review : Role of intestinal microflora in xenobiotic-induced toxicity

( Hye Gwang Jeong ),( Mi Jeong Kang ),( Hyung Gyun Kim ),( Do Gyeong Oh ),( Jin Sung Kim ),( Sang Kyu Lee ),( Tae Cheon Jeong ) 영남대학교 약품개발연구소 2013 영남대학교 약품개발연구소 연구업적집 Vol.23 No.0

In addition to its role in digestion of food in the gastrointestinal tract, the intestinal microflora is also capable of biotransforming numerous drugs. Likewise, the intestinal microflora may significantly modulate xenobiotic-induced toxicity by either activating or inactivating xenobiotics via metabolism. To date, most investigations of xenobiotic metabolism have focused not only on metabolism in host tissues, but the modulation of the pharmacological activity of drugs by the intestinal microflora. Despite its importance, the presumed role of intestinal microflora metabolism inxenobiotic-induced toxicity has been understudied. Therefore, it is appropriate to briefly review our current situation, and state which research in xenobiotic metabolism by intestinal microflora, particularly in the field of toxicology, is needed.

Aqueous Extract of Lysimachia christinae Hance Prevents Cholesterol Gallstone in Mice by Affecting the Intestinal Microflora

( Shijia Liu ),( Quji Luorong ),( Kaizhi Hu ),( Weiguo Cao ),( Wei Tao ),( Handeng Liu ),( Dan Zhang ) 한국미생물 · 생명공학회 2021 Journal of microbiology and biotechnology Vol.31 No.9

With changes in human dietary patterns, the proportion of high-fat and high-cholesterol foods in the daily diet has increased. As a result, the incidence rate of cholelithiasis is increasing rapidly. Many studies have reported on the crucial role that the intestinal microflora plays in the progression of gallstones. Although the whole herb of Lysimachia christinae, a traditional Chinese medicine, has long been extensively used as a remedy for cholelithiasis in China, its effects on the intestinal microflora remain unknown. Hence, in this study, we investigated the ability of the aqueous extract of L. christinae (LAE) to prevent cholesterol gallstones (CGSs) in model animals by affecting the intestinal microflora. The effects of LAE on body weight, serum lipid profile, visceral organ indexes, and histomorphology were studied in male C57BL/6J mice, which were induced by a lithogenic diet. After the 8-week study, CGSs formation was greatly reduced after LAE treatment. LAE also reduced body weight gain and hyperlipidemia and restored the histomorphological changes. Moreover, the intestinal microflora exhibited significant variation. In the model group fed the lithogenic diet, the abundances of the genera unclassified Porphyromonadaceae, Lactobacillus and Alloprevotella decreased, but in contrast, Akkermansia dramatically increased compared with the control check group, which was fed a normal diet; the administration of LAE reversed these changes. These results imply that L. christinae can be considered an efficient therapy for eliminating CGSs induced by a high-fat and high-cholesterol diet, which may be achieved by influencing the intestinal microflora.

Inhibitory Effects of Bifidobacterium spp. Isolated from a Healthy Korean on Harmful Enzymes of Human Intestinal Microflora

Park, Hye-Young,Bae, Eun-Ah,Han, Myung-Joo,Choi, Eung-Chil,Kim, Dong-Hyun The Pharmaceutical Society of Korea 1998 Archives of Pharmacal Research Vol.21 No.1

Five hundreds of bifidobacteria were isolated from a healthy Korean and the inhibitory effects of these isloated bacteria on harmful enzymes of human intestinal microflora were examined by cocultivation of the isolated bifidobacteria with E. coli or total human intestinal microflora. In comparison with the results of E. coli or intestinal microflora cultivation, Bifidobacterium breve K-110, B. breve K-111 and B. infantis K-525 effectively inhibited harmful enzymes ($\beta$-glucuronidase and tryptophanase) of E. coli and lowered the pH of the culture media. Also they inhibited the harmful enzymes ($\beta$-glucosidase, $\beta$-glucuronidase, tryptophanase and urease) and ammonia production of intestinal microflora, and lowered pH of the culture media by increasing lactic acid bacteria of intestinal microflora. When these isolated bifidobacteria were administered on mice, fecal harmful enzymes were also inhibited. Among tested bifidobacteria, B. breve K-110 had the highest inhibitory effect of fecal harmful enzymes.

