Diversity of Halophilic Archaea in Fermented Foods and Human Intestines and Their Application
Diversity of Halophilic Archaea in Fermented Foods and Human Intestines and Their Application
Journal of Microbiology and Biotechnology. 2013. Dec, 23(12): 1645-1653
Copyright © 2013, The Korean Society For Microbiology And Biotechnology
  • Received : August 08, 2013
  • Accepted : September 09, 2013
  • Published : December 28, 2013
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About the Authors
Han-Seung, Lee
Research Center for Extremophiles, Silla University, Busan 617-736, Republic of Korea

Archaea are prokaryotic organisms distinct from bacteria in the structural and molecular biological sense, and these microorganisms are known to thrive mostly at extreme environments. In particular, most studies on halophilic archaea have been focused on environmental and ecological researches. However, new species of halophilic archaea are being isolated and identified from high salt-fermented foods consumed by humans, and it has been found that various types of halophilic archaea exist in food products by cultureindependent molecular biological methods. In addition, even if the numbers are not quite high, DNAs of various halophilic archaea are being detected in human intestines and much interest is given to their possible roles. This review aims to summarize the types and characteristics of halophilic archaea reported to be present in foods and human intestines and to discuss their application as well.
Archaea refer to prokaryotes that used to be categorized as archaeabacteria, a type of bacteria, in the past. After Carl Woose’s pioneering classification by phylogenetic taxonomy of the 16S ribosomal RNA [63] , they are considered as an independent domain rather than being categorized as bacteria because the metabolism of archaea related to central dogma is closer to that of eukaryotes and the structure of the cell wall is significantly different from bacteria. Until now, archaea have been classified into 5 phyla ( Crenarchaeota , Euryarchaeota , Korarchaeota , Nanoarchaeota , and Thaumarchaeota ) based on the phylogenetic method [10] , and they are sometimes categorized as thermophilic, halophilic, and methanogenic archaea according to the growth properties of the strains. Archaea are sometimes referred to as extremophiles because an “extreme” environment is needed for the growth of these strains or because such optimal growth often takes place in an extreme environment. However, not all archaea are extremophiles, and there are other species of bacteria or eukaryotes that grow in an extreme environment as well.
Depending on the optimal salt concentration needed for the growth of strains, halophilic microorganisms can be classified as halotolerant (~0.3 M), halophilic (0.2~2.0 M), and highly halophilic (3.0~5.0 M) [29] , and most of halophilic archaea belong to the highly halophilic category. Among the highly halophilic archaea, those that especially need a minimum salt concentration of 1.5 M (9% w/v) to 2.5 M (15% w/v) are referred to as extremely halophilic archaea or haloarchaea, in general [11] .
Halophilic archaea have been classified into a single family of the Halobacteriaceae in which 40 genera and more than 150 species are included [35] . Most of them are known to live in environments like salt lakes or salterns with very high salt concentrations. However, as new halophilic archaeal strains have been continuously identified by screening methods utilizing several new compositions of culture media, it has recently been reported that halophilic archaea exist in salted food products or fermented foods as well. In addition, people have become aware that halophilic archaea exist much closer to the surrounding human environments, as metagenomic analyzing methods are developed. Moreover, some new techniques that are able to detect very small amounts of DNA have also brought awareness about the existence of halophilic archaea in the intestines of animals. Accordingly, this study aims to understand the types and characteristics of halophilic archaea that have been reported to be present in food products and animal intestines, which are gradually receiving more attention, and also to discuss their applications.
Halophilic Archaea in Foods Identified by Culture-Dependent Methods
Diverse types of salted foods or high salt-fermented foods exist worldwide because salt has been used for a very long time to preserve food. Although salt had been known only to restrain the growth of food-poisoning bacteria and to promote the growth of fermentating bacteria such as yeast and lactic acid bacteria, new types of halophilic archaea are recently being identified in fermented food products with high salt concentration ( Table 1 ). The existence of halophilic archaea in salted foods may be due to salterns being one of the important environments for their growth, so salt produced from these salterns would contain haloarchaea [23 , 53 , 55] . Among fermented foods, new types of halophilic archaea have been discovered in fermented fish and fish sauces that require a large amount of salt, and such studies are being conducted mostly in Korea, Japan, and Southeast Asian countries, despite the fact that various types of fermented fish and shellfish products are present worldwide.
Halophilic archaea isolated from fermented foods and salts.
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aThe strain is magnesium-dependent, and the optimal NaCl concentration is in the presence of 2% (w/v) MgCl2·6H2O.
