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Leaky Gut Cure

Leaky Gut Cure by Karen Brimeyer teaches sufferers all around the world that healthy foods can be harmful for people who already developed leaking gut. In the main guide, the author uncovers some keys to leaky gut cure diet. When it comes to healing foods for your digestive tract, the author recommends people that they should not overlook bone broth, raw cultured dairy, fermented vegetables, coconut products, super seeds. In addition to healing foods, people also add 5 essential supplements to their daily diet plan, which are L-glutamine, Digestive enzymes, Aloe VeraLicorice Root, and Probiotics. This system also provides people with different meditation techniques, sleep improving tips, and some easy-to-follow exercises to boost the healing process quickly. Especially, the methods this program applies are suitable for most people regardless of the severity of their condition. More here...

Leaky Gut Cure Summary


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I usually find books written on this category hard to understand and full of jargon. But the author was capable of presenting advanced techniques in an extremely easy to understand language.

Overall my first impression of this book is good. I think it was sincerely written and looks to be very helpful.

Role Of The Gastrointestinal Microbiota In Humans

Traditionally, the colon has been considered to largely be the human sewage system which, as well as storing and removing waste material from the GI tract, was capable of recycling water (i.e., absorption). However, we now recognize that the GI tract is one of the most metabolically and immunologically active organs of the human body. Indeed, the primary function of the microbiota is generally considered to be salvage of energy via fermentation of carbohydrates, such as indigestible dietary residues (plant cell walls, non-digestible fibers and oligosaccharides), mucin side-chains and sloughed-off epithelial cells (5,6,8,13,17). It has been estimated that between 20 and 60 grams of carbohydrate are available in the colon of healthy human adults per day, as well as 5-20 grams of protein. In addition to salvaging energy, principally through production of short-chain fatty acids (SCFAs) and their subsequent absorption and use by the host, microbial fermentation produces gases (principally...

Age Altered Aspects of the Intestinal Microbiota

Normal aging is associated with significant changes in the function of most organs and tissues, such as decreased taste thresholds, hypochlorhydria due to atrophic gastritis, and decreased liver blood flow and size (11). The GI tract is no exception, and there is increased evidence of impaired gastrointestinal function with aging (3,11-13). In the GI tract of the elderly, the age-related changes include decreased acid secretion by the gastric mucosa, and greater permeability of mucosal membranes which have been linked to increase in circulating antibodies to components of the intestinal microbiota in elderly subjects. Therefore, certain microbes which can take advantage of new ecological niches are assumed to become predominant inhabitants, leading to a dramatic shift in the composition of the gut microbiota upon age. Although the knowledge about the age-related alteration of the human intestinal microbiota is still limited, the structure of the intestinal microbiota in the healthy...

The Metabolism of Polyphenols by the Human Gut Microbiota

Polyphenols are considered to be key active constituents of fruits and vegetables and responsible for many of the health protective effects of diets rich in these foods. While their structure varies considerably, following ingestion, most ( 95 ) persist to the colon where they encounter the human gut microbiota. Here they may undergo considerable structural alteration to compounds that may have enhanced biological properties or possibly degraded into inert metabolites and excreted. As such, the human gut microbiota may have a significant influence on the final outcomes of polyphenol ingestion. Moreover, interindividual variation in the composition of the microbiota means that certain compounds are metabolized in different ways, and this is reflected in the considerable variability seen in excreted polyphenol metabolites. Consequently, polyphenols as active ingredients in functional foods may turn out to be beneficial for only a certain proportion of the population. Clearly, this may...

Gut Bacterial Involvement in Colorectal Cancer

In animals, the presence of the intestinal microbiota has a major impact on colonic tumor formation (37,38). In a study conducted by Reddy and coworkers (38) the rate of tumor formation was much more rapid in conventional than in germ-free rats treated with the tumor initiator 1,2-dimethylhydrazine (DMH). After 20 weeks, 17 of conventional rats had colon carcinomas, whereas there were no tumors (adenomas or carcinomas) in the germ-free animals. At 40 weeks, two out of 18 germ-free rats had developed benign adenomas (although still none had carcinomas), compared to six out of 24 conventional rats with tumors (4 cancers, 2 adenomas) thus the gut microbiota had a tumor-promoting effect when DHM was the tumor initiator. A high incidence of spontaneous CRC has been demonstrated in the T-cell receptor (TCR) b chain and p53 double-knockout mice. In one study, 70 of the animals with a conventional microbiota developed adenocarcinomas, whereas adenocarcinoma of the colon did not occur in...

Effects of Gut Microbiota on Gene Expression

To date, there are only a few molecular descriptions of how bacteria in the normal microbiota regulate gene products with presumed positive functions in the intestine or systemically. Dramatic changes in gene expression were noted when germ-free mice were mono-colonized with Bacteroides thetaiotaomicron, a component of the normal microbiota of adult mice and humans (64). A number of genes involved in general mechanisms like nutrient uptake, fortification of the intestinal epithelial barrier, postnatal development, and angiogenesis are regulated in response to this commensal microbe. In addition, it is becoming clear that metabolic products, produced by the gut microbiota, can alter gene expression in the colonocyte e.g., butyrate, produced by bacterial fermentation of dietary fiber, induces p21 Cip1 WAF1 mRNA (important in cell cycle control) and secondary bile acids, produced from primary bile acids by the gut microbiota, alter AP-1-dependent and COX-2 gene transcription) (65,66).

Tracking bifidobacteria in human intestinal samples

Demonstrated by culturing from faecal samples on selective medium which indicated levels of between one and ten percent in adults (Harmsen et al., 2000b), and even up to 90 in infants (Harmsen et al., 2000a). However, these conventional plate counts overestimated bifidobacteria counts by 2 to 10 as a result of underestimation of the total microbial counts by culturing (Mitsuoka, 1990). In addition, it is very challenging to obtain pure cultures of the majority of species in the intestinal microbiota due to the largely anaerobic nature of this community and the paucity of suitable enrichment strategies to stimulate intestinal conditions. Less is known about bifidobacterial numbers in other gastrointestinal sites such as the ileum. studies are limited to ileostomy patients in which the microbiota differs from those of the healthy distal ileum and these indicated that bifidobacterial counts varied between 0.1 and 10 of the total microbiota. The number of bacteria in the terminal ileum of...