Biotransformation of Panax ginseng extract by rat intestinal microflora: identification and quantification of metabolites using liquid chromatography-tandem mass spectrometry

Dong, Wei-Wei,Zhao, Jinhua,Zhong, Fei-Liang,Zhu, Wen-Jing,Jiang, Jun,Wu, Songquan,Yang, Deok-Chun,Li, Donghao,Quan, Lin-Hu The Korean Society of Ginseng 2017 Journal of Ginseng Research Vol.41 No.4

Background: In general, after Panax ginseng is administered orally, intestinal microbes play a crucial role in its degradation and metabolization process. Studies on the metabolism of P. ginseng by microflora are important for obtaining a better understanding of their biological effects. Methods: In vitro biotransformation of P. ginseng extract by rat intestinal microflora was investigated at $37^{\circ}C$ for 24 h, and the simultaneous determination of the metabolites and metabolic profile of P. ginseng saponins by rat intestinal microflora was achieved using LC-MS/MS. Results: A total of seven ginsenosides were detected in the P. ginseng extract, including ginsenosides Rg1, Re, Rf, Rb1, Rc, Rb2, and Rd. In the transformed P. ginseng samples, considerable amounts of deglycosylated metabolite compound K and Rh1 were detected. In addition, minimal amounts of deglycosylated metabolites (ginsenosides Rg2, F1, F2, Rg3, and protopanaxatriol-type ginsenosides) and untransformed ginsenosides Re, Rg1, and Rd were detected at 24 h. The results indicated that the primary metabolites are compound K and Rh1, and the protopanaxadiol-type ginsenosides were more easily metabolized than protopanaxatriol-type ginsenosides. Conclusion: This is the first report of the identification and quantification of the metabolism and metabolic profile of P. ginseng extract in rat intestinal microflora using LC-MS/MS. The current study provided new insights for studying the metabolism and active metabolites of P. ginseng.

In vitro 및 In vivo에서 인진쑥 추출물이 장내미생물에 미치는 영향

오미현(Mi Hyun Oh),김광엽(Kwang Yup Kim) 한국식품영양과학회 2010 한국식품영양과학회지 Vol.39 No.11

본 실험은 인진쑥의 용매 분획물에 대하여 항균활성을 검색하였다. 이에 따라 가장 항균활성이 좋은 인진쑥의 클로로포름 분획물을 가지고 항균활성실험을 진행하였고, 기능성물질인 페놀류의 함량 정도에 따라 항균활성을 보여주는 지에 대하여 총 폴리페놀과 총 플라보노이드 함량을 분석하였고, in vivo 실험을 통하여 장내미생물 균총의 변화를 확인하였다. 인진쑥 에탄올 추출물을 헥산, 클로로포름, 에틸아세테이트, 부탄올로 분획하여 용매 분획물을 가지고 항균활성을 검색한 결과, paper disc agar diffusion법에서 장내유해균인 C. perfringens, C. difficile, E. limosum 및 B. fragilis 모두가 다른 용매 분획물들에 비해 클로로포름 분획물에서 생육 억제환의 크기가 가장 크게 생성되었다. 장내유익균인 B. bifidum, L. acidophilus는 인진쑥의 헥산, 클로로포름, 에틸아세테이트, 부탄올, 물 분획물에서 억제환이 생성되지 않은 결과를 보여주었다. 동물실험 결과, 인진쑥 추출물은 일반식이군에 비하여 비만식이군에서 장내유해균을 억제하고 장내 유익균을 증진시키는 결과를 보여주었다. 상기 결과들을 종합해 볼 때, 인진쑥 추출물은 장내 유해균은 억제시키고, 장내 유익균은 증식시키거나 별다른 영향을 주지 않는 결과, 인체 장내 균총 조성을 바람직한 방향으로 개선시켜 장내 기능을 향상시킬 수 있을 것으로 기대되고 인진쑥 추출물의 장내유해세균에 대한 항균효과를 확인함으로써 장내균총 개선을 위한 기능성식품으로 활용할 가치가 있는 것으로 사료된다. This study was designed to investigate the effect of Artemisia capillaris extracts on the intestinal microflora. In agar diffusion method, the solvent fractions of Artemisia capillaris showed growth inhibition against the intestinal microflora. In particular, the chloroform fraction of Artemisia capillaris had strong antibacterial activity against Clostridium perfringens, Clostridium difficile, Eubacterium limosum, and Bacteroides fragilis, but did not show antibacterial activity against Bifidobacterium bifidum and Lactobacillus acidophilus. Most chloroform fraction of Artemisia capillaris inhibitory activities were not reduced by heat treatment or pH variation against C. perfringens, C. difficile, E. limosum, and B. fragilis. MICs of the chloroform fraction were 1.25 ㎎/mL against C. perfringens, E. limosum and B. fragilis and 2.5 ㎎/mL against C. difficile. MBCs of chloroform fraction were 5 ㎎/mL against C. perfringens, E. limosum and 2.5 ㎎/mL against C. difficile, B. fragilis. The ethyl acetate fraction of Artemisia capillaris showed 3.08±0.03 ㎎/10 ㎎ total polyphenol and 1.91±0.03 ㎎/10 ㎎ total flavonoid contents. In vivo tests were performed to investigate the influence of Artemisia capillaris extract on the intestinal microflora in rats. The results showed the possibilities of utilizing Artemisia capillaris extracts as a functional food component to control intestinal microflora.

