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In the study at King’s College London, 186 patients with IBS whose symptoms had not responded to conventional treatments were given the new probiotic in the form of a drink, at a dose of 1ml of drink per kilo of bodyweight. The number of published studies investigating probiotics has increased 15 fold in as many years, and 2011 looks set to be a record year with more than 1300 publications anticipated. This amount of research points to probiotics being more than a fad, it reveals a sustained significant commitment of resource to the therapy area.
For the consumer, this move towards rigorous scientific appraisal of probiotics means that there will be more and better information available about probiotics and their potential to support heath.
All the data used for this article came from the NIH PubMed database which is a publicly available service provided by the US National Library of Medicine.
It has long been know that there is a close interaction between the gut and brain in humans, consider the effect that nerves or anxiety can have on your digestion. A quick look at the range of probiotic products available on the chemist or supermarket shelf immediately reveals two segments; liquid products such as yoghurts or drinks, and dry products such as capsules, tablets and sachets.
Dry products come in many shapes and sizes, however the technology behind them is broadly similar and generally involves freeze-drying. With a few exceptions, live probiotic products, particularly the diary based products containing yoghurt or milk are single strain probiotics containing bacteria which thrive on the sugar found in milk; lactose (hence Lactobacillus).
There are those who believe that a single strain of bacteria may be all that is needed to confer benefit; Acidophilus species are a good example, and so there are plenty of producers of single strain freeze dried probiotic tablets, capsules and powders. As above, freeze drying allows for multiple species and strains to be combined in a single product without fear of competition, however other problems can arise as a result, chief amongst these being time to re-hydration and recover of function for the bacteria.
On paper, these products deliver the best of both worlds; providing several bites at the cherry in one go, and overcoming the problems with dry products. So, when we talk about probiotics, perhaps it’s important to specify what kind of probiotic we are referring to, at least to make the distinction between live and freeze-dried, but better still to start talking about which strain(s) are in the product. Manufacturers now have to submit supporting data to the regulatory authorities (EFSA) if they want to make health claims, and this data must be directly linked to the strain in the product. Science, Technology and Medicine open access publisher.Publish, read and share novel research. Figure 1 depicts yearly changes up to 2014 in the number of publications related to “probiotics OR prebiotics OR biogenics” as a whole (A) and those related to the stomach (B), based on a PubMed search. Sgouras D, Maragkoudakis P, Petraki K, Martinez-Gonzalez B, Eriotou E, Michopoulos S, et al.
Two-thirds were given the drink every morning before breakfast for three months, while the remainder were given a placebo. In 1997 there were roughly 80 publications globally per year referencing probiotics, today that figure is over 1200 per year or 100 publications per month.
Any form of research has a cost associated with it, if we were to conservatively estimate the average cost of these studies at $50,000 a piece then the investment over the last decade is close to half a billion US dollars.
The scientific and medical community take probiotics seriously; they would not commit more resource year on year to an area of research which they do not believe to be scientifically valid, and since the majority of these studies are investigator-initiated it is not simply that industry funding is driving the upward trend. There is a hunger for data; consumers and regulators alike are demanding scientific rigor and proof of effect before they part with their cash or accept the health claims of probiotic manufacturers. Probiotics are here to stay; not only are the number of published studies increasing year on year, but the scale of future studies is becoming more and more ambitious with academic institutes and manufacturers both announcing large, well designed studies which on paper look more like drug trials then investigations into a food supplement. With time we should find that decisions about which probiotic supplement we use can be based more on fact than on marketing. Today, Probiotic means product, in fact it means thousands upon thousands of products globally which have adopted the term. Certainly the different approaches and properties of the various products available today scream out for some sort of segmentation. Live products must also contain a source of nutrition for the bacteria; this raises several new issues, firstly storage and shelf-life which can be short for some live products (check the labels) secondly palatability since probiotic bacteria are not always tasty creatures in their own right.
It is possible to freeze simple organisms and cells under low temperature and pressure in such a way that all the water is removed without damaging the delicate structure of the cell or organism itself. These bacteria tend to be strains from the Bifidobacteria or Lactobacilli genera which are very common in the environment; leave a cup of milk out for a few days and you will gather hundreds of strains just from the air which will also do a nice job of turning your milk sour, or if you are lucky turn it into yoghurt. The human gut contains more than 500 different species of bacteria, so to take a single strain in an attempt to hit the bullseye may not always deliver success.