The Prebiotic Strategy To Modifying The Intestinal Microbiota

For a variety of reasons, the two bacterial genera most often advocated as beneficial organisms with which to augment the intestinal microbiota are lactobacilli and bifidobacteria, both of which are common members of the human intestinal microbiota (11,12). These bacteria are numerically common, non-pathogenic, non-putrefactive, non-toxigenic, saccharolytic organisms that appear from available knowledge to provide little opportunity for deleterious activity in the intestinal tract. As such, they are reasonable candidates to target in terms of restoring a favorable balance of intestinal species. While the probiotic strategy aims to supplement the intestinal microbiota via the ingestion of live bacteria, the prebiotic strategy aims to stimulate the proliferation and or activity of beneficial microbial populations already resident in the intestine. The characteristics shared by all successful prebiotics is that they remain largely undigested during passage through the stomach and small...

Use of Probiotics to Combat Gastrointestinal Infections

Probiotics have been shown to be useful in the treatment of a variety of gastrointestinal disorders, and the details are presented in Table 4. A number of these disorders have a significant inflammatory component in the small and or large intestine and there is a growing body of research to suggest that probiotic bacteria may be useful particularly in many of these pediatric gastrointestinal conditions. Specific strains of Lactobacillus rhamnosus, Lb. reuteri, Lb. plantarum, Bifidobacterium lactis, and Saccharomyces cerevisiae (boulardii) have all been extensively studied. Probiotics can reduce the duration and severity of rotaviral enteritis, as well as decrease the risk of antibiotic-associated diarrhea in children and Clostridium difficile diarrhea in adults. Prevention of viral diarrhea in day-care centers as well as traveler's diarrhea has been demonstrated with some probiotics, although not all are equally effective (67). Small bowel bacterial overgrowth conditions may respond...

Development Of Intestinal Microbiota In Dogs And Cats

Although there is paucity of research data concerning the development of intestinal microbiota of dogs and cats, it can be considered to follow a similar pattern as known for other mammals. Intestinal colonization is a gradual process starting immediately after birth. In newborn puppies and kittens the alimentary canal is sterile but is quickly inhabited by bacteria from birth canal and environment. The dam usually licks the newborn thoroughly thus transferring its own indigenous bacteria to her offspring. Within 24 hours the numbers of bacteria in various parts of the gastrointestinal tract of a newborn puppy are similar to those of an adult dog (2). The indigenous intestinal microbiota is considered an integral part of the host defense mechanisms. It forms a barrier against pathogen colonization and also influences the host's immunological, biochemical, and physiological features (6). Once the microbiota has become established, it is relatively stable. Oral antibiotics may have a...

Modifying The Intestinal Microbiota Pre And Probiotics

First documented studies of dietary manipulation of canine and feline intestinal microbiota date back to the beginning of the twentieth century (71). Today, there is growing interest in modifying their gut microbiota towards what is considered a healthy composition, i.e., increase in LAB and bifidobacteria, and decrease in potential pathogenic bacteria (72). Many commercial pet foods now contain prebiotics (e.g., fructo-oligosaccharides, FOS). In addition, probiotics are also marketed for dogs and cats.

Manipulation of the Gastrointestinal Microbiota by Diet

Dietetic methods can also be used to influence the microecosystem of the intestinal tract in piglets during weaning. At this period important morphological and functional changes occur in the digestive tract of piglets that are also accompanied by changes in the composition of the gut microbiota (17,61). In the first days after weaning Lactobacillus populations decrease considerably whereas the numbers of coliforms increase. In piglets the brush border of the intestinal epithelium can be damaged by feed components (62) or viruses (63) such damage enables enterotoxigenic E. coli to colonize the injured epithelium. Important factors that the piglets had been receiving by maternal milk and that prevented E. coli from colonizing the gut (64) are no more at the animals' disposal. All these changes support the tendency to low weight gain and predispose to the occurrence of the diarrheic syndrome. Several researchers tried to influence the morphological and functional development of pigs...

Manipulation of the Gastrointestinal Microbiota by Application of Probiotic Microorganisms

It is of great importance to influence the intestinal microbiota of calves, piglets and poultry at an early age since this is the period when the danger of diarrhea-accompanied diseases of the digestive tract reaches its maximum. Due to their high morbidity and mortality rates such diseases present an extraordinarily serious health and economic issue. Preventive application of probiotics at an early age helps to optimize the composition of the gut microbiota and has an inhibitory effect upon the pathogens of the digestive tract in the young of farm animals. Preventive application of Lactobacillus casei at a dose of 1.108 germs decreased the counts of enterotoxigenic E. coli O101 K99 adhering to the small intestinal mucosa of gnotobiotic lambs by 99.1 and 76.0 on day 2 and 4 after inoculation, respectively (74). Perdigon and coworkers (75) found the preventive effect of L. casei and yoghurt against Salmonella typhimurium infections in mice to depend on the duration of administration....

Gut Bacterial Metabolism and CRC Risk

The enormous numbers and diversity of the human gut microbiota is reflected in a large and varied metabolic capacity, particularly in relation to xenobiotic biotransformation, carcinogen synthesis and activation. The metabolic activities of the gut microbiota can have wide-ranging implications for the health of the host (42). To date the vast majority of mechanisms whereby bacteria are involved in carcinogenesis involve toxic or protective products of bacterial metabolism. Such metabolic activities include numerous enzymatic reactions and degradation of undigested dietary residues. Diet can substantially modulate these activities by providing a vast array of substrates. A wide range of enzyme activities capable of generating potentially carcinogenic metabolites in the colon are associated with the gut microbiota, including b-glucuronidase, b-glucosidase, nitrate reductase and nitro-reductase. These are usually assayed in fecal suspensions and appear to be present in many bacterial...