- Halophilic Archaea in Korean Foods
It is the predominant view that an excessive sodium intake is having a negative influence on the health of the Korean population, since a Korean’s daily salt consumption is approximately 13 g [20] , which is more than twice the recommended dietary intake of WHO. In addition, while one of the major causes of death in Korea is cancer, some evidence suggests that the higher rate of gastric cancer, as opposed to other cancers, is related to high sodium consumption [2 , 22] . Among Korean traditional foods, there are many high salt-fermented foods that include soy-fermented products, such as soy sauce and soybean paste; and fermented seafoods, such as jeotgal (fermented small fish or shellfish) and sikhae (fermented fish with salt and starchy grains). Specifically, jeotgal , Korea’s very own condiment, contains the highest concentration of salt (more than 20% (w/v) NaCl) among high salt-fermented foods, and 164 types of jeotgals are being made nationwide [18] .
Halophilic archaea isolated from Korean foods using culture-dependent methods include Haladaptatus cibarius [44] , Halalkalicoccus jeotgali [47] , Halorubrum cibi [42] , Haloterrigena jeotgali [45] , and Natronococcus jeotgali [46] from various types of jeotgals , and also Halogranum salarium [23] from bay salt. Their characteristics are shown in Table 1 . Whereas most halophilic archaea are extreme halophiles that grow in salt concentrations of at least 10% (w/v) NaCl, with optimal salt concentration for growth being at least 20% (w/v; approx. 3.4 M), Haladaptatus cibarius and Halalkalicoccus jeotgali showed optimal growth with 15% (w/v) NaCl concentrations, which is relatively low to be referred to as extreme halophiles. In particular, archaea that belong to the genus Haladaptatus have been thought to adapt to low salt concentrations. In the case of Haladaptatus paucihalophilus , which was isolated for the first time as the genus Haladaptatus , it can even grow in very low NaCl concentrations (higher than 0.8 M) [50] . Owing to these reasons, it is expected that the possibility of the existence of archaea belonging to the genus Haladaptatus in fermented foods with relatively moderate salt concentrations is high.
- Halophilic Archaea in Foods Outside Korea
Halophilic archaea that have been identified in foods outside Korea so far are mostly from Japan and Southeast Asia, especially from Thailand. Almost 80~90% of the total population in Southeast Asia are known to consume fish sauce [4] , unlike the Korean and Japanese, who normally use soy sauce for fermented condiments. In particular, Thai fish sauce is well known worldwide as a seasoning for Thai cuisine. Fish sauce, similar to liquid jeotgal in Korea ( ackjeot ), refers to the filtered liquid obtained by adding table salt of 20~30% (w/v) to fish or shellfish and by allowing it to ferment for a long time. Most representative Thai fish sauces include nam-pla, which is similar to Korea’s fermented anchovy ackjeot , and pla-ra, which is fermented by adding starchy grains to fish and salt. Tapinkae et al . [60] have identified 156 species of halophilic archaea from various fish sauce products, and new species of halophilic archaea are continuously being reported ( Table 1 ). New strains of halophilic archaea that have been isolated from Thai fish sauce so far include Halobacterium salinarum (H. piscisalsi) [28 , 64] , Natrinema gari [59] , Haloarcula salaria [32] , Haloacular tradensis [32] , and Halococcus thailandensis [33] . Most of these strains show similar characteristics since a minimum salt concentration of 15% (w/v) is needed for growth, and the optimal salt concentration for growth is at least 20% (w/v).
There are various fermented foods with high sodium concentration in Japan and the likelihood of the existence of haloarchaea has been reported [24] . Japanese researchers have recently reported that halophilic archaea have been isolated from bay salts that are sold commercially in Japan. The fact that halophilic archaea are still alive in salts after being heated by the sun in salterns and dried for at least 10 days suggests that the chances for halophilic archaea to come in contact with humans are much higher than expected. Halophilic archaea that have been isolated and identified from Japanese commercial salts include Salarchaeum japonicum [53] , Halobaculum magnesiiphilum [55] , Natronoarchaeum mannanilyticum [54] , Halarchaeum acidiphilum [26] , and Halostagnicola alkaliphila [30] , and these halophilic archaea show a much wider variety of growth conditions compared with those isolated from high salt-fermented foods. Whereas most halophilic archaea are mesophilic, Halobaculum magnesiiphilum [55] can grow in temperatures up to 55℃ (optimal growth temperature is 45℃), and it also grows in 30% (w/v) MgCl 2 concentration since it is magnesium-dependent.
In addition, there are some acidophilic haloarchaea like Salarchaeum japonicum [53] and Halarchaeum acidiphilum [53] , and alkalophilic haloarchaea like Natronoarchaeum mannanilyticum [53] , showing diverse pH-dependent characteristics. Therefore, it is expected that screening with culture media of various pHs when examining haloarchaea in food products would allow us to study many more varieties of halophilic archaea.
The number of halophilic archaea isolated and identified from foods in and outside Korea by culture-dependent methods is not large. This may be due to conventional screening methods of halophilic archaea that focused on environments around salt lakes or salterns, and the lack of attempts to design new screening media, because of the assumption that the possibility of their existence in foods was low. However, based on the fact that the halophilic archaeal strains isolated until now are very diverse, it needs to be considered that the possibility of having a wide variety of halophilic archaea in food products is higher than would have been expected in the past.