Metabolism of Ginsenosides to Bioactive Compounds by Intestinal Microflora and Its Industrial Application

Dong-Hyun Kim 고려인삼학회 2009 Journal of Ginseng Research Vol.33 No.3

Korean ginseng, which contains ginsenosides and polysaccharides as its main constituents, is orally administered to humans. Ginsenosides and polysaccharides are not easily absorbed by the body through the intestines due to their hydrophilicity. Therefore, these constituents which include ginsenosides Rb1, Rb2, and Rc, inevitably come into contact with intestinal microflora in the alimentary tract and can be metabolized by intestinal microflora. Since most of the metabolites such as compound K and protopanaxatriol are nonpolar compared to the parental components, these metabolites are easily absorbed from the gastrointestinal tract. The absorbed metabolites may express pharmacological actions, such as antitumor, antidiabetic, anti-inflammatory, anti-allergic, and neuroprotective effects. However, the activities that metabolize these constituents to bioactive compounds differ significantly between individuals because all individuals possess characteristic indigenous strains of intestinal bacteria. Recently, ginseng has been fermented with enzymes or microbes to develop ginsengs that contain these metabolites. However, before using these enzymes and probiotics, their safety and biotransforming activity should be assessed. Intestinal microflora play an important role in the pharmacological action of orally administered ginseng.

Metabolism of Ginsenosides to Bioactive Compounds by Intestinal Microflora and Its Industrial Application

Kim, Dong-Hyun The Korean Society of Ginseng 2009 Journal of Ginseng Research Vol.33 No.3

Korean ginseng, which contains ginsenosides and polysaccharides as its main constituents, is orally administered to humans. Ginsenosides and polysaccharides are not easily absorbed by the body through the intestines due to their hydrophilicity. Therefore, these constituents which include ginsenosides Rb1, Rb2, and Rc, inevitably come into contact with intestinal microflora in the alimentary tract and can be metabolized by intestinal microflora. Since most of the metabolites such as compound K and protopanaxatriol are nonpolar compared to the parental components, these metabolites are easily absorbed from the gastrointestinal tract. The absorbed metabolites may express pharmacological actions, such as antitumor, antidiabetic, anti-inflammatory, anti-allergic, and neuroprotective effects. However, the activities that metabolize these constituents to bioactive compounds differ significantly between individuals because all individuals possess characteristic indigenous strains of intestinal bacteria. Recently, ginseng has been fermented with enzymes or microbes to develop ginsengs that contain these metabolites. However, before using these enzymes and probiotics, their safety and biotransforming activity should be assessed. Intestinal microflora play an important role in the pharmacological action of orally administered ginseng.

