Bifidobacteria contributes to enhanced natural immunity, improves digestion and nutrient absorption, supplies B vitamins and normalises bacterial overgrowth. The metabolic properties of the gut flora may be readily changed by the regular consumption of dietary supplements of lactobacilli and bifidobacteria, as which they may mitigate certain undesirable effects of the gut flora.

Digestive disorders in the newborn and the elderly
Intestinal flora overgrowth
Pathogenic organisms (including Candida albicans)
Chronic skin conditions (including psoriasis)
Diarrhoea
Diverticulosis
Eczema
Constipation
Flatulence
Colitis
Irritable bowel syndrome
Post-antibiotic use
Post-gastrointesinal radiation exposure

Bifidobacteria have characteristic morphology, physiology, biochemical characteristics, cell wall constituents and DNA composition. They are found predominantly in the colon of human infants and adults. There are human and non-human species and biotypes.

Bifidobacteria constitute a major part of faecal flora of healthy humans. They are the predominant organism in the stools of breast-fed infants.

During prenatal life the foetus lives in a sterile environment, but the infant at birth is contaminated with the mother’s vaginal and faecal flora, and bacteria from the environment and food. This results in a rapid colonisation of the intestinal tract with a diverse microbial flora consisting principally of coliforms, Enterococci, Lactobacilli, and Clostridia. Bifidobacteria appear in the stools from 2 - 5 days after birth in breast-fed babies, with the establishment of a relatively stable microflora in the colon after several days.

By the end of the first week, Bifidobacteria become the predominant organisms in the faecal flora and rise to about 99% (range from 85% to more than 99%), while other bacteria decrease more or less rapidly. Coliforms, Lactobacilli and Enterococci comprise about one per cent of the faecal flora; and anaerobes, such as Bacteroids, Clostridia and other putrefactive organisms are drastically reduced and may disappear. The pH values of the stools range from 5.0 to 5.5 or slightly higher. In premature infants Bifidobacteria may proliferate more slowly than in full term infants, and only become predominant about 15 days after birth or even later.1–10 Infants born today do not demonstrate near the amount of bifidobacterium that was the case even 40 years ago.

Weaning of the infant causes a gradual change of ion

The microbial contamination of the infant begins at birth with colonisation of the gastrointestinal tract, and it persists throughout the adult life, during which new strains of microorganisms are contributed.

Petuely and Lindner (1957) found that the faeces of bottle-fed infants, occupying the same room as breast-fed infants contained 25% of the strains of Bifidobacteria typical of breast-fed infants.20 Likewise Mitsuoka and Kaneuchi observed variations in the incidence of species and types of Bifidobacteria in the faeces of infants at different hospitals, although infants at the same hospital had similar strains of Bifidobacteria in their faeces.21

Patients in hospitals may also acquire strains of microorganisms typical of the environment. It has been shown that oral tetracycline therapy frequently increases the incidence of facultative pathogens ( including Proteus spp., Klebsiella spp., S. aureus and C. albicans) in the stools of hospitalised patients but not in the case of non-hospitalised ones.22

Humans are usually exposed to a variety of microorganisms in their diet. Most of these ingested microorganisms are destroyed in the stomach, but some, such as acid-tolerant organisms and spore formers, may escape the acid barrier and enter the intestinal tract as transient strains. Kauffmann found, for example, the same E. coli serotypes in the stools of persons feeding in the same communal ,and other studies have reported frequent great contamination of food and eating utensils in canteens with E. coli.23,24,25

In gastric achlorhydria or hypochlorhydria the ingested microorganisms, including pathogenic bacteria, may represent a potential hazard to health.16,26

The malnutrition of tropical residents, together with a greater exposure to microorganisms, can result in increased bacterial population in the small intestine.19,27,28

Several antibiotics affect the facultatively-anaerobic flora of the intestine, and such antibiotics as clindamycin, and lincomycin have drastic effects on the indigenous gut bacteria, including Bacteroids, Bifidobacteria, anaerobic cocci and Lactobacilli.29,30

Treatment of mice and guinea pigs with antibiotics increases their sensitivity to infection by Shigella spp., and to Vibrio cholerae in the case of guinea pigs.82 Mice treated with streptomycin show increased sensitivity to Salmonellae.83

Irradiation of the abdomen with gamma or X-rays may also upset the normal microbial balance and give rise to abnormal gut flora.1,15

An abnormal distribution of the bacterial flora in the gastrointestinal tract leads to bacterial "overgrowth" of the stomach and small intestine. The balance of the faecal flora is also disturbed.