Halophilic Archaea in Foods and Human Intestines Identified by Culture-Independent Techniques
Although culture-dependent methods have been used to analyze microflora within foods or environments for the past few years, there are limitations on the number of microorganisms that researchers can culture with conventional methods. Therefore, culture-independent techniques such as PCR and denaturing gradient gel electrophoresis (PCR-DGGE), library cloning, restriction fragment length polymorphism (RFLP), or next-generation sequencing (NGS) are rapidly being developed for analyzing microflora or microbiomes [62] .
- Identification of Halophilic Archaea in Foods by Using Culture-Independent Techniques
Studies that have been conducted to explore halophilic archaea in foods by using PCR-DGGE only include research on jeotgal [43] and kimchi [12] of Korea and pickled olives [1] from the Mediterranean regions, and strains identified through such methods that match the closest to the genetic sequence of the 16S rRNA gene of halophilic archaea are shown in Table 2 . Interestingly, although Halalkalicoccus jeotgali , Natrialba aegyptiaca, and Natronococcus jeotgali isolated by culture-dependent methods were also found in results of PCR-DGGE of jeotgal and kimchi samples, DNAs of other strains were not found. However, DNAs of Halorhabdus utahensis, Halorubrum lipolyticum, Halorubrum luteum, Halorubrum sp. YYJ21, Halovivax ruber , and other strains were identified from seven types of jeotgals [43] . In the case of kimchi , there were changes of PCR-DGGE profile as fermentation progressed, and there was a relatively large number of DNAs for strains such as Halococcus spp., Natronococcus spp., Natrialba spp., and Haloterrigena spp. [12] .
Culture-independent identification of halophilic archaeal 16S rRNA gene sequences of DGGE bands from fermented foods.
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Culture-independent identification of halophilic archaeal 16S rRNA gene sequences of DGGE bands from fermented foods.
Aside from the PCR-DGGE method, barcoded pyrosequencing, which is one of the NGS methods, was used in Rho et al .’s [43] studies on microbial diversity in jeotgal . Their studies showed that 68.6~98.4% of strains of the phylum Euryarchaeota in jeotgal belonged to the family Halobacteriaceae , among which most were found to be Halorubrum and Halalkalicoccus genera. Furthermore, Park et al. [37] used qPCR (quantitative real-time PCR) to enumerate the changes of archaea during the fermentation process of kimchi , and it was found to be maintained from the early stage to day 17 of fermentation.
Olive farming takes a great part in Mediterranean agriculture, and not only the well-known olive oil but also green table olives, a type of pickled product of olives submerged in salt water of 6~8% (w/v) for at least 6 months, are popular foods in that area. Abriouel et al . [1] analyzed the diversity of microbial populations by PCRDGGE after obtaining samples by differing the period and method of fermentation from green table olive fermenting companies in the Malaga region of Spain. This study showed that Halosarcina pallida and Halorubrum orientalis were extensively present in the products. In summary, archaea belonging to the Halorubrum genus that has been seldom isolated by culture-dependent methods may be present in various food products.
- Halophilic Archaea Inside Human Intestines
The number of microbiomes that live inside the human body is extremely larger, reaching to approximately 10 13 ~ 10 14 CFU, and the size of their genome is close to 100 times bigger than that of the human genome [15] . In particular,according to recent studies, microorganisms that live inside human intestines are known to be one of the factors forcontrolling fat storage and also to be related to obesity [6 , 25] . Although more than 90% of these enteric microorganisms are bacteria that belong to divisions of Bacteroidetes and Firmicutes, it is reported that if Firmicutes strains are greater in number than Bacteroidetes strains, the person is more likely to become obese since substances that are hard to digest are digested.
Unlike bacteria, the number of archaea among the enteric microbiomes is very small, most of which are presumed to be methanogenic archaea [49] . Among the methanogenic archaea, Methanobrevibacter smithii belongs to the phylum Euryarchaeota that takes up nearly 10% of anaerobic microorganisms present in the colon of an healthy adult, which is known to play a central role in removing hydrogen inside human intestines [49] . On the other hand, in the case of halophilic archaea, it had been thought in the past that the low salt concentrations inside human intestines is inadequate for halophilic archaea to survive, but there have been reports [40] that there are halophilic archaea that can survive in salt concentrations close to sea water (approx. 2.5% )undefined(w/v)). In addition, Oxley et al . [36] have succeeded in identifying DNAs of various halophilic archaea from colonic mucosal biopsies and fecal samples of patients, commercially sold salts, etc . Interesting to note is that diversity is quite low for methanogenic archaea inside intestines since most of them belong to the three species Methanobrevibacter smithii , Methanosphaera stadtmanae , and Methanobrevibacter arboriphilus , whereas on the other hand, enteric halophilic archaea have a relatively greater variety, mostly belonging to the genus Halorubrum .