Composition Of The Adult Fecal Microbiota Assessed By Molecular Techniques

The development and application of PCR-based methods and probing strategies, which have circumvented cultivation, highlighted the tip-of-the-iceberg scenario that our knowledge of the GI tract microbiota amounted to. The coverage that cultivation studies afforded has been calculated to be as low as 10 , although others suggest it may be as high as 40-58 (15,54-56). Modern cultivation media and incubation conditions enable greater diversity, and therefore coverage, to be recognized. However, many components of the human gut microbiota remain elusive to cultivation in vitro. Molecular strategies also have their limitations, including detection limits and inherent biasing. As such, the overall objective of the study generally determines which assay is most appropriate. In the case of investigations to elucidate the diversity and dynamics of the human gut microbiota, a polyphasic approach is best, allowing thorough analysis at multiple taxonomic levels.

The Uropathogenic Ecoli Strain536

Usually Escherichia coli is a normal inhabitant of the gut flora. Variants of E. coli are able to cause extraintestinal infections e.g. urinary tract infections or newborn meningitis. For the colonization and the infectious processes pathogenic bacteria need several virulence factors. The uropathogenic E. coli strain 536 (O6 K15 H31) was isolated from a patient suffering from acute pyelonephritis and is characterized by the production of certain virulence factors such as a -hemolysin (hly), fimbrial adhesins e.g. type 1, P-related and S fimbriae (fm,prf, sfa), the siderophores enterobactin (ent) and yersiniabactin (ybt)1. In the early 1980s uropathogenic E. coli strains have been shown to contain distinct blocks of DNA carrying closely linked virulence genes so-called pathogenicity islands (PAIs). PAIs are generally characterized as follows these structures are present in the genome of pathogenic isolates but absent from non pathogenic variants. Their G+C content differs from the G+C...

Directed PCR Analysis

Wang and coworkers (66) developed 12 species-specific PCR primer sets to monitor the predominant gut microbiota of humans (Bact. distasonis, Bacteroides thetaiotaomicron, Bact. vulgatus, Bifidobacterium adolescentis, Bifidobacterium longum, Clostridium clostridioforme, E. coli, Eubacterium biforme, Eubacterium limosum, Fuso. prausnitzii, Lactobacillus acidophilus and Pep. productus). During validation of the species-specific PCR assays, the sensitivity of each primer set was examined with DNA extracts from pure cultures. Interestingly, such work demonstrated that PCR sensitivities varied markedly. Following validation of the PCR assays, Wang and coworkers (66) examined the presence of the bacterial species in fecal samples from humans (seven adults and two infants), two BALB c mice, two Fischer rats, two cats, one dog, one rhesus monkey and one rabbit. High titers of Clos. clostridioforme, Fuso. prausnitzii and Pep. productus were detected in all samples examined. High titers of Bact....

Investigations At The Subspecies Level

Taken together, the above-mentioned work clearly demonstrates the value of investigations at the subspecies level, as such studies afford more detailed analysis of the diversity and dynamics of the gut microbiota. Furthermore, such strategies allow the detection of microbial perturbations which are often not evident at the bacterial group, genus or species levels (79).

Syndromic Surveillance Case Studies

Factors, including over-the-counter remedy sales, topical Internet searches, and emergency department cases, can often be early warning signs or diagnostic precursors of an outbreak. The New York City DOH and Mental Hygiene currently operate a syndromic surveillance network in New York City (Heffernan et al., 2004). New York City has established a Water-borne Disease Risk Assessment Program to determine Giardia and Cryptosporidium species levels. This program monitors information on cases presumably linked to tap water consumption, so as to ensure rapid detection of any outbreaks. The database maintains information on gastrointestinal disease, particularly emergency department and nursing home statistics, over-the-counter sales for related medicines, and collections of relevant clinical laboratory tests performed. Detailed monitoring of these factors is expected to accelerate the public health response to a biological agent exposure. Additional examples of syndromic surveillance...

Bacterial interactions

One of the mechanisms by which probiotics may confer a health benefit on the host is the modulation of the intestinal microbiota (Ouwehand et al., 2002b). Accordingly, food supplements such as prebiotics, probiotics and symbiotics are generally developed to improve the population and or the activity of lactobacilli and bifidobacteria within the gut microbiota. One of the most promising properties of dairy propionibacteria, in this context, is their bifidogenic effect. Some strains of P. freudenreichii were shown to enhance the growth of bifidobacteria in vitro and their population in the gut. In this respect, propionibacterial metabolites would best fit to the first definition of probiotics being 'growth promoting factors produced by microorganisms' (Lilly and Stillwell, 1965). The best and first recognised effect of probiotics is the alleviation of lactose intolerance by lactic acid bacteria, mainly Streptococcus thermophilus and Lactobacillus bulgaricus used as yoghurt starters. The...

In Situ Profiling Of Transcription In The Gi Tract

Fucose and coordinates the decision to generate a signal for production of host fucosylated glycans when environmental fucose is limited or to induce expression of the bacteria's fucose utilization operon when fucose is abundant (68). Additional studies have evaluated the global intestinal response to colonization of gnotobiotic mice with B. thetaiotaomicron. This colonization dramatically affected the host's gene expression, including several important intestinal functions such as nutrient absorption, mucosal barrier fortification, and postnatal intestinal maturation (9). From the in situ global transcription profiles mentioned above and follow-up experiments it could be established that the production of a previously uncharacterized angiogenin is induced when gnotobiotic mice are colonized with B. thetaiotaomicron, revealing a mechanism whereby intestinal commensal bacteria influence GI-tract bacterial ecology and shape innate immunity (69). In addition, the cellular origin of the...