The abnormal gut flora is similar in infants and adults, but the causes may differ.

In infants, even small influences such as a sudden change in nutrition, common infections, vaccination, convalescence, sudden changes of the weather, and possibly other factors may upset the microbial balance in the gastrointestinal tract.

In adults, more drastic influences such as disturbances of gastric function, disorders n intestinal motility, and some diseases, cause changes in the gut flora.

Examples include

a) achlorhydria resulting from ageing, or associated with pernicious anaemia
b) stagnation of the intestinal contents due to blind loops
c) disorders and diseases impairing intestinal motility, e.g. diverticulitis of the small intestine, regional enteritis (Crohn’s disease) scleroderma, x-ray irradiation of the abdomen, intestinal strictures
d) gastrocolic and enterocolic fistulae
e) liver cirrhosis
f) disorders of immunological systems, e.g. hypogammaglobulinaemia
g) enteric viral infections
h) and consumption of certain antibiotics.1,15,19,31,32,33,34

Changes in the gut flora are non-specific, and the stomach and small intestine harbour large numbers of bacteria, particularly facultative anaerobes. The stomach of fasting individuals subject to achlorhydria or hypochlorhydria may contain many times the number of microorganisms than in the normal stomach.26,35

Achlorhydria also causes an increase in the number of bacteria entering the small intestine.19

In achlorhydria, Bifidobacteria may disappear or be considerably reduced in the faecal flora, but facultative anaerobes (mostly Enterobacteria and Enterococci) increase significantly. There are also Staphylococci, Proteus, Clostridia, the Klebsiella-Enterobacter group, and yeasts. Various other factors cause similar changes in the gut flora.

Bacterial "overgrowth" of the stomach and small intestine has harmful consequences. Organisms compete with the host for nutrients, and frequently degrade intestinal enzymes and other secretions (e.g. bile salts) In the blind loop syndrome, bacteria consume vitamin B12 (resulting in megaloblastic anaemia), and they deconjugate bile salts, leading to fat malabsorption and steatorrhea.19,31,32,36

The normal gastrointestinal flora may be re-established when influences causing abnormal distribution of intestinal microorganisms are eliminated, and re-establishment of normal flora may be accelerated by the dietary administration of lactobacilli (e.g. L. acidophilus) and Bifidobacteria.

With gastroenteritis, the appearance of the particular pathogen in large numbers is the major characteristic of these changes in the gut flora.

Intestinal pathogens associated with gastroenteritis cause acute diarrhoea, and their location is dependent of the species. Thus salmonellae grow in the small and large intestine, Shigellae in the large intestine, and enteropathogenic E. coli may be located in either the small or large intestine. In children the pathogenic strains of E. coli probably grow and produce enterotoxin in the small intestine. Vibrio cholerae and Clostridium perfringens also grow in the small intestine and thus, the microecology of the bowel is disturbed.19,36,37

The small intestine is found to contain an increased number of normal intestinal bacteria, while the faeces contain, in disorderition to large numbers of pathogens (10-100 per gram), an increased number of Enterobacteria and a reduced number of anaerobes including Bifidobacteria.

The protective mechanisms of the host include the gastric-acid, the motility of the small intestine, competition of the normal intestinal flora, and the immune systems.1,16,19,26,33,38,39

Tissier (1958) was the first to report an antagonistic effect of Bifidobacteria against B. coli, B. lactis aerogenes, R. ramosum and F. furcosa.40 This effect was also observed against Staphylococci and Proteus41, Salmonella typhi42,43 and Shigella dysentriae.44

Studies by Rose and Gyorgy (1955) showed that Bifidum var pennsylvanicus inhibits the growth of E. coli and even other strains of Bifidobacteria.45 Other workers have also reported an antagonistic effect of Bifidobacteria against enteropathogenic E. coli strains, Shigella dysentriae, Salmonella typhi, Staphylococcus aureus, Proteus and Candida albicans.46,47,48,49,50,51

A protective role of the gut microflora against enteric infections has been the subject of a few investigations. For instance, studies on breast-fed infants in Guatemala demonstrated that the gut microflora enhances resistance to the infection, or eliminates the invader.52 Other studies demonstrated that the low incidence of enteropathogenic E. coli infections in breast-fed infants was attributable to the presence of Bifidobacteria.10

A protective effect of Bifidobacteria against enteropathogenic E. coli strain 0111B4 was also observed in infants which were either nursed or given fresh, raw, bacteriologically safe human milk.53

The higher acidity of the lower intestinal contents may indirectly prevent the production of toxic amines from amino acids by the putrefactive bacteria (Clostridia, coliforms). The beneficial roles of Bifidobacteria and L. acidophilus in preventing the formation of amines have been reported.54,55

Bifidobacteria may not exert an inhibitory effect on enteric viruses, since in enteric virus infections most of the intestinal bacteria, including Bifidus organisms, quickly disappear from the faeces.56,57 However, upon elimination of the infection, the dietary administration of Bifidobacteria (preferably in conjunction with L. acidophilus) may be used to re-establish a normal gut flora.

