. Several wogonin analogs and other major flavones present in S. baicalensis failed to inhibit intracellular trafficking of melanosomes, highlighting the unique effect of wogonin. Moreover, wogonin specifically decreases the concentration of the melanophilin (MLPH) protein but not that of other actin-based melanosome-transport-related molecules. Our findings reveal the potential applicability of S. baicalensis, which comprises wogonin and other flavones, in skin lightening and treating hyperpigmentation.

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 Lactobacillus acidophilus L-92 (L-92) has been selected as a lactic acid bacterium expected to have anti-allergic function. We showed that ingestion of foods containing L-92 could alleviate allergic symptoms caused by type I allergic reactions such as perennial allergic rhinitis or atopic dermatitis in human clinical trials. In this article, we report the effects of oral administration of L-92 on symptoms of pollen allergy.
 Subjects ingested tablets containing 20.7 mg of L-92 per day for 12 weeks and assessed their nasal and ocular symptoms scores every day. As a result, the sneeze scores showed significantly lower level ​​compared to the placebo group at 12 weeks. In addition, the itch eye score and ocular symptom-medication score were significantly compared to the placebo group during the test period. Antigen - specific IgE level in L-92 group was reduced compared with the placebo group in the 12-week period.
 These results show that oral administration of L-92 could alleviate the symptoms of pollen allergy.

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 The consumption of Citrus unshiu ( C. unshiu ) is decreasing in recent years and the C. unshiu farmers’ income is going down. The aim of this study is to boost the use of immature C. unshiu , which is currently discarded. This research focused on the effect of immature C. unshiu powder (ICP) on the photoaged skin. ICP was orally administered at dose of 200 mg/ kg body weight / day to six-week old male hairless mice for seven weeks. Through the whole experiment, UVB was irradiated at their dorsal skin three times a week. As UVB irradiation reduces skin moisture content and increases transepidermal water loss, these skin barrier disruptions are triggering wrinkle formation. Oral administration of ICP improved these symptoms. The histological analysis of hairless mice dorsal skin revealed that oral administration of ICP improved overgrowth of epidermal cell and decreased the number of dead cells. Hyaluronan content in the skin was analyzed with ELISA was increased in the ICP-treated mice. These findings suggest that ICP may have the anti- photoaging activity by restoring skin barrier function. These results showed that ICP has a potential to be used as a functional food.

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 Catechins, such as catechin, epicatechin (EC), epigallocatechin (EGC) and epigallocatechin gallate (EGCG), are polyphenols contained in green tea. Catechins exhibits various biological functions including antioxidative activities; however, the effects of catechins on bone metabolism are still unclear.
 We have reported that EGCG and methylated EGCG (EGCG3’’Me), methylated derivative of EGCG, exerted the bone protective effects against an experimental periodontitis model.
 Both EGCG and EGCG3’’Me inhibited osteoclast differentiation and bone resorption. In osteoblasts, EGCG and EGCG3’’Me directly attenuated IκB kinase (IKK) activity, leading to the inhibition of osteoclast differentiation through the decreased production of prostaglandin (PG) E₂ and receptor activator of NF-κB ligand (RANKL).
 We further showed that EGCG and EGCG3’’Me suppressed LPS-induced bone resorption of alveolar bone in an experimental periodontitis model.
 The intake of EGCG has also shown to inhibit the estrogen deficiency-induced bone loss in ovariectomized animal model. Since it is the important issues to prevent the bone loss in super-aging society, catechins are the candidates for the prevention of bone-related diseases. This review described the effects of catechins on bone diseases including periodontitis and postmenopausal osteoporosis.

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 Glucosamine exhibits a protective action on joint disorders accompanying pain and loss of motion, based on its anti-inflammatory action. We have revealed that glucosamine downregulates the expression of IL-8 gene via O-linked-N-acetylglucosamine (O-GlcNAc) modification, a post translational modification of proteins involved in the modulation of several cellular functions. Importantly, the transcription factor NF-κB (p65/p50 heterodimer) regulates the production of proinflammatory molecules. Thus, in this study, we investigated the effect of glucosamine on the activation of NF-κB, and the role of O-GlcNAc modification in NF-κB activation using a synovial cells line MH7A.
 Glucosamine inhibited the IL-1β-induced phosphorylation and nuclear translocation of NF-κB p65 subunit. Glucosamine also inhibited the IL-1β-induced dissociation of IκBα (the NF-κB inhibiting protein) from NF-κB. Importantly, alloxan, an O-GlcNAc transferase inhibitor, which inhibits O-GlcNAc modification, abolished the glucosamine-mediated inhibition of the phosphorylation, translocation of NF-κB and dissociation of IκBα.
 Together these observations suggest that glucosamine suppresses the activation of NF-κB (phosphorylation and nuclear translocation) by the inhibition of IκBα dissociation from NF-κB via O-GlcNAc modification.

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 Nishio et al. proposed the production of a novel sugar, N-acetylsucrosamine, by transglycosylating β-fructofuranosidase in the presence of sucrose and N-acetylglucosamine, and has been successful in this isolated crystallization. In addition, this heterodisaccharide can be expected as source of prebiotics as it selectively propagates a specific strain of Bifidobacterium in large intestine without being digested and absorbed in the small intestine. Therefore, in this study, commercial Kome Koji was used to ferment in the presence of sucrose and N-acetylglucosamine.
 As a result, N-acetylscrosamine, GlcNAc, Glc, and fructo oligosaccharides were formed in the medium, and sucrose which is the raw material, almost disappeared. Even if the fermented culture fluid is powdered or powdered with Aspergillus oryzae together, it may be possible to develop an interesting new food as a fermented food as prebiotics.

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Background： Rheumatoid arthritis (RA) is an immune-mediated disease and causes systemic articular destruction. Recent development of novel drugs has ameliorated the disease activity and improved nutritional status. As supplement use in patients with RA is largely unknown, however, a questionnaire survey was conducted.
Study design： RA outpatients in our institutes (12male and 85female) participated in this study and filled in a questionnaire. This study was approved by the ethics committee.
Results： Out of the patients, 51% of them used supplements and only 13 % of them for RA. Polyunsaturated fatty acid (PUFA) was used in 6 patients, lactic acid and calcium were used in 4 patients respectively, and glucosamine, chondroitin, collagen and coenzyme Q10 were used in 2 patients respectively. Polyphenol, enzyme, aojiru and herb were also used in a patient respectively.
 One third of patients who used supplement for RA estimated them effective. The monthly cost of supplement was less than ¥3000 in 15, ¥3000-8000 in 19 and over ¥8000 in12 patients.
Conclusion： A half of RA patients were revealed to use diet supplements, however only 13% of patients used them for RA itself. PUFA was the most prevalent supplement in RA. Seventy percent of patients hoped to continue some supplements or use them in the future.

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