Reflection of Atopic Genotype

Incomplete knowledge of the genetic characteristics of allergic diseases restricts the full understanding of their possible influence on the development of gut microbiota (58). Theoretically, microbial colonization could be directly affected for example if the atopic genotype was associated with receptor expression on epithelial cells or production of intestinal mucus. There is some indication that the atopic genotype is associated with Figure 2 Mechanisms by which specific components of intestinal microbiota may protect from allergic sensitization and or alleviate symptoms. Adequate microbial composition may reduce allergen uptake by providing maturational stimulus for gut barrier function, enhancing allergen degradation by production of digestive enzymes (this may also reduce allergen allergenicity), improving mucosal integrity by direct exclusion of pathogens that may cause epithelial damage or by enhancing secretory IgA (sIgA) production (possibly via inducing TGF-b secretion) and...

Apicomplexans and their plastids

The clade Apicomplexa is comprised of unicellular eukaryotic protists characterized by an apical complex (Perkins et al. 2000). All of the estimated 5000 species of Apicomplexa are parasitic. The most notable members of the group include Plasmodium falciparum, the causative agent of human malaria, a disease that causes 2 to 3 million deaths annually Cryptosporidium parvum, a significant AIDS-related pathogen that was responsible for more than 400 000 cases of gastrointestinal disease in Milwaukee 1993 (MacKenzie et al. 1995) Toxoplasma gondii a significant agent of morbidity and mortality, particularly among immunosuppressed individuals

Reflection of Environmental Factors

Amongst the best examples of factors which have been clearly shown to influence the development of the gut microbiota and have also been implicated in allergic diseases include the mode of delivery and breast-feeding (116-123). Indeed, it is plausible that the characteristics of fecal microbiota associated with atopic eczema and allergic sensitization may partly reflect dietary factors. It is well known that changes in diet may dramatically affect the microbial composition of the gut. Then again, in allergic infants the diet can reflect the child's health status due to food restrictions. In 39-63 of all infants and young children, atopic eczema is triggered by one or more challenge-confirmed food allergies (124-126). Moreover, the development of manifestations of allergic diseases in children correlates with differences in the composition and immunological characteristics of breast-milk, which on the other hand are affected by maternal gut microbiota and atopy (127-133). For example,...

The Role Of The Enteric Microbiota In The Normal

Underpinning the probiotic concept is the importance of the normal intestinal microbiota in health and disease (12). Establishment of gut microbiota begins within minutes of delivery of the newborn (13,14). During delivery the infant is exposed to bacteria in the birth canal, the environment, maternal fecal microbiota, and other sources (15). The gut is initially colonized by facultative anaerobes such as Escherichia coli and Enterococcus species, possibly due to the absence of anaerobic conditions in the intestine (16). Colonization with bifidobacteria follows, particularly in breast-fed infants, and as the environment becomes more anaerobic, Bacteroides and Clostridia. The importance of the intestinal microbiota is suggested by the fact that the healthy adult gastrointestinal tract is home to a gut microbiota comprising over 400 different species with more bacterial cells in the gut than eucaryotic cells in the human body and with the average mass of bacteria being 1-2 kg. Commensal...

Efficacy Of Probiotics In Inflammatory Bowel Disease Probiotics in Animal Models of IBD

The model of IL-10 knockout mice develop colitis when colonized with normal enteric microbiota but remain disease-free if kept in germ-free conditions. In a study of IL-10k k mice colonization with Lactobacillus plantarum 299v was performed 2 weeks before transferring from a germ-free environment to a specific pathogen-free environment (84). This treatment led to a reduction in disease activity and a significant decrease in mesenteric lymph node IL-12 and IFN-g production. A role for Lactobacillus reuteri in prevention of colitis in IL-10k k mice was also demonstrated (81). In this study, the oral administration of the prebiotic lactulose (shown to increase the levels of Lactobacillus species) and rectal swabbing with L. reuteri restored Lactobacillus levels to normal in neonatal mice, originally found to have low levels of lactobacilli species. This effect was associated with the attenuation of colitis. In a placebo controlled trial, orally administered Lactobacillus salivarius...

Range of biomarkers used to investigate health benefits

Key targets for intervention with functional dairy products include gut and oral microbiota, gastrointestinal functions, immunological and defense systems, mucosal systems and integrative functions (e.g., quality of life). Some promising or developing targets include bone and cardiovascular health and mental state performance. Thus, numerous biomarkers related mostly to disease have been exhaustively listed in previous publications (Crews et al., 2001 Saris et al., 2002). The reader is particularly referred to two recent supplements of the European Journal of Nutrition (Asp et al., 2003, 2004). In these supplements, biomarkers presently available for assessing the effects of food components on cardiovascular disease bone health and osteoporosis physical performance and fitness body weight regulation, insulin sensitivity and diabetes risk diet-related cancers mental state and performance gut health and immunity are thoroughly described and discussed.

Surrogate Markers For Dietrelated Colon Cancer Studies

As discussed above, the gut microbiota has been implicated in the etiology of CRC by a number of studies and these observations form the theoretical basis for the use of several gut microbiota biomarkers (fecal biomarkers) in studies on diet and colon cancer. They are composed of two main categories those examining the activity of bacterial enzymes or bacterial metabolites and those based on bioassays on fecal water. For a more thorough review of this subject, the reader is referred to Rafter and coworkers (67).

Prenatal Antecedents of Allergies and Asthma

At birth others emerged as the infant monkey developed across the first year of life. For example, the infants established atypical profiles of gut bacteria, with lower concentrations of beneficial Lactobacilli and Bifidobacteria, when generated from stressed pregnancies (Bailey et al, 2004). In turn, with reduced numbers of the protective microbiota, the infants were more vulnerable to enteric pathogens like Shigella and Campylobacter, two diarrhea-causing bacteria, especially during the subsequent stressful event of weaning (Bailey and Coe, 1999).