These results above also correspond to the results of Nam et al.’ s [31] study that conducted PCR-DGGE in order to explore the diversity of enteric archaea from fecal samples of Koreans. In this study, DNAs obtained from feces included not only those of methanogenic archaea but also 16S rDNA of strains similar to Halorubrum koreense, Halorubrum alimentarium, Halorubrum saccharovorum, and Halococcus morrhuae. In our research laboratory, investigation of halophilic archaea from human fecal samples by using a culture-dependent method resulted in identification of DNAs that all belonged to the genus Halorubrum (data unpublished). The genus Halorubrum contains very diverse haloarchaea, but it may have special characteristics to be detected. It seems that future studies are needed on why Halorubrum is frequently detected as enteric halophilic archaea.
Industrial Usage of Halophilic Archaea
Although there have continually been attempts for using genetic resources and proteins of halophilic archaea for industrial usages, the current status remains mostly in their potential. In particular, there have been studies conducted in the food industry for using haloarchaea in fermentation and the ripening process of foods such as fermented anchovy ackjeot or fish sauce that require over 1 year of ripening [5] . It is because various enzymes, including proteases, produced by halophilic archaea promote the ripening of fish sauce, through which desired flavor is achieved in the product. In particular, proteases of halophilic archaea are receiving the most attention, and their potential for use is being widened by purification and cloning from several strains ( Table 3 ). Most of the proteases reported from halophilic archaea are extracellular serine proteases that have characteristics of maintaining their activity even in high salt concentrations.
Proteases from halophilic archaea.
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aN.D. means “not determined”.
Akolkar et al. [4] have reported that the fermentation period of fish sauce was shortened, in addition to having an improved amino acid profile that is responsible for flavor when Halobacterium sp. SP1(1) that produces protease was used as a starter for fish sauce. Moreover, Aponte et al . [5] studied the effects of halophilic archaea on the quality and safety of salted anchovies ( Engraulis encrasicolus ), which are traditional foods in the Mediterranean region. The results of this study, comparing the addition of Halobacterium salinarium CER6a that produces protease versus Haloarcula marismortui 1R strain that has no protease activity, showed that according to a preference survey conducted through sensory test, people preferred salted anchovies with addition of haloarchaea more than the control group despite having no significant differences in the hydrolytic rate of muscle sarcoplasmic protein. The most interesting fact is that in the case of salted anchovies with addition of haloarchaea, production of histamine, which is an anti-nutritional factor, was inhibited during the initial ripening process.
Histamine, which is a representative bionic amine, found much in fish such as mackerels, sauries, and sardines, is an important factor that must be inhibited in fermented foods. Intake of histamine causes scombroid poisoning leading to various toxicities such as rash, hives, nausea, vomiting, diarrhea, flushing, among others [8] , and so the US FDA regulates the concentration of histamine to be below 500 ppm, over which would lead to toxicity in humans. Development of methods for reducing histamine is in much need because such histamine is not only produced by fermenting bacteria but is also very stable and hardly broken down except through gamma radiation. Study results of Tapingkae et al . [60] , in which strains with histamine breakdown activity were examined among the 156 strains of halophilic archaea isolated from anchovy fish sauce, showed that the histamine breakdown activity was present in 60 strains and that the strain (HDS1-1) with the strongest activity was Natrinema gari. Accordingly, it is considered that using halophilic archaea as a starter for fermented foods would not only shorten the fermenting period and improve on flavor but also increase the safety of the food product.
Halocin orthologs from halophilic archaea.
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aORF number from genome sequencing data.
Among the proteinous substances produced by halophilic archaea, halocin has the highest potential of uses. Halocin is an antibiotic substance in the form of a small-molecule protein that is produced by most of the rod-type haloarchaea, and until now, not many of its physical and chemical properties characterized from purification have been elucidated; the characteristics of only three halocins have been cloned and studied [13 , 39 , 58] . However, as NGS technology is being developed and the genomic sequence of halophilic archaea is continuously being reported, orthologs with a similar amino acid sequence to halocin are receiving attention as the new halocin. Although the antibiotic spectrum of halocin has been not studied in detail, the potential for its application can be said to be great since there are no antibiotic substances that can selectively kill archaea for now.
Aside from the above, studies on halophilic archaea of the genus Haloferax are being conducted because these archaea produce either extracellular polysaccharides [34 , 38] or biopolymers like polyhydroxyalkanoates [17 , 41] . It is also expected that halophilic archaea could be used for biodegradation of food wastes that contain high salt concentrations and also for treatment of saline wastewater.
Future Outlook
Until now, halophilic archaea have mostly been studied in the environmental and ecological fields, but recently, it is discovered that they have close relationships with daily human life. There have not been many reports of halophilic archaea found in salted foods or animal intestines. This is likely due to the lack of researchers’ interest on isolation of strains. Accordingly, there will be continued trials for isolation of strains that have not yet been reported.