Comparative feeding studies of two groups of infants, one receiving a modified cows milk-preparation containing Bifidobacteria and growth promoting substances, and the other receiving a buttermilk preparation, showed that enteric infections were 8 times more frequent in the buttermilk group than in the modified cows milk preparation group.58

Bifidobacteria, preferably in conjunction with L. acidophilus, may help prevent the overgrowth of harmful organisms in the intestine following antibiotic therapy. The growth of Bifidobacteria is inhibited and that of Candida albicans promoted during penicillin treatment.57 It has been shown that the oral administration of a Bifidus milk preparation to an infant following the discontinuation of penicillin treatment, increased the population of Bifidobacteria in the faeces and suppressed the growth of Candida albicans.57,59

Likewise, it has been shown that the oral administration of a freeze dried culture of Bifidobacteria to children with enteric infections, eradicated strains of enteropathogenic E. coli in about 60 % of cases, and in more than 80 % of cases when supplemented with lactulose.60

Bifidobacteria, when administered in conjunction with lactulose, have a relatively strong antagonistic effect against enteropathogenic E. coli. strains and this may be attributable to the lower pH in the large intestine. It has been suggested that the preponderance of Bifidobacteria in the large intestine of breast-fed infants and the low pH of the contents of the large intestine are the main factors responsible for natural resistance to gastroenteritis.62,63

Bifidobacteria have not been shown to produce antibiotic substances, but this area requires further study. In contrast, lactic acid bacteria have been shown to produce various types of inhibitory substances. L. acidophilus produces lactocidin, acidophilin, and acidolin.64,65,66 The possibility of lysozyme production by Bifidobacteria has been suggested on the grounds that egg white lysozyme and a metabolite of Bifidobacteria may have common antigenic determinants, but more evidence is needed to confirm this theory.67

Organic acids play a major role in the antagonistic effect of Bifidobacteria against many organisms both in vitro and in vivo. The increasing hydrogen ion concentration of the growth medium, due to the production of acids, inhibits acid sensitive bacteria. These acids differ in their antimicrobial effects and acetic acid has a stronger ability to inhibit microbial growth than lactic acid. It has been shown that the minimum pH values at which Salmonellae commence growth (under laboratory conditions) are 5.4 for acetic acid, 4.4 for lactic acid and 4.05 for citric and hydrochloric acids.68

Unlike the homofermentive lactic acid bacteria, Bifidobacteria produce more acetic than lactic acid from fermentable carbohydrate, and thus also produce small amounts of formic acid. The acid producing ability and the proportions of the fermentation products vary among different strains, even within the same species.

Organic acids present in their free (undissociated) forms may also have a direct toxic effect on other organisms.69,70 Acetic acid is present in both free and combined forms in the large intestine content and it may exert a decisive inhibitory effect on undesirable bacteria.

The presence of a buffer consisting of both acetic acid and acetate was demonstrated in the faeces of newborn infants, but not in those from bottle-fed infants. In vitro, an acetate-buffered medium was strongly bacteriostatic between pH 5.0 and 5.8 against gram-negative organisms, and at pH 5.4 and below against Clostridia. An unbuffered medium had no bacteriostatic effect on the growth of E. coli above pH 4.6, Salmonellae typhimurium above pH 5.0, Bacteroids above pH 5.6, Clostridium paraputrificum and C. perfringens respectively above pH 4.8 and 5.6.71,72

The gut microorganisms contribute to production of resistance factors including the humoral and cellular defence systems of the host, and the indigenous flora has its own protective function.

The lymph nodes (masses of lymphoid tissue) are larger and more numerous and the number of lymphocytes within the nodes is greater in infected than in germ free animals. Lymphocytes are major constituents of the lymphoid tissues, and are associated with specific immunity. B lymphocytes (made in the bone marrow) are associated with humoral immunity, and T lymphocytes (derived from the thymus gland) with cell-mediated immunity. Both types of lymphocytes, however, participate in the production of antibodies.