Environmental factors

Macrophage bactericidal properties, intestinal permeability to macromolecules, contractile activity and microcirculation. Finally, cigarette smoking may modulate the IBD phenotype, increasing the risk of CD in smokers and the risk of UC in non-smokers (Bridger etal., 2002). The resemblance between CD and infectious disorders such as intestinal tuberculosis or yersi-niosis suggested that CD may be an infectious condition. The effect of bacterial colonization on the digestive tract in genetically engineered animal models and the clinical effect of some antibiotics and intestinal flux manipulation in the human disease reinforced the idea that IBD may be related to certain bacterial species. However, the main argument in favour of infectious agents in CD came from genetic studies showing an association between CD and CARD15 NOD2 (see below). The gut flora as a whole is usually proposed to be an etiological factor for IBD and these diseases are considered to be an abnormal response to the...

Dehydroxylation of phenols

Many studies have detected the removal of the para hydroxyl group in catechols, usually by gut flora. Little information is available about the enzymes involved. Dehydroxylation of dihydrocaffeate occurs, for instance, in conventional rats, but not in germ-free animals A557 . Rats, fed with l-dopa and dopamine form small amounts of m- hydroxy analogues and metabolites A2961 the excretion of m -hydroxy metabolites formed from dietary plant catecholic compounds is dramatically reduced in germ-free rats compared with conventional rats, indicating that gut flora are involved H73 . However, studies with rat brain striatum have shown that trace amounts of dopamine are converted into m - and p-tyramine C465 .

Three ecological postulates that underlie conservation biology

Coevolution involves a series of reciprocal adaptive steps during which two or more interacting species respond to one another evolutionarily. A study of mammalian grazing ecology offers many classic examples of coevolution. Ruminant artiodactyls have evolved fermentation chambers that shelter legions of microscopic flora and fauna. These microbial sym-biants extract the energy and nutrients they need from the vegetation consumed by the host-ruminant. In return, the gut-flora ferment cellulose, providing energy and repackaging nitrogen for their hosts. Grazing mammals, in turn, structure the vegetative communities of their grassland habitats. Higher-order coevolution has been demonstrated among species of grazing ungulates, particularly in Africa. Thomson's gazelles, or tommies (Gazella thomsonii), for example, are so small that they cannot effectively exploit the tall grass that grows rapidly after the first rains of the wet season. So, just as other grazers depart the depleted...

Development of bifidobacteria in the intestine and beneficial effects

Bifidobacteria form part of the normal intestinal microbiota of human infants and adults and are believed to play a beneficial role in maintaining the health of the host. During birth and the first few days of life, bifidobacteria, amongst other intestinal microbes acquired from the mother and the surrounding environment, colonize the infant intestine (Favier et al., 2003). A succession of microbes occurs commencing with aerobes such as enterobacteriaceae, that create reducing conditions favourable to more strict anaerobic bacteria including the bifidobacteria (Franks et al., 1998 Mackie et al., 1999). The changing microbial ecology is coincident with a marked functional and morphological maturation of the infant gut barrier functions and immune system development (Cebra, 1999 Hooper, 2004). The microbiota in breastfed infants is usually dominated by bifidobacteria within a few days, but following a short delay they also reach high numbers in formula-fed infants (Harmsen et al., 2000a...

Summary of Research on Information Value

Table 22.1 summarizes the results of the above studies. The categories of OTC healthcare products that show the most promise for the early detection of disease outbreaks include pediatric electrolytes for large outbreaks of respiratory and gastrointestinal disease in children (including disease caused by influenza virus, rotavirus, and respiratory syncytial virus) flu remedies, chest rubs, and cold, cough, sinus, and allergy medications'' for large outbreaks of respiratory disease diarrhea remedies for waterborne outbreaks of cryptosporidiosis and other gastrointestinal pathogens and thermometers, pediatric cough syrups, and pediatric antifever medications for outbreaks of influenza.

Plant phenolics in human health and as antioxidants

It is evident that plant phenolic compounds constitute one of the most numerous and widely distributed groups of substances with more than 8000 phenolic structures currently known (28). In addition to stress linked phenolics coming only from the shikimate and phenylpropanoid pathways, a number of the phenolic compounds are found in plants, including the flavonoids that contribute to the characteristic flavor and fragrance of vegetables, fruits, tea, and wine. These compounds, which come from phenylpropanoid and polyketide (acetate-malonate) pathways, also have biological properties that are beneficial to human health. Flavonoids such as quercetin and catechin and isoflavonoids, genistein for example, are being investigated for properties which may reduce the incidence of cancer (22,23). Flavonoids and isoflavonoids are a class of phenolic compounds that have appeared sequentially during plant evolution and are simple aromatic compounds generated from both the phenypropanoid and...

Detection of Outbreaks

Yih et al. (2005) used the detection algorithm method to study retrospectively 110 gastrointestinal disease outbreaks in Minnesota. They studied daily counts of the CDC DoD Gastrointestinal, All code set. The detection algorithm they used was a space-time scan statistic algorithm

Biological Relevance of Gut IgA for Immune Homeostasis

Fig. 1a, b Regulation of gut bacterial communities by IgA. FACS profiles of lamina propria cells, and composition of small intestine microbiota from AID- - mice (a) without and (b) with B220-IgA+ plasma cells, reconstituted after parabiosis with normal mice. Intestinal flora in the biopsies from upper and lower segments of the small intestine of aged matched AID- - mice was analyzed based on culture-independent 16S rRNA sequence analyses Fig. 1a, b Regulation of gut bacterial communities by IgA. FACS profiles of lamina propria cells, and composition of small intestine microbiota from AID- - mice (a) without and (b) with B220-IgA+ plasma cells, reconstituted after parabiosis with normal mice. Intestinal flora in the biopsies from upper and lower segments of the small intestine of aged matched AID- - mice was analyzed based on culture-independent 16S rRNA sequence analyses Our own studies on mice deficient for AID, which have a complete block of CSR and SHM and thus are able to produce...