노화 흰쥐의 장 내 균총 조성에 대한 식이섬유질원의 영향

강어진,양차범,신현경 한국식품영양학회 1998 韓國食品營養學會誌 Vol.11 No.4

한국인이 섭취하는 식이섬유질원중 장내 균총의 개선에 효과가 있을 것이라고 탐색된 사과, 머위, 미역, 쑥을 건조분말화하여 식이섬유의 함량이 식이량의 5%와 15%가 되도록 첨가시켜 제조한 식이를 12개월된 노화쥐에 4주간 급여한 후, 이들의 대장내용물로부터 총균수와 주요 장내미생물의 생균수를 측정하였다. 노화쥐에서 4종류의 식이섬유질원을 섭취시킨 결과 총균수와 Bifidobacterium, Lactobacillus의 수는 각 실험군간에 유의적인 차이를 보여주지 못했으나 장내 우세균중 Peptococcaceae는 사과 5% 시험군이 타실험군에 비해 유의적으로 많은 경향을 보였고, Streptococcus는 쑥 15% 섭취군에서만 타실험군에 비해 유의적으로 적은 경향을 보였다. 일반적으로 쥐에게는 나타나지 않는다고 보고되었던 Cl. perfringens가 노화가 진행된 흰쥐에게 나타났으며 Clostridium속균은 사과 5%에서 유의적으로 많은 경향을 보였다. 5% 식이섬유 첨가군이 15% 첨가군에 비해 유의적으로 많은 경향을 보였다. Staphylococcus는 섬유질원이 첨가된 모든 실험군들이 셀룰로즈 첨가군보다 더 적은 경향을 보였다. 이들 결과를 종합해 보면 본 실험에 사용된 실험군에서 쑥 15% 섭취군이 장내 균총 개선의 측면에서 효과적인 식이섬유질원으로 판단된다. This study was performed to investigate the influence of various dietary fiber sources such as mugwort, apple, sea mustard, butterbur on the intestinal microflora in aged rats. Nine groups of aged rats (12months after weanling) were fed each experimental diet containing 5% and 15% dietary fibers for 4 weeks. The contents in large intestine of aged rats used for the measurement of intestinal microflora. Total viable counts and numbers of Bifidobacterium, Lactobacillus, Clostridium, E. coli and Staphylococcus were determined by nonselective medium and various selective media. The intake of dietary fiber sources employed did not show any difference in the number of total microorganisms, Lactobacillus and Bifidobacterium. It was remarkable that Clostridium perfringens appeared in the colon of aged rats. The populations of Peptococcus and Clostridium were significantly larger in the apple 5% group than in other dietary fiber groups while the number of Staphylococcus was significantly smaller in the dietary fiber groups than in cellulose groups. And the Streptococcus populations decreased in the mugwort 15% group. Accordingly, the mugwort 15% group is effective in improving intestinal flora of aged rats.

장내 미생물 개선효과가 있는 약용식물소재 탐색

조인숙,한영희,이지영,박경열 韓國藥用作物學會 2007 한국약용작물학회지 Vol.15 No.1

장내미생물 개선에 효과가 있는 약용식물소재들을 탐색하여 정장제품 개발하고자 13종의 식물을 물과 에탄올로 각각 추출하여 농도별로 유해균인 C. perfringens, E. coli와 유익균인 B. longum의 생육에 미치는 영향을 in vitro실험으로 시험한 결과는 아래와 같다. 가. C. perfringens은 민들레와 인진쑥 물 추출물에, 돌나물, 오미자, 민들레, 부추, 생강, 쑥, 인진쑥, 질경이 에탄올추출물에 강하게 생육억제 되었다. 나. E. coli은 돌나물, 오미자 물과 에탄올 추출물에서 강하게 생육억제 되었다. 다. B. longum은 추출용매에 관계없이 생육에는 크게 영향을 주지 않았다. 라. 돌나물과 오미자 에탄올추출물이 유익균에 생육억제 없이, 두 유해균을 억제됨으로서 이들 소재가 정장제품으로의 개발 가능성이 있다고 생각되었다. Extracts of 13 medicinal plants were tested to investigate the improvable effects on microflora growth in the intestines of human. Water extracts of Artemisia capillaris, Taraxacum platycarpum and Ethanol extracts of Allium tuberosum, Artemisia capillaris, Artemisia vulgaris, Plantago asiatica, Schizandra chinensis, Sedum sarmentosum, Taraxacum platycarpum, Zingiber officinale inhibited the growth of C. perfringens. Water and ethanol extracts of Sedum sarmentosum, Schizandra chinensis inhibited the growth of E. coli. While 13 medicinal plants were not remarkably inhibited the growth of B. longum. Therefore, ethanol extracts of Schizandra chinensis, Sedum sarmentosum can be utilized as functional food materials to improve in the intestines.