However the devil is in the detail and it is very difficult to deliver a multiple strain live product, which is why they are few and far between. This means that consumers will now face a further need to educate themselves about probiotics if they are to be equipped to make an informed choice. Effect of live Lactocacillus johnsonii No.1088 (LJ88) on the number of lactobacilli (A), bifidobacteria (B), and chlostoridia (C) in feces of human intestinal microbiota-bearing mice. IntroductionHistorically, probiotics have been thought as agents beneficial to improve the microbial environment in the intestines, but some strains of lactic acid bacteria have been used as probiotics, with the claim of providing health benefits to the stomach.Nestle’s Lactobacillus L.
The total number of publications shown in Figure 1A was 14,417, of which those including the word “stomach” (Figure 1B) were only 290 (about 2% of the total publications). Effect of fermented milk containing Lactobacillus johnsonii La1 (LC1) on defecation in healthy Japanese adults—A double blind placebo controlled study—.
Effect of whey-based culture supernatant of Lactobacillus acidophilus (johnsonii) La1 on Helicobacter pylori infection in humans. Detection of Lactobacillus gasseri OLL2716 strain administered with yogurt drink in gastric mucus layer in humans. Fermentation metabolites from Lactobacillus gasseri and Propionibacterium freudenreichii exert bacteriocidal effects in mice.
Influence of proton-pump inhibitors on the luminal microbiota in the gastrointestinal tract. Antagonistic activity against Helicobacter infection in vitro and in vivo by the human Lactobacillus acidophilus strain LB.
In vitro anti-Helicobacter pylori activity of the probiotic strain Bacillus subtilis 3 is due to secretion of antibiotics. Effect of Weissella confusa strain PL9001 on the adherence and growth of Helicobacter pylori. Inhibition of Helicobacter pylori infection in humans by Lactobacillus reuteri ATCC 55730 and effect on eradication therapy: a pilot study. Epidemiological and pathobiological profiles of Clostridium perfringens infections: review of consecutive series of 33 cases over a 13-year period. Current concepts in the management of Helicobacter pylori infection: the Maastricht III Consensus Report. Lactic acid-mediated suppression of Helicobacter pylori by the oral administration of Lactobacillus salivarius as a probiotic in a gnotobiotic murine model. In vitro inhibition of Helicobacter pylori NCTC 11637 by organic acids and lactic acid bacteria. In vitro and in vivo inhibition of Helicobacter pylori by Lactobacillus casei strain Shirota. Some of the studies, with large numbers of patients recruited will cost much more than this, some may run into millions of dollars for a single study. Also an important consideration is competition between bacterial strains within the same live product; they can compete with one another for resources in the bottle. In the case of probiotics this places the bacteria in a state of suspended animation which is well suited to long term storage (and convenient for supply chain management).
LJ88 in the measure of 109 cfu was orally administered once a day for two weeks, and the number of bacteria in feces was determined. Lactic acid produced by probiotic bacteria competes with the pH elevation by urease mentioned above, which makes the environment unsuitable for H. 1088 has antibacterial activity, including that against Helicobacter pylori, and inhibits gastrin-mediated acid production in mice.
This problem is one reason why it is very difficult to develop a multi-strain live product, although they are now becoming available. Once moisture becomes available to the bacteria they re-hydrate and a proportion of the bacteria will go on to function and divide again as they did before freezing. 1088 (LJ88) on the number of bifidobacteria in feces of human intestinal microbiota-bearing mice. This means that many strains can be combined into a single product, however there are downsides to freeze-drying, not least the high expectations placed upon bacteria to re-hydrate and regain function quickly after swallowing into the acidic environment of the stomach.
Mice with human intestinal microbiota were prepared by using germ-free mice and were then infected with H. Heat-killed LJ88 (109 and 1010 cells) were orally administered once a day for two weeks, and the number of bifidobacteria in the feces was determined.
In addition to acidification, lactic acid inhibits urease activity itself [22], which might be another molecular mechanism for lactic acid to inhibit survival of H. However, some probiotic strains have reported to reduce the extent of inflammation and to decrease the level of specific Immunoglobulin (IgG) against H. Furthermore, LJ88 not only has anti-pylori activity but also reduces excessive gastric acid production [7].