Conclusions and Perspectives

Intestinal IgA plasma cells are generated by multiple, intricate pathways in both organized (PP, ILF, MLN) as well as nonorganized (LP) gut structures. Fig. 4 Multiple pathways for generation of IgA in gut. Schematic representation of gut, with organized lymphoid structures, Peyer's patches (PP) and isolated lymphoid follicles (ILF), and diffuse tissues of lamina propria (LP). PP and ILF are composed of a subepithelial dome rich in dendritic cells (DCs), T cells, and B-cell follicle(s) that contain germinal centers (GCs). In these organized follicular structures B cells undergo efficient class switch recombination to IgA and somatic hypermutation and acquire gut-seeking properties through activation of integrin a4p7. Migration of both IgM+ and IgA+ B cells into the intestinal villi takes place through MadCAM-1+ postcapillary venules (PCV) and does not require NIK-dependent activation of NF-kB in LP stromal cells (LP-SC). In the absence of PP or ILF, IgA plasma cells are generated by...

Increasing Numbers of Beneficial Microbes

One of the properties thought to be important for the health benefits of consumed probiotic organisms is their ability to adhere to the intestinal mucosa. As such they can resist peristalsis and occupy a habitat at the expense of potentially harmful organisms. The probiotic applications to the human gut are already widespread, and evidence is mounting that these organisms have a beneficial effect on the host. It is now well established that the probiotic organisms can transiently establish themselves in the GIT and inhibit the adhesion and growth of enteropathogens. Table 5 delineates the effect of feeding selected probiotic preparations on the human gut microbiota.

Basic Formulation A Low Dose Linearity

The hypothesis driving risk predictions for genotoxic carcinogens since the mid-1970s is that at low doses, the dose-response relationship is linear. Crump et al (3) observed that, in environments containing significant amounts of carcinogenic processes, the carcinogenic effect will increase proportionately to the amounts of carcinogen added. They noted that, if individual cancers arise from a single transformed cell and the agent in question acts additively with any ongoing process, then under almost any model the response will be low-dose linear. Figure 1 illustrates this concept. It applies primarily to carcinogenic processes in which the agent acts at the cellular level to produce heritable genetic or epige-netic change, but may not apply to indirect influences (e.g., pH changes or dietary modifications that lead to modifications of gut flora) (3).

Principles of B Cell Selection in Galt Gc

This general scenario predicts that B cells leaving GCs in the GALT express a broad repertoire of somatically mutated BCRs, whose specificities would only partly be generated through classic affinity maturation, although it is still possible that antigen recognition through the BCR is required for the cells to transit into a post-GC compartment. A further step of selection of the cells on the basis of antigen recognition could be their trapping in the LP of the gut, where plasmablasts expressing somatically mutated IgA antibodies of a restricted repertoire are indeed found (Stoel et al. 2005). Thus the LP, in addition to the GC light zone, may serve as a site of B cell positive selection, where GALT GC emigrants which specifically migrate into this location (Craig and Cebra 1971) are selected by an ever-changing antigenic environment that originates from the gut flora, and where cells expressing useless BCRs are eliminated (Husband and Gowans 1978), like T cells lacking...

Solid organ transplant recipients

Clinical sequelae of HHV-6 may result from symptoms directly attributable to the virus or from its immunomodulatory effects. Table 1 shows a summary over the clinical syndromes that has been suggested being associated with HHV-6. Symptomatic infections seem to be more common in SCT than in SOT patients although published reports vary from very limited clinical effects of HHV-6 to a contributing effect on overall mortality. A fever of unknown origin with or without a skin rash bone marrow suppression, and encephalitis are the most frequently observed clinical features of HHV-6 (Carrigan et al., 1991 Drobyski et al., 1993 Carrigan and Knox, 1995 Wang et al., 1999 Ljungman et al., 2000 Zerr et al., 2001). Less commonly, interstitial pneumonitis, gastrointestinal disease, and hepatitis have been reported (Cone et al., 1993 Singh et al., 1997 Rossi et al., 2001 Hentrich et al., 2005).

Suppressing Numbers of Potentially Harmful Microbes

The artificial manipulation of the human intestinal microbiota by consumption of large numbers of probiotic microorganisms may lead to the presence of large numbers of lactic acid-producing microorganisms in the small intestine. Any available sugars will be quickly fermented to various organic acids and or ethanol. This leads to a change in the environment where the production of various low-molecular toxic metabolites and antigenic macromolecules by various intestinal, potentially pathogenic microbes and the effects of endotoxins may be strongly reduced (Table 5). The intestinal growth of all other types of nonintestinal pathogens is strongly inhibited by abundant probiotic fermentation in the small intestine. Reduction of viral infectivity was attributed to ethanol or acid-mediated denaturation of viral envelope proteins. In addition to organic acids, bacteriocins, such as e.g., Lactacin F (88), and some unidentified compounds synthesized by probiotic organisms Table 5 Effect of...

Dairy products and probiotics in childhood disease

3.2.1 Development of the intestinal microbiota in the first years of life - role of breast feeding, prebiotics and infant diet Current data suggest that the intestinal bacterial microbiota undergoes substantial changes in the first year(s) of life and remains relatively stable thereafter, although factors such as acute or chronic intestinal diseases, antibiotic treatment and the composition of the diet influence the composition of the microbiota (Barbut and Petit 2001 Hooper and Gordon, 2001 Nowrouzian et al., 2003 Tannock, 2001 (see Fig. 3.1). Endogenous mechanisms for control of bacterial growth in the intestine include gastric acid production, secretion of gastric, intestinal and pancreatic proteases such as pepsin, trypsin, chymotrypsin or lysozyme, bile-derived detergents, secretion of intestinal bactericidal peptides and IgA (Eckmann, 2005 Fahlgren et al., 2003 Mowat, 2003 Sarker and Gyr, 1992). While the intestine in utero is sterile under physiological conditions, a postnatal...