Although halophilic archaea had been known to be unable to grow in salt concentrations below 10% (w/v) because cell lysis occurred by osmotic pressure, there are recent reports of halophilic archaea capable of surviving in low salt concentrations. Therefore, the possibility of continued findings of halophilic archaea strains adapting in foods or inside animal guts is high. Yet, the most important issue is how to develop the techniques to grow halophilic archaea by culture-dependent methods instead of DNA discovery through culture-independent methods. The success of culture of halophilic archaea adapting to environments with low salt concentrations would provide a good evidence for understanding adaptation mechanisms of microorganisms.
Moreover, in order to use haloarchaea and their useful enzymes and substances in the food industry, there must be accompanying studies on the safety of haloarchaea itself as well. Interestingly, there is growing interest in the relationship between archaea and infection, as methanogenic archaea Methanobrevibacter oralis have been found to be related to periodontitis [26] , but until now, there is lack of studies being conducted on the relationship between consumption of halophilic archaea and human health. In particular, there will be needs for future studies on the effects of halophilic archaea surviving in human intestines and studies on the special metabolism of halophilic archaea, because as the human microbiome is considered as another organ [9] , humans, bacteria, and archaea are known to have mutualism through metabolisms different from one another [7] .
This work was supported by grant 2010-0011707 from the National Research Foundation (NRF) of Korea.
Abriouel H , Benomar N , Lucas R , Galvez A. 2011 Culture-independent study of the diversity of microbial populations in brines during fermentation of naturally-fermented alorena green table olives. Int. J. Food Microbiol. 144 487 - 496    DOI : 10.1016/j.ijfoodmicro.2010.11.006
Ahn YO 1997 Diet and stomach cancer in Korea. Int. J. Cancer. Suppl 10 7 - 9
Akolkar AV , Desai AJ 2010 Catalytic and thermodynamic characterization of protease from Halobacterium sp. SP1(1). Res. Microbiol. 161 355 - 362    DOI : 10.1016/j.resmic.2010.04.005
Akolkar AV , Durai D , Desai AJ 2010 Halobacterium sp. SP1(1) as a starter culture for accelerating fish sauce fermentation. J. Appl. Microbiol. 109 44 - 53
Aponte M , Blaiotta G , Francesca N , Moschetti G 210 Could halophilic archaea improve the traditional salted anchovies (Engraulis encrasicholus L.) safety and quality? Lett. Appl. Microbiol. 51 697 - 703    DOI : 10.1111/j.1472-765X.2010.02956.x
Backhed F , Ding H , Wang T , Hooper LV , Koh GY , Nagy A 2004 The gut microbiota as an environmental factor that regulates fat storage. Proc. Natl. Acad. Sci. USA . 101 15718 - 15723    DOI : 10.1073/pnas.0407076101
Backhed F , Ley RE , Sonnenburg JL , Peterson DA , Gordon JI 2005 Host-bacterial mutualism in the human intestine. Science 307 1915 - 1920    DOI : 10.1126/science.1104816
Bang M , Chung C , Chang M , Lee S , Lee S 2009 Characteristics of histamine forming bacteria from tuna fish waste in Korea. J. Life Sci. 19 277 - 283    DOI : 10.5352/JLS.2009.19.2.277
Baquero F , Nombela C 2012 The microbiome as a human organ. Clin. Microbiol. Infect. 18 2 - 4    DOI : 10.1111/j.1469-0691.2012.03916.x
Brochier-Armanet C , Boussau B , Gribaldo S , Forterre P 2008 Mesophilic Crenarchaeota: Proposal for a third archaeal phylum, the Thaumarchaeota. Nat. Rev. Microbiol. 6 245 - 252    DOI : 10.1038/nrmicro1852
Capes MD , DasSarma P , DasSarma S 2012 The core and unique proteins of haloarchaea. BMC Genomics 13 39 -    DOI : 10.1186/1471-2164-13-39
Chang HW , Kim KH , Nam YD , Roh SW , Kim MS , Jeon CO 2008 Analysis of yeast and archaeal population dynamics in kimchi using denaturing gradient gel electrophoresis. Int. J. Food Microbiol. 126 159 - 166    DOI : 10.1016/j.ijfoodmicro.2008.05.013