T lymphocytes and B lymphocytes attach simultaneously to different determinants on the antigen, which is previously fixed on the surface of the macrophage. The antigen interacts with a specific receptor on the T cell and induces this cell to release a signal to the B cell. In response to this signal , the B cell differentiates and proliferates into plasma cells that actually produce the specific antibodies. They include Gamma-A globulin (IgA), Gamma-D globulin (IgD), Gamma E globulin (IgE) gamma-G globulin (IgG) and Gamma-M globulin (IgM).

IgA comprises 13% of serum immunoglobulins. It constitutes the major immunoglobulin in mucosal secretions, especially from the gut and as well as in colostrum, milk and saliva (where it occurs as a dimer linked to epithelial cell surface receptors, the secretory piece that gives IgA resistance to proteolytic enzymes).73

IgA is the major immunoglobulin in the human serum (comprising about 80% of the serum immunoglobulins of the adult), crosses human placenta and fixes complement, while IgM comprises 5 - 10% of the serum immunoglobulins and fixes complement. IgD occurs in small amounts, and IgE is associated with reaginic antibodies.

The formation of each type of immunoglobulin in dependant on clones. Genes occurring in different cell lines are called clones and each clone makes a single type of antibody. A specific antigen, introduced into a single vertebrate, simulates one specific clone of lymphocytes to proliferate, while the other clones are repressed.74

Recent evidence suggests that indigenous (autochthonous) microorganisms are less immunogenic in their host than allochthonous microorganisms of similar types.75,76 Some indigenous microorganisms have antigens that are chemically similar to antigens of their host’s tissues or even seem to have antigens in common with their host. Some strains of E. coli have antigens in their cell-envelopes which are chemically related to antigens of the colonic tissue of humans.77 Likewise Bacteroids spp. fail to induce antibodies on parenteral injection into its native host, the mouse.76,78

Other indigenous microorganisms have antigens chemically different from the antigens of their host’s tissues, but they fail to induce antibodies if they reach high population levels early in the animal’s life.33 A strain of Lactobacillus, isolated from rats, did not induce antibodies in baby rats which were colonised immediately after birth by large numbers of Lactobacilli, but they induced antibodies when monoassociated with adult gnotobiotic rats.79 The explanation of this phenomenon may be that the bacterial antigens entered the animals early in life and in a sufficient amount to inactivate their immunological mechanisms.80 Alternatively, this process may be due to a link with the animal’s own acquired immunological tolerance, which prevents autoimmune response.

The relatively stronger immunogenic activity of allochthonous microorganisms compared with indigenous ones may be important when extrapolated to humans.

The gut microorganisms increase an animal’s resistance to intestinal infectious disease. They may prevent colonisation of an area in the intestinal tract by invading pathogens by competition for essential nutrients or for attachment sites on the epithelium.33,81

The gut microorganisms may inhibit the growth of invading pathogens by the production of organic acids, particularly volatile fatty acids, by the deconjugation of bile salts and by the production of bacteriocins. Bifidobacteria, Bacteroids, Eubacteria, Peptostreptococci and Ruminococci produce volatile fatty acids from carbohydrates and many of them deconjugate bile salts releasing free bile acids. Free bile acids are more inhibitory to susceptible bacteria than their conjugated forms.

Organic acids produced during the growth of some microorganisms (Bifidobacteria, Lactobacilli, Peptostreptcocci, Ruminococci, Bacteroids) stimulate intestinal peristalsis and indirectly the removal of invading pathogens from the intestinal tract.

An abnormal distribution of the microbial flora in the human gastrointestinal tract can have harmful consequences. Large microbial populations in the stomach and small intestine compete with the host for nutrients and they may degrade the digestive enzymes and bile salts. Moreover, a disturbed microbial balance in the large intestine (a reduction of Bifidobacteria and an increase in facultative anaerobes and potentially pathogenic organisms) affects the normal microbial metabolism.

The microbial balance in the intestines may be disturbed by antibiotic therapy and cause overgrowth of potentially harmful micro-organisms with pathological consequences.

Abnormal gut bacteria populations produce potentially toxic products, such as ammonia, phenols, pharmacologically active amines, and indole. If the detoxification function of the liver is impaired, then the metabolic activities of some gut micro-organisms may prevent a serious hazard. In cirrhosis or portal systemic encephalopathy, the liver is unable to detoxify ammonia, amines and phenols which re-enter the general circulation and cause intoxication. Many reports have indicated the role of Bifidobacteria in the compensational detoxification of subjects with chronic liver disorders.84,85

Gut bacteria such as Enterobacteria, Peptostreptococci, Clostridia and Eubacteria produce urease, which hydrolyses urea to ammonia and carbon dioxide. About 20 - 25% of the total urea production each day is hydrolysed.86 The ammonia formed in the gut thus passes via the portal blood system to the liver, where it is either converted into nonessential amino acids, or detoxified by the resynthesis of urea. The diseased liver, especially in cirrhosis, is unable to do this and ammonia enters the systemic venous system resulting in hyperammonaemia and intoxication.