Enteral and parenteral nutrition

The metabolic role of the GI tract in both fasting and stressed states is increasingly recognized. The GI tract can act as a reservoir for bacteria that may cause systemic infections, by allowing bacterial translocation across the gut wall. Gut-derived endotoxin may therefore be the link between GI failure and multiple organ failure in patients without overt clinical evidence of infection. The relationship between GI bacteria, systemic host defences and injury in the development of bacterial translocation is complex. Enteral nutrition (EN) appears to modify antibacterial host defences, blunt the hypermetabolic response to trauma, maintain gut mucosal mass, maintain gut barrier function and prevent disruption of gut flora. This potential benefit acted as a driver for EN in preference to parenteral nutrition (PN). However a number of recent studies comparing (in large randomized controlled trials) EN versus PN have shown that the theoretical benefits do not necessarily translate into...

Reduction of nitro compounds to anilines

Formation of p -aminobenzoate from p -nitrobenzoate is observed in conventional rats, but is, relatively, very low in germ-free animals. Studies with microorganisms have found reduction by the gut flora Lactobacillus plantarum, Bacteroides fragilis, Peptostreptococcus productus, Clostridium, Proteus mirabilis, S. faecalis and E. coli A124 . The reduction rate in rat gut wall and contents is reduced by treatment with oral antibiotics, whereas liver activity is unaffected A3480 . p -Nitrobenzoate is reduced in the nematode Ascaris lumbricoides. Activity is found in the intestinal brush border but not in other tissues. The enzyme is cytosolic, it has a stability range of pH 4-7 (it rapidly loses activity at 0 outside this range), and has a sharp optimum at pH 6.5. It

That Regulates Microbial Communities in the

Abstract Our intestine is colonized by an impressive community of commensals that has profound effects on the immune functions. The relationship between gut mi-crobiota and the immune system is one of reciprocity Commensals have important contributions in nutrient processing and education of the immune system, and, conversely, the immune system, particularly gut-associated lymphoid tissues (GALT), plays a key role in shaping the repertoire of gut microbiota. In this chapter we attempt to discuss the mechanisms that underlie this reciprocity and emphasize the key role of mucosal IgA in maintenance of an appropriate segmental distribution of microbiota, which is necessary for immune homeostasis.


Ad infections occur worldwide as epidemic, endemic, and sporadic infections. Of the 51 human Ad serotypes currently known, the most common in clinical materials are the respiratory types of subgenus C (Ad1, Ad2, Ad5) and subgenus B (Ad3 and Ad7) (102,103). Along with being an important cause of respiratory tract infections, Ad can also cause conjunctivitis and gastrointestinal disease. Ads have been implicated in aseptic meningitis, encephalitis, hepatitis, and hemorrhagic cystitis and may cause severe disseminated infections in immunocompromised patients of all ages (104). In humans, the majority of Ad infections in immunocompetent hosts are subclinical, meaning that no apparent symptoms are present. This feature has made Ad an attractive platform for numerous gene therapy applications, including cancer. However, like most human virus pathogens, Ads possess a substantial genetic armamentarium to interfere with the immune system of the host to ensure their evolutionary survival...


The bettongs and potoroos are mainly fungivores, eating a large proportion of the fruiting bodies of underground (hy-pogeous) fungi. In order to accomplish this, it is necessary that they have a well-developed sense of olfaction a large proportion of their cortex is devoted to this. Animals dig with their forefeet to access their diet. The well-developed fore-stomach of potoroids allows them to have sufficient time to digest the fungi and the gut flora fauna assist in providing essential amino acids that may be absent from the diet. Animals can exist almost exclusively on fungi, which provide a nourishing diet high in both protein and lipid. The fungi grow on the roots of eucalyptus and other native trees and their spores are activated during passage through the bettong's gut, thereby allowing germination at the site of defecation.


The normal microbiota of the human GI tract is a complex microbial community whose composition is defined by a number of factors (including host genomics, diet, age, bacterial succession, immune function and health status). In general, the predominant bacterial groups are relatively stable in healthy human adults. However, inter-individual variations are evident, reflecting the unique equilibrium of each person's GI ecosystem. In addition, examination of the microbial populations in more detail (i.e., investigations at the subspecies level) further demonstrates the complexity and dynamics of this bacterial community, and most probably reflects its adaptive nature. Interactions between the host and the gut microbiota have led some researchers to acknowledge that the human intestine is, indeed, intelligent based on Alfred Binet's definition of intelligence intelligence is the range of processes involved in adapting to the environment (13).


4.5.1 The role of the intestinal microbiota in functional constipation Relatively few studies have investigated the role of the intestinal microbiota in constipation. Using culturing methods, Khalif and colleagues (2005) found that subjects with functional constipation have an aberrant microbiota that presents as a suppression of bifidobacteria and lactobacilli as well as an increased pool of potentially pathogenic micro organisms, such as E. coli and enterobacteria. Patients suffering from severe constipation demonstrated the most pronounced changes. Another study focusing on constipated children revealed increased numbers of bifidobacteria and clostridia in constipation (Zoppi et al., 1998). and Szajewska, 2005). Koebnick and colleagues (2003) investigated the effect of another strain of lactobacilli, L. casei Shirota, in 70 subjects diagnosed with chronic constipation. In comparison to placebo, L. casei Shirota supplementation resulted in improvement in the severity of constipation...

Future trends

Functional dairy products clearly possess potential to improve intestinal health. Milk as such is a healthy food. Certain lactobacilli strains already have established evidence for their shortening effect in the duration of acute diarrhoea, especially in rotavirus infections. However, vaccination against rotavirus is starting and the need for improved treatment may be reduced. There are still only a few studies on the successful treatment of invasive acute diarrhoea with native lactobacilli, but a promising experimental trial to bind cholera toxin with a genetically modified probiotic strain has recently been published (Focareta et al., 2006). Other intestinal disturbances, such as IBS, are also of interest to many dairy food producers, but this area still needs further studies to prove efficacy. Also a better understanding of the mechanisms and origin of the symptoms would certainly help in the development of effective preventive and treatment agents, including probiotics. In any...