Cheung J , Danna KJ , O’Connor EM , Price LB , Shand RF 1997 Isolation, sequence, and expression of the gene encoding halocin H4, a bacteriocin from the halophilic archaeon Haloferax mediterranei R4. J. Bacteriol. 179 548 - 551
Euzéby JP 1997 List of bacterial names with standing in nomenclature: a folder available on the Internet. Int. J. Syst. Bacteriol. 47 590 - 592    DOI : 10.1099/00207713-47-2-590
Gill SR , Pop M , Deboy RT , Eckburg PB , Turnbaugh PJ , Samuel BS 2006 Metagenomic analysis of the human distal gut microbiome. Science. 312 1355 - 1359    DOI : 10.1126/science.1124234
Gimenez MI , Studdert CA , Sanchez JJ , De Castro RE 2000 Extracellular protease of Natrialba magadii: purification and biochemical characterization. Extremophiles 4 181 - 188    DOI : 10.1007/s007920070033
Han J , Lu Q , Zhou L , Liu H , Xiang H 2009 Identification of the polyhydroxyalkanoate (PHA)-specific acetoacetyl coenzyme A reductase among multiple FabG paralogs in Haloarcula hispanica and reconstruction of the PHA biosynthetic pathway in Haloferax volcanii. Appl. Environ. Microbiol. 75 6168 - 6175    DOI : 10.1128/AEM.00938-09
Hur S 1996 Critical review on the microbiological standardization of salt-fermented fish product. J. Kor. Soc. Food Sci. Nutr. 25 885 - 891
Izotova LS , Strongin AY , Chekulaeva LN , Sterkin VE , Ostoslavskaya VI , Lyublinskaya LA 1983 Purification and properties of serine protease from Halobacterium halobium. J. Bacteriol. 155 826 - 830
Jang J , Kim M , Han J 2009 A study on food frequency,dietary habits and nutrition knowledge of the elderly who intake high sodium. J. Kor. Soc. Food Sci. Nutr. 38 1362 - 1372    DOI : 10.3746/jkfn.2009.38.10.1362
Kamekura M , Seno Y , Holmes ML , Dyall-Smith ML 1992 Molecular cloning and sequencing of the gene for a halophilic alkaline serine protease (halolysin) from an unidentified halophilic archaea strain (172P1) and expression of the gene in Haloferax volcanii. J. Bacteriol. 174 736 - 742
Kim J , Park S , Nam BH 2010 Gastric cancer and salt preference: a population-based cohort study in Korea. Am. J. Clin. Nutr. 91 1289 - 1293    DOI : 10.3945/ajcn.2009.28732
Kim KK , Lee KC , Lee JS 2011 Halogranum salarium sp. nov., a halophilic archaeon isolated from sea salt. Syst. Appl. Microbiol. 34 576 - 580    DOI : 10.1016/j.syapm.2011.03.007
Kobayashi T , Okuzumi M , Fujii T 1995 Microflora of fermented puffer fish ovaries in rice-bran “fugunoko nukazuke”. Fish. Sci. 61 291 -
Ley RE , Backhed F , Turnbaugh P , Lozupone CA , Knight RD , Gordon JI 2005 Obesity alters gut microbial ecology. Proc. Natl. Acad. Sci. USA . 102 11070 - 11075    DOI : 10.1073/pnas.0504978102
Li CL , Liu DL , Jiang YT , Zhou YB , Zhang MZ , Jiang W 2009 Prevalence and molecular diversity of Archaea in subgingival pockets of periodontitis patients. Oral Microbiol. Immunol. 24 343 - 346    DOI : 10.1111/j.1399-302X.2009.00514.x
Minegishi H , Echigo A , Nagaoka S , Kamekura M , Usami R 2010 Halarchaeum acidiphilum gen. nov., sp. nov., a moderately acidophilic haloarchaeon isolated from commercial solar salt. Int. J. Syst. Evol. Microbiol. 60 2513 - 2516    DOI : 10.1099/ijs.0.013722-0
Minegishi H , Echigo A , Shimane Y , Kamekura M , Tanasupawat S , Visessanguan W , Usami R 2012 Halobacterium piscisalsi Yachai et al. 2008 is a subjective junior synonym of Halobacterium salinarum Elazari-Volcani 1957. Int. J. Syst. Evol. Microbiol. 62 2160 - 2162    DOI : 10.1099/ijs.0.036905-0
Na J , Kang M , Kim J , Jin Y , Je J , Kim J 2011 Distribution and identification of halophilic bacteria in solar salts produced during entire manufacturing process. Kor. J. Microbiol. Biotechnol. 39 133 - 139
Nagaoka S , Minegishi H , Echigo A , Shimane Y , Kamekura M , Usami R 2011 Halostagnicola alkaliphila sp. nov., an alkaliphilic haloarchaeon from commercial rock salt. Int. J. Syst. Evol. Microbiol. 61 1149 - 1152    DOI : 10.1099/ijs.0.023119-0