The production of ammonia by the deamination of amino acids derived from milk proteins is small compared to those produced from the blood proteins contained in meat, and also meat proteins. Bifidus milk may prove beneficial for protein metabolism in cirrhosis.87,88 Thirty-three patients (3 older children and 30 adults) with various degrees of liver cirrhosis were given a reconstituted Bifidus milk preparation during an average period of a hundred days, but some received the preparation for up to two years. The dehydrated preparation contained 10 % protein, 84% carbohydrate including lactulose, and three percent minerals; also viable Bifidobacteria. Treatment began with an initial dose of 10 g three times per day, which was subsequently increased to 100 g three times daily. The authors observed that this Bifidus milk preparation produced an improvement in the patients, and decreased the ammonia, free phenols and indican in the blood. It also reduced faecal pH and increased the Bifidus content.

B. adolescentis may be used to correct a disturbed microbial balance in the large intestine after antibiotic therapy. Feeding an infant with a milk formula which contains viable Bifidus, with its growth factors, prevents the overgrowth of Candida albicans in the intestine following penicillin therapy.57,59

A recent report indicates the protective roles of B. adolescentis and L. acidophilus bacteria in dyspeptic conditions attributable to antibiotic therapy. The administration of a preparation containing antibiotic resistant B. adolescentis and L. acidophilus to children between 13 days and 8 years of age, during long-term, broad-spectrum antibiotic therapy for a variety of conditions, prevented the occurrence of dyspeptic disturbances, and these organisms were detected in the faeces of 50% of these patients even several days after termination of their administration.89 A disturbed intestinal flora in premature infants with septicaemia has been corrected by administering cultures of Bifidobacteria.90

Acute diarrhoea caused by enteropathogenic bacteria requires appropriate treatment with antibiotics, and the temporary reduction or withholding of food, while mild diarrhoea of short duration may be treated with special preparations made from strained carrots. However, B. adolescentis may be used as a supplementary treatment in enteric infections.90

The oral administration of a culture of B. adolescentis, in conjunction with a dietetic regimen, has been reported to produce beneficial effects in infants with bacterial enterocolitis. The food had a high fluid content, followed by cream rice and human milk.92 The oral administration of a freeze dried culture of B. adolescentis to children with enteric infections could eradicate enteropathogenic E. coli strains in about 60% of cases, and in more than 80% of cases when lactulose is included.60 The researchers did not, however, observe a parallel with the implantation of B. adolescentis and disappearance of enteropathogenic E. coli, but the rather strong antagonistic effect of Bifido bacteria when used in conjunction with lactulose (or comparable feeding), against enteric infections.

Many enteric infections and dyspeptic phenomena are located in the small intestine, where Lactobacilli occur in large numbers, along with Bifidobacteria. Consequently, the use of B. adolescentis with L. acidophilus may be justified.93,94

The oral use of L. acidophilus cultures in the treatment of the side effects of oral antibiotic therapy and therapeutic irradiation has been well documented.95,96,97,98

Subsequently, B. adolescentis has been used for the same purposes, but use of this organism together with L. acidophilus seems preferable. Many intestinal disturbances occur in the small intestine where Lactobacilli are more numerous than Bifido bacteria.

Bacterial preparations for therapeutic use should be administered in appropriate concentrations. For instance, the common dose of L. acidophilus is in the billions of viable cells per day.93,95,99

The use of an appropriate dietetic regimen during the period of administration of bacterial cultures is highly significant.100,101,102 The consumption of fermented milks containing acidophilus and Bifidus bacteria may assist in re-establishing the normal microbial balance, provided that the diet is not too rich in meat proteins.16

In general, digestion and the nature of the diet influences intestinal health.104,105 Digestive troubles are more likely to occur in elderly people. These are accompanied by alterations in the gastrointestinal flora, resulting in diminution or disappearance of Bifido bacteria from the faecal flora and an increase of Enterobacteria, Clostridia and Enterococci.

The administration of Bifidus milk to 12 patients (aged 67 - 92) with dyspepsia has been reported to give good results. They were treated for three weeks (3 times daily for 10 days and thereafter once daily) with 150 ml portions of a reconstituted viable B. adolescentis bacteria. Although no Bifido bacteria were detected in the faeces before treatment, they were detected thereafter.103

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