Anthocyanidins and anthocyanins have been reported previously as having several positive effects on health (35,65-72). Much of this evidence has been derived in vitro and very little is known about their bioavailability in vivo. Previous human and rat studies have reported very low recoveries of intact anthocyanins in urine (73). Very little is known of the specific fate of the balance of these compounds. Given their structure, it is likely that they will undergo substantial metabolism by the human gut microbiota in much the same way as any other flavonoid structure. And yet, studies performed in the 1970s indicated that degradation of anthocyanins by the microbiota occurs to a much more limited extent than with other flavonoid structures (61). However recent studies investigated in vitro whether the anthocyanin glycosides, cyanidin-3-glucoside, and cyanidin-3-rutinoside were deglycosylated and whether the resulting aglycones were degraded further to smaller phenolic compounds by...


This review highlights the extent to which certain polyphenol classes undergo metabolism and structural alteration in the colon, and suggests that much of the prescribed in vivo health benefits of polyphenols may be due to secondary metabolites of polyphenols rather than the original compounds. Only a limited amount of research has been targeted at specifically trying to identify actual species of the human gut microbiota that are responsible or capable of metabolizing polyphenols. This is perhaps a reflection of the difficulties encountered in undertaking such an effort. Simply isolating single strains of bacteria anaerobically and carrying out suitable fermentation assays when presented with such a complex mixed culture of bacteria is an extreme challenge in terms of the laboratory time required. Furthermore much of the microbial mass in the colon remains to be described or cultured (85,86). In terms of the metabolic pathways that polyphenols follow during...

The Large Intestine

It is becoming increasingly evident that the large and complex bacterial population of the large intestine and their metabolism has an important role in toxicity of ingested chemicals and in cancer (28-31). A number of potential mechanisms have been proposed whereby gut bacteria may impact carcinogenesis. They may have a direct effect through the binding of potential mutagens and thus reduce exposure to the host (32). The normal microbiota present in the gut is known to produce and release toxins, which can bind specific cell surface receptors and affect intracellular signal transduction (33). Bacterial involvement in CRC has been widely studied with most information being derived from animal work and some human studies. Evidence from a wide range of sources supports the view that the colonic microbiota is involved in the etiology of cancer (Table 1).

Bacterial Enzymes

A wide range of enzyme activities capable of generating potentially carcinogenic metabolites in the colon are associated with the gut microbiota, including b-glucuronidase b-glucosidase, nitrate- and nitro-reductase. These are usually assayed in fecal suspensions and appear to be present in many bacterial types. Of these enzymes, b-glucuronidase has been the most extensively investigated as a biomarker of CRC risk. It should be noted that


Nitrate, ingested via diet and drinking water, is reduced by gut bacterial nitrate reductase to its more reactive and toxic reduction product, nitrite. Nitrite reacts with nitrogenous compounds in the body to produce NOC. The reaction can occur chemically in the acidic conditions prevalent in the human stomach and can also be catalyzed at neutral pH by gut bacteria in the colon. The primary bile acids, chenodeoxycholic acid and cholic acid, are subject to extensive metabolism, predominantly 7-a-dehydroxylation, by the intestinal microbiota, which converts cholic to DCA and chenodeoxycholic to LCA. These are termed secondary bile acids. Gut bacterial enzymes and fecal metabolites are relatively simple to measure routinely and in general may be of use in assessing effects of diet on modulating exposure of the colon to potential carcinogens, rather than reflecting cancer risk.

Germ Free Animals

Considerable achievements have been made since the 1970s in investigating the role of the gut microbiota using germ-free animals. Germ-free animals have enabled investigation of animal gut physiology in the absence of the gut microbiota. Studies using germfree animals have revealed that the gut microbiota is indeed of tremendous importance for the biochemical properties of the GIT, by metabolizing compounds in ingested feed and host factors of mucosal and pancreatic origin. Data from these studies revealed that many physiological and biochemical features of the GIT are indeed the result of microbial gut activity (79,80). The gut of germ-free animals have different physiological and biochemical properties to that of CV animals. The biochemical properties of germ-free and CV animals are often regarded as either germ-free associated characteristics (GAC) or microbiota associated characteristics (MAC). The characteristics of MAC and GAC are described in the chapter by Norin and Midtvedt.

Functional genomics

Upon arrival of the post-genomic era, the focus of studies on gut microbiota and its members has shifted from composition and activity to include the study of the functional products of gene expression. Using emerging techniques, such as transcriptomics and proteomics, the molecular activity of the microbiota can be studied in situ on different levels. As explained in the section 'Taxonomy and typing of bifidobacteria colonizing the human intestine', even microbes for which no genome sequence is yet available can be studied using so called smartman arrays, although a complete genome sequence of a related microorganisms will substantially facilitate interpretation of the data. Thus it is now feasible to study the transcriptome of the bifidobacterial community within the intestinal microbiota using bifidobacterial microarrays (Boesten et al., unpublished). Using well-established methods good quality total RNA can be isolated from faecal samples (Zoetendal et al., 2006c). Total RNA...

Patients with AIDS

Another feature of HCMV infections in AIDS patient was that high levels of viral replication as detected by the presence of viral DNA in peripheral blood could exist for a considerable period of time prior to the onset of disease (Bowen et al. 1995 Spector et al. 1998 Emery et al. 1999). Disease manifestations of HCMV infection unique to AIDS patients included end-organ disease in two organ systems, the gastrointestinal tract and the eye, both of which were uncommon sites of end-organ disease in even the most immunocompromised allograft recipient. The pathogenesis of disease in the gastrointestinal tract is still unclear but included the presence of focal areas of virus replication, focal colitis, and chronic dysfunction of the absorptive functions of the intestinal tract (Francis et al. 1989 Wu et al. 1989 Dieterich and Rahmin 1991 Wilcox et al. 1998). Gastrointestinal disease secondary to HCMV is infrequently seen in transplant patients and is not well described in infants with...

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