Ingestion of Lactobacillus strain regulates emotional behavior and central GABA receptor expression in a mouse via the vagus nerve. Probiotics and virulent bacteriaAlthough a very recent definition of probiotics is “live microorganisms, which when consumed in adequate amounts, confer a health effect on the host” [10], probiotics have been thought as agents that improve the balance of microbiota mainly in the intestines. But since not all lactic acid bacteria producing the same level of lactic acid can inhibit H. CoaggregationCoaggregation with pathogenic bacteria has been proposed as a mechanism by which probiotic bacteria can inhibit the growth of pathogenic bacterial. For example, the ability of heat-killed LJ88 to reduce excessive gastric acid production can be thought as having this property [7]. Moreover, some probiotic strains have been reported to inhibit the growth of some virulent bacteria, resulting in prevention of and recovery from diarrhea.As regards the stomach, H. In mice treated with either live or the lyophilized (freeze-dried) form of LJ88, the number of H. However, treatment with heat-killed LJ88 significantly decreased the number of gastrin-positive cells (right-side bar graph). Such food ingredients that beneficially affect the host by “direct” stimulation, suppression, etc., were defined by Mitsuoka as “Biogenics” [8].
Antimicrobial productsSome probiotic strains have reported to secrete antimicrobial substances other than lactic acid. Some strains of probiotic bacteria have been reported to be effective in reducing the number of H. So this mechanism can also be thought as one of the possible mechanisms for probiotic bacteria to inhibit H. The minimum inhibitory concentrations (MICs) were determined after cultivation for 48 h at 37°C.
Gastroesophageal reflux disease (GERD)Gastroesophageal reflux disease (GERD) is a chronic disease caused by backflow of gastric acid to the esophagus and is subjectively recognized mainly as heartburn. Although proton pump inhibitors (PPIs) have been strongly recommended, and their effectiveness against GERD is widely recognized, hypergastrinemia is a concern as a side-effect of long-term usage of PPIs [31].
Bacteriocins are being widely investigated as proteinaceous antimicrobial substances produced by bacteria [25]. The amount of lactobacilli, bifidobacteria, and clostridia in the feces of mice were determined before and after LJ88 administration.
This strain is now used mainly in fermented milk in Japan as LG21 and promoted as “lactic acid bacteria combating risk” (a catchy tag from Meiji).
In addition to these two strains of probiotic bacteria, some other strains have been reported to be effective in ameliorating symptoms derived from H.
In association with the administration of LJ88, the number of bifidobacteria and clostridia increased and decreased, respectively (Figure 3B and C). Since bifidobacteria are reportedly beneficial to human health due to their ability to regulate intestinal microbial homeostasis [17], the bifidobacteria-increasing effect of LJ88 is thought to be one of its beneficial effects on the intestines.
Although not all of the species belonging to clostridia are virulent, some of them are known to be harmful to human health, e.g. 1088 (LJ88) as a probioticRecently, we found a novel strain of lactobacillus, LJ88, in the gastric juice of a healthy human volunteer. So the effect LJ88 of reducing the number of clostridia in the intestines is another beneficial property of LJ88. So it would be beneficial to have the way to suppress hypergastrinemia possibly caused by PPI administration. Probiotics effective in reducing the production of gastric acidLJ88, as mentioned above, can reduce the number of H. The mechanism underlying this effect has been investigated, and it was found that LJ88 reduces the number of G-cells.
But the cost for such a therapy is expensive, and so a lower cost way to control the extent of H. Moreover, since the eradication rate of this triple therapy is not 100%, probiotics effective in increasing the eradication rate of triple therapy might be meaningful. Implications of proton-pump inhibitors for viability of gastric microbiotaThe stomach is considered to be a barrier to prevent virulent bacteria from entering the gastrointestinal tract due to its high acidity. However, irrespective of such a harmful condition for bacteria, a significant number of live bacteria exist in the stomach environment.
Such competition which is either specific or nonspecific, might be one of the potential mechanisms underlying the anti-H. However, since we do not have any evidence showing the existence of such resident bacteria in the stomach, “prebiotics for stomach” remains as a mere hypothesis for now. Of course, some beneficial indigenous bacteria may possibly be found in the stomach in the future. In such a case, “prebiotics for the stomach” will come to have a factual basis for further research and development.4.