선인장 추출물이 인체 장내미생물에 미치는 영향

라보현,이운종,조윤원,김광엽 경상대학교 농업생명과학연구원 2009 농업생명과학연구 Vol.43 No.3

This study was designed to investigate the effect of cactus (Opuntia ficus-indica var. saboten) extracts on the intestinal bacteria, antioxidative activity and angiotensin -I- converting enzyme(ACE) inhibitory activity. The antimicrobial activities were measured using the 96well-plate method and disc plate method with concentration of 20mg of cactus extract. The stem extract of cactus was inhibitory against Eubacterium limosum, Clostridium perfringens, C. butyricum, C. difficile and Staphylococcus aureus, but was not inhibitory against Bacteroides fragilis, Bifidobacterium bifidum, Lactobacillus acidophilis, Streptococcus thermophilus. The fruit extract of cactus showed no inhibition against Bacteroides fragilis, Bifidobacterium bifidum, Lactobacillus acidophilis, and Streptococcus thermophilis. Their inhibitory activities were not reduced after heat and pH treatment. Antioxidative effects of cactus extracts showed high total polyphenol and flavonoid contents and high activity against free radical DPPH. The stem and fruit extract of cactus showed strong ACE inhibitory activities of 88.8% and 69.2%, respectively. In conclusion cactus (Opuntia ficus-indica var. saboten) extract might be utilized as a functional food material to control intestinal microflora. 본 연구에서는 인체 내 장내 세균 및 병원성 식중독 세균에 선인장 추출물이 미치는 영향과 항산화, 항고혈압 활성에 대하여 분석하였다. 항균활성은 96well- plate법과 paper disc법을 이용하여 실험하였으며 줄기 추출물의 경우 96well-plate 및 paper disc법의 결과, 장내유해균인 Eubacterium limosum 및 Clostridium perfringens, C. butyricum, C. difficile과 Staphylococcus aureus에 대하여 높은 억제율을 보였으나 Bacteroides fragilis, Bifidobacterium bifidum, Lactobacillus acidophilis, Streptococcus thermophilus의 경우 억제율을 나타내지 않았다. 열매 추출물의 경우 장내유해균 및 장내유익균에 Bacteroides fragilis, Bifidobacterium bifidum, Lactobacillus acidophilis, and Streptococcus thermophilis에 대하여 억제율을 나타내지 않았다. 또한 줄기 추출물의 경우 열 및 pH에서도 장내미생물에 대한 항균활성에 안정함을 나타내었다. 선인장 추출물의 폴리페놀과 플라보노이드 함량 및 DPPH 전자공여능을 측정한 결과 열처리하지 않은 열매와 줄기 추출물의 폴리페놀은 3.02 mg/g, 5.85 mg/g, 플라보노이드는 1.04 mg/g, 2.1 mg/g, 전자공여능은 87, 88%로 높은 수율을 나타내었다. 선인장 추출물의 항고혈압활성은 줄기 추출물의 경우 88.8% 열매 추출물의 경우 69.2%의 항고혈압활성을 보였으며 상기 결과를 종합할 때, 선인장 줄기추출물은 장내 유해균의 억제 및 유익균의 증진을 통한 장내 균총 개선을 위한 기능성 식품소재로 활용할 수 있다고 판단된다.