Nam YD , Chang HW , Kim KH , Roh SW , Kim MS , Jung MJ 2008 Bacterial, archaeal, and eukaryal diversity in the intestines of Korean people. J. Microbiol. 46 491 - 501    DOI : 10.1007/s12275-008-0199-7
Namwong S , Tanasupawat S , Kudo T , Itoh T 2011 Haloarcula salaria sp. nov. and Haloarcula tradensis sp. nov., isolated from salt in Thai fish sauce. Int. J. Syst. Evol. Microbiol. 61 231 - 236    DOI : 10.1099/ijs.0.021790-0
Namwong S , Tanasupawat S , Visessanguan W , Kudo T , Itoh T 2077 Halococcus thailandensis sp. nov., from fish sauce in Thailand. Int. J. Syst. Evol. Microbiol. 57 2199 - 2203    DOI : 10.1099/ijs.0.65218-0
Nicolaus B , Kambourova M , Oner ET 2010 Exopolysaccharides from extremophiles: from fundamentals to biotechnology. Environ. Technol. 31 1145 - 1158    DOI : 10.1080/09593330903552094
Oren A 2012 Taxonomy of the family Halobacteriaceae: a paradigm for changing concepts in prokaryote systematics. Int. J. Syst. Evol. Microbiol. 62 263 - 271    DOI : 10.1099/ijs.0.038653-0
Oxley AP , Lanfranconi MP , Wurdemann D , Ott S , Schreiber S , McGenity TJ 2010 Halophilic archaea in the human intestinal mucosa. Environ. Microbiol. 12 2398 - 2410    DOI : 10.1111/j.1462-2920.2010.02212.x
Park EJ , Chang HW , Kim KH , Nam YD , Roh SW , Bae JW 2009 Application of quantitative real-time PCR for enumeration of total bacterial, archaeal, and yeast populations in kimchi. J. Microbiol. 47 682 - 685    DOI : 10.1007/s12275-009-0297-1
Parolis H , Parolis LAS , Boan IF , Rodriguez-Valera F , Widmalm G , Manca MC 1996 The structure of the exopolysaccharide produced by the halophilic archaeon Haloferax mediterranei strain R4 (ATCC 33500). Carbohydr. Res. 295 147 - 156    DOI : 10.1016/S0008-6215(96)90134-2
Price LB , Shand RF 2000 Halocin S8: a 36-amino-acid microhalocin from the haloarchaeal strain S8a. J. Bacteriol. 182 4951 - 4958    DOI : 10.1128/JB.182.17.4951-4958.2000
Purdy KJ , Cresswell-Maynard TD , Nedwell DB , McGenity TJ , Grant WD , Timmis KN 2004 Isolation of haloarchaea that grow at low salinities. Environ. Microbiol. 6 591 - 595    DOI : 10.1111/j.1462-2920.2004.00592.x
Quillaguamán J , Guzmán H , Van-Thuoc D , Hatti-Kaul R 2010 Synthesis and production of polyhydroxyalkanoates by halophiles: current potential and future prospects. Appl. Microbiol. Biotechnol. 85 1687 - 1696    DOI : 10.1007/s00253-009-2397-6
Roh SW , Bae JW 2009 Halorubrum cibi sp. nov., an extremely halophilic archaeon from salt-fermented seafood. J. Microbiol. 47 162 - 166    DOI : 10.1007/s12275-009-0016-y
Roh SW , Kim KH , Nam YD , Chang HW , Park EJ , Bae JW. 2010 Investigation of archaeal and bacterial diversity in fermented seafood using barcoded pyrosequencing. ISME J. 4 1 - 16    DOI : 10.1038/ismej.2009.83
Roh SW , Lee ML , Bae JW 2010 Haladaptatus cibarius sp. nov., an extremely halophilic archaeon from seafood, and emended description of the genus Haladaptatus. Int. J. Syst. Evol. Microbiol. 60 1187 - 1190    DOI : 10.1099/ijs.0.013037-0
Roh SW , Nam YD , Chang HW , Kim KH , Sung Y , Kim MS 2009 Haloterrigena jeotgali sp. nov., an extremely halophilic archaeon from salt-fermented food. Int. J. Syst. Evol. Microbiol. 59 2359 - 2363    DOI : 10.1099/ijs.0.008243-0
Roh SW , Nam YD , Chang HW , Sung Y , Kim KH , Lee HJ 2007 Natronococcus jeotgali sp. nov., a halophilic archaeon isolated from shrimp jeotgal, a traditional fermented seafood from Korea. Int. J. Syst. Evol. Microbiol. 57 2129 - 2131    DOI : 10.1099/ijs.0.65120-0
Roh SW , Nam YD , Chang HW , Sung Y , Kim KH , Oh HM 2007 Halalkalicoccus jeotgali sp. nov., a halophilic archaeon from shrimp jeotgal, a traditional Korean fermented seafood. Int. J. Syst. Evol. Microbiol. 57 2296 - 2298    DOI : 10.1099/ijs.0.65121-0
Ryu K , Kim J , Dordick JS 1994 Catalytic prop erties and potential of an extracellular protease from an extreme halophile. Enzyme Microb. Technol. 16 266 - 275    DOI : 10.1016/0141-0229(94)90165-1