Biogenics for the stomachBiogenics were originally defined by Mitsuoka as “food ingredients that beneficially affect the host by direct immunostimulation, suppression of mutagenesis, tumorigenesis, peroxidation, hyper-cholesterolemia or intestinal putrefaction” [8]. Gastric acid-reducing activity of heat-killed bacteriaOne of the characteristic effects of our LJ88 is the reduced production of gastrin, as mentioned above. We found that such an effect is the property of not only living bacteria but also heat-killed ones [7, 36], allowing LJ88 to be thought as a kind of biogenics for the stomach. The different treatments of these six experimental groups (Groups-1 to -6) are summarized in (Figure 4A). After the triple therapy, two groups (with and without triple therapy; Groups-3 and -4) were sacrificed and analyzed for the number of gastrin-positive cells as above.
These results suggest that LJ88, even in its heat-killed form, can prevent the increase in gastric acid after triple therapy by decreasing the number of gastrin-positive cells, the effect of which might be beneficial for prophylaxis of GERD. Since this result was obtained by using a mouse model, it should be examined whether or not the same mechanism works also in humans.Since live LJ88 were beneficial not only to the stomach but also to intestinal microbiota, as shown in Figure 3, we examined the effect of heat-killed LJ88 on intestinal bacteria by determining the number of bifidobacteria in the feces of human intestinal microbiota-bearing mice. Among them, some mechanisms can be expected to belong not only to live bacteria (probiotics) but also to heat-killed ones (biogenics).One possible mechanism might be competition between H. So some probiotic strains proposed to compete for adherence sites on gastric surface might have anti-H. However, no such examples have been reported to date.Another potential mechanism might be coaggregation with H.
So preventive and stimulatory effects of nonfermented and fermented soy foods should be considered taking these factors in mind. Since isoflavones are one of the proposed molecular candidates for preventing gastric cancer, a large-scale, population-based, prospective, cohort study was conducted to investigate the relationship between isoflavone-intake and risk of gastric cancer in Japan [42]. The results suggested that higher intake of isoflavones does not prevent gastric cancer [42].
So even if nonfermented soy foods can reduce the risk of gastric cancer, the responsible molecules might not be isoflavones in soy foods. Brassicaceae vegetable-related products as biogenics for the stomachVegetables of Brassicaceae classification, including cabbage and broccoli, reportedly contain S-methylmethionine, also known as vitamin U. Sulforaphone also has been reported to have protective and reparative effects against oxidative stress in gastric mucosa by stimulating nrf2 gene-dependent antioxidant enzyme activities, and also to have anti-inflammatory effects on gastric mucosa during H.
Bonifacio extensively reviewed such products, including 21 different plant extracts and 18 different essential oils [50]. Most of the extracts and essential oils, described in the review mentioned above, were examined only in vitro, although some of them have been evaluated in vivo as well. Among them, essential oils from Cymbopogon citratus (lemongrass) and Lippia citriodora (lemon verbena) were found to be bactericidal [55]. Thus, natural sources including herbal and medicinal plants can be thought of as future promising sources of new biogenics for the stomach.5.
Future directionsIn this report, we discussed probiotics, prebiotics, and biogenics for the stomach. As shown in Figure 1, this research area remains small to date, as only 2% of the total volume of publications concerning “probiotics, prebiotics, or biogenics” as a whole has focused on the stomach. However, the research efforts made related to this interesting research field, as mentioned in this review, are none the less very significant.
We think future research in this field will go in the following directions:Concerning probiotics for the stomach, a search for new probiotic strains beneficial to the stomach is warranted. Although no probiotic bacteria able to reside and grow in the stomach have yet been found, the possible existence of such a kind of so-called “extremophile” [56] type of probiotic bacteria cannot be denied in principle. Indeed, most researchers did not believe in the existence of indigenous bacteria in the stomach until 1984, when H. Other extremely acid-resistant probiotic strains that can survive in the stomach for a significant time period even if not able to grow there, such as our LJ88, will be a more promising type of bacteria as probiotics for the stomach.However, since “extremophile” probiotics or indigenous bacteria beneficial to the stomach have not been found to date, prebiotics for such bacteria are also unknown as well.

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