**6. Conclusion**

320 Atopic Dermatitis – Disease Etiology and Clinical Management

Although oxa-fatty acids are widely used as intermediate chemicals in fine chemical fields such as medicine, agriculture and fragrance, there have only been a few reports of the antimicrobial activity of oxa-fatty acids. N-alkoxyacetic acid and its methyl ester showed good antifungal activity against *Aspergillus niger*, *Myrothecium verrucaria*, and *Trichoderma viride* (Gershon et al., 1979). In addition, 4-oxatetradecanoic acid, which is an inducer of myristic acid β-oxidation, displayed antifungal activity against *Cryptococcus neoformans* and also antiviral activity against human immunodeficiency virus I (Langner et al., 1992). These studies indicate that oxa-fatty acids of C16:1Δ6, in which the double bond has been replaced with an ether bond (7-oxaheptadecanoic acid or 6-decyloxy hexanoic acid), will maintain their antibacterial activity and will also have a novel function, that is antifungal activity.

An oxygen-containing analog of C16:1Δ6 (oxa-fatty acid:7-oxaheptadecanoic acid) was synthesized by condensation of *n*-decanol with 6-bromo-hexanoic acid under alkaline conditions. The antimicrobial activities of purified 7-oxaheptadecanoic acid were then compared with those of C16:1Δ6. The oxa-fatty acid analog of C16:1Δ6, 7 oxaheptadecanoic acid, retained the selective antimicrobial activity of C16:1Δ6, being effective against *S. aureus* but not against *S. epidermidis* (Fig. 11), and, displayed similar activity to C16:1Δ6 against *Propinibacterium acnes*, which is associated with AD (Ishibashi et al., 2009). In addition, 7-oxaheptadecanoic acid had gained an additional anti-yeast activity against *Malassezia*, which is associated with skin disorders such as seborrhea dermatitis and AD (Tajima et al., 2008). Moreover, the best molecule for treatment of skin disorders such as seborrhea dermatitis and AD could be selected by means of structure-

Fig. 11. Antibacterial activity of 7-oxaheptadecanoic acid. A: *S. aureus*; B: *S. epidermidis* 

**5.1 Review of the antimicrobial activities of oxa-fatty acids** 

**5.2 Synthesis and evaluation of a C16 oxa-fatty acid** 

activity relationships (Sugai et al., in preparation).

We found that *cis*-6-hexadecenoic acid (C16:1Δ6) displayed a selective antimicrobial activity that was unique among human sebaceous lipids. It was suggested that topical application of C16:1Δ6 to the skin of AD patients, who have lower levels of C16:1Δ6 in skin lipids than healthy controls, was effective for treatment of this skin condition. We proposed an industrial process for the production of C16:1Δ6 using *Rhodococcus* sp. An oxygencontaining analog of C16:1Δ6 (7-oxaheptadecanoic acid) was found to be more effective against microorganisms such as *S.aureus* and *Malassezia* sp. that are associated with skin disorders. It was proposed that the best oxa-fatty acid derivative of C16:1Δ6 could be selected by analysis of structure-activity relationships.

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**20** 

*Switzerland* 

**Probiotics and Atopic Dermatitis** 

The term "probiotic" was only coined starting from 1953 and means "for life" ("pro = for" and "bios = life") as opposed to "antibiotics". Yet, the related concept dates back to the early 1900s when Tissier and Metchnikoff pioneered the notion that not all bacteria are detrimental and that some may even be ingested for benefit of health and longevity (Tissier, 1906; Metchnikoff, 1908). Since then, over 9000 articles and 700 clinical trials have been devoted to document and unravel the beneficial effects attributed to probiotic strains and the mechanisms of action that may be involved. The health benefits attributed to probiotics are numerous (Nomoto, 2005; Nova et al., 2007; O'Hara and Shanahan, 2007; Parvez et al., 2006; Salminen et al., 2005; Sanders, 2008; Santosa et al., 2006) but the level of proof supporting them is highly variable depending on the benefit and more importantly on the studied strain. In view of the large diversity and the high number of probiotic candidate strains it is important to stress that most observations are strictly strain specific which means that data obtained on a given strain may not be extrapolated to all strains belonging to the corresponding bacterial species and genus. This renders a global analysis of the field

The adult human gastro-intestinal tract (GIT) houses about 1014 microbial cells, that outnumber by a factor of 10 the number of cells that compose the human body. This complex microbiota contains over 1000 bacterial types whose number and composition vary along the GIT as a consequence of the different biochemical conditions in the intestine, nutrient availability, age and health status of the host. Of note, the corresponding pool of genes (microbiome) is 150 times larger than the human genome (Eckburg et al., 2005). For this reason, the gut microbiota is sometimes referred to as an organ by itself. It is well established today that this complex microbial community plays an essential role in health and well being. Research conducted with germ-free or gnotobiotic (*i.e.* germ-free animals that were colonized by known bacteria) rodents has unambiguously demonstrated that even if germ free animals are viable when housed in specific conditions and fed with a very nutritious diet, the gut microbiota plays a critical role for normal growth and development

The GIT of mammals is sterile at birth but it becomes rapidly colonized by maternal and environmental bacteria during the delivery. The successive installation of bacterial species

quite difficult and general conclusions often lack accuracy.

**2. Human gut microbiota** 

(Kelly et al., 2007; Sjogren et al., 2009).

**1. Introduction** 

Feriel Hacini-Rachinel, Ivana Jankovic, Anurag Singh and Annick Mercenier

*Nestlé Research Center, Lausanne* 