Samuel BS , Hansen EE , Manchester JK , Coutinho PM , Henrissat B , Fulton R 2007 Genomic and metabolic adaptations of Methanobrevibacter smithii to the human gut. Proc. Natl. Acad. Sci. USA. 104 10643 - 10648    DOI : 10.1073/pnas.0704189104
Savage KN , Krumholz LR , Oren A , Elshahed MS 2007 Haladaptatus paucihalophilus gen. nov., sp. nov., a halophilic archaeon isolated from a low-salt, sulfide-rich spring. Int. J. Syst. Evol. Microbiol. 57 19 - 24    DOI : 10.1099/ijs.0.64464-0
Schmitt W , Rdest U , Goebel W 1990 Efficient high-performance liquid chromatographic system for the purification of a halobacterial serine protease. J. Chromatogr. 521 211 - 220    DOI : 10.1016/0021-9673(90)85045-W
Shi W , Tang X , Huang Y , Gan F , Tang B , Shen P 2006 An extracellular halophilic protease SptA from a halophilic archaeon Natrinema sp. J7: gene cloning, expression and characterization. Extremophiles 10 599 - 606    DOI : 10.1007/s00792-006-0003-8
Shimane Y , Hatada Y , Minegishi H , Echigo A , Nagaoka S , Miyazaki M 2011 Salarchaeum japonicum gen. nov., sp. nov., an aerobic, extremely halophilic member of the archaea isolated from commercial salt. Int. J. Syst. Evol. Microbiol. 61 2266 - 2270    DOI : 10.1099/ijs.0.025064-0
Shimane Y , Hatada Y , Minegishi H , Mizuki T , Echigo A , Miyazaki M 2010 Natronoarchaeum mannanilyticum gen. nov., sp. nov., an aerobic, extremely halophilic archaeon isolated from commercial salt. Int. J. Syst. Evol. Microbiol. 60 2529 - 2534    DOI : 10.1099/ijs.0.016600-0
Shimoshige H , Yamada T , Minegishi H , Echigo A , Shimane Y , Kamekura M 2012 Halobaculum magnesiiphilum sp. nov., a magnesium dependent haloarchaeon, capable of growth in 1% (w/v) NaCl, isolated from commercial salt. Int. J. Syst. Evol. Microbiol. 63 861 - 866    DOI : 10.1099/ijs.0.037432-0
Stepanov VM , Rudenskaya GN , Revina LP , Gryaznova YB , Lysogorskaya EN , Filippova IYu 1992 A serine proteinase of an archaebacterium, Halobacterium mediterranei. A homologue of eubacterial subtilisins. Biochem. J. 285 281 - 286
Studdert CA , Herrera Seitz MK , Plasencia Gil MI , Sanchez JJ , de Castro RE 2001 Purification and biochemical characterization of the haloalkaliphilic archaeon Natronococcus occultus extracellular serine protease. J. Basic Microbiol. 41 375 - 383
Sun C , Li Y , Mei S , Lu Q , Zhou L , Xiang H 2005 A single gene directs both production and immunity of halocin C8 in a haloarchaeal strain AS7092. Mol. Microbiol. 57 537 - 549    DOI : 10.1111/j.1365-2958.2005.04705.x
Tapingkae W , Tanasupawat S , Itoh T , Parkin KL , Benjakul S , Visessanguan W 2008 Natrinema gari sp. nov., a halophilic archaeon isolated from fish sauce in Thailand. Int. J. Syst. Evol. Microbiol. 58 2378 - 2383    DOI : 10.1099/ijs.0.65644-0
Tapingkae W , Tanasupawat S , Parkin KL , Benjakul S , Visessanguan W 2010 Degradation of histamine by extremely halophilic archaea isolated from high salt-fermented fishery products. Enzyme Microb. Technol. 46 92 - 99    DOI : 10.1016/j.enzmictec.2009.10.011
Vidyasagar M , Prakash S , Litchfield C , Sreeramulu K. 2006 Purification and characterization of a thermostable, haloalkaliphilic extracellular serine protease from the extreme halophilic archaeon Halogeometricum borinquense strain TSS101. Archaea 2 51 - 57    DOI : 10.1155/2006/430763
Vitali B , Ndagijimana M , Cruciani F , Carnevali P , Candela M , Guerzoni ME 2010 Impact of a synbiotic food on the gut microbial ecology and metabolic profiles. BMC Microbiol. 10 4 -    DOI : 10.1186/1471-2180-10-4
Woese CR , Kandler O , Wheelis ML 1990 Towards a natural system of organisms: proposal for the domains Archaea, Bacteria, and Eucarya. Proc. Natl. Acad. Sci. USA 87 4576 - 4579    DOI : 10.1073/pnas.87.12.4576
Yachai M , Tanasupawat S , Itoh T , Benjakul S , Visessanguan W , Valyasevi R 2008 Halobacterium piscisalsi sp. nov., from fermented fish (pla-ra) in Thailand. Int. J. Syst. Evol. Microbiol. 58 2136 - 2140    DOI : 10.1099/ijs.0.65592-0