MODERN PROBIOTICS. ADVANTAGES AND DISADVANTAGES

How to tell if your baby is constipated

Constipation, or constipation, is commonly understood as a dysfunction of the gastrointestinal tract, manifested by rare stools, hardening and fragmentation of stool, and difficulty defecating 1.2. However, for young children there are no strict criteria for normal bowel movement frequency1. It depends not only on age, but also on the type of feeding of the baby. The consistency of stool is also assessed depending on the nature of the diet.

According to accepted standards, in children of the first four months of life (before the introduction of complementary foods) who are breastfed , the rectum should be emptied after each feeding, and the feces should have a uniform, mushy consistency. If stool occurs less than 4 times a day, and the stool becomes compacted, this is a reason to talk about constipation in a newborn or infant1,2.

At about 4-6 months, with the expansion of the child’s diet, stools become less frequent - 2 times a day. The feces are compacted and shaped into a cylinder1.

Formula-fed babies normally have bowel movements at least once a day at a certain time1,2. Feces are soft and cylindrical in shape1,2. In this case, there should not be any difficulties during bowel movements.

It should be kept in mind that stool frequency is not the only guide to diagnosing constipation in infants. Even if the frequency of bowel movements is within the age norms, but the baby’s stool is dense, fragmented and scanty, and the emptying of the rectum itself causes him suffering, this is a reason to talk about constipation in an infant or “artificial”1,2.

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Acipol

* For dysbacteriosis

1. According to IQUIA Solutions LLC data for January – December 2022. The average retail price for the drug Atsipol is 352 rubles 84 kopecks

2. O. V. Molochkova, O. V. Kladova, A. A. Novokshonov, N. L. Valts, Yu. V. Kompaniets, N. L. Grishkevich. Prevention of antibiotic-associated diarrhea in children with a lactose-containing probiotic. Children's infections 2016, No. 4, S 37-411

3. List of studies conducted:

Novokshenov A. A., Molochkova O. V. et al. The use of a domestic probiotic containing Lactobacillus acidophilus for the treatment of acute intestinal infections and other pathologies in children. Therapy issues. Children's infections 2022, No. 1. Kladova O. V. et al. Preventive and therapeutic effectiveness of Acipol for antibiotic-associated diarrhea in children // Children's infections. – 2009. – No. 2. – P.44-47. Maev I.V. et al. Possibilities for the prevention of idiopathic antibiotic-associated diarrhea in adults. //Russian Journal of Gastroenterology, Hepatology, Coloproctology. – 2009. – No. 2. – pp. 75-78. Novokshonov A.A., Sokolova N.V., Berezhkova T.V., Sakharova A.A. Clinical effectiveness of the probiotic “Acipol” in the complex therapy of acute intestinal infections of bacterial, viral and viral-bacterial etiology in children // Children's infections. – 2009. – No. 4. – P. 61-65. Barmina O.S., Gorelov A.V., Usenko D.V., Ardatskaya M.D. Clinical and laboratory effectiveness of the multiprobiotic drug Acipol in the complex therapy of “invasive” acute intestinal infections in children // Infectious diseases. – 2009. – T.7, No. 1. – p.76-79. Bulanova I.A. Rationale for the use of lactose-containing probiotics for acute watery diarrhea in young children. Abstract. diss. Ph.D. honey. Sci. - Arkhangelsk, 2008. - 24 p. Yurlova E.V., Grigorovich M.S., Chastoedova I.A. State of enzyme secretion function in acute intestinal infections in children against the background of probiotic correction // Questions of practical pediatrics. – 2011. – T. 6, No. 3. - With. 97–101 Feklisova L.V. The use of lactose-containing probiotics: an assessment of the long-term use of Acipol in pediatric practice // Pediatrics. – 2007. – No. 2. – P. 123-127. Oleinichenko E.V., Mitrokhin S.D., Nonikov V.E., Minaev V.I. The effectiveness of acipol in the prevention of intestinal dysbiosis during antibacterial therapy // Antibiotics and chemotherapy. – 1999. – No. 1. – P.23-25. Volodko N.A., Konstantinova A.V., Klimenko N.Yu. Comparative effectiveness of drugs with different effects on the intestinal biocenosis in patients with respiratory tuberculosis // International Journal on Immunorehabilitation. - 2010. - T. 12. No. 2. - P. 120-121. Tselipanova E.E., Shebekova V.M., Savitskaya K.I., Rusanova E.V., Matveevskaya N.S. Clinical and immunological effectiveness of Acipol in children with acute respiratory infection // Almanac of Clinical Medicine. - 2002. - No. 5. - P. 260-264. Savenkova M.S., Afanasyeva A.A. Treatment of infections: antibacterial and probiotic effects // Pediatrics. - 2008. - No. 1. - P. 38-40. Gordeets A.V., Piskunova S.L., Chernikova A.A. Optimization of ARVI therapy in children during an influenza pandemic // Children's infections. - 2011.- No. 4. -P.52-56. Kushnareva M.V., Dementyeva G.M., Feklisova L.V., Chernogor I.N. The influence of eubiotic drugs on local intestinal immunity in premature infants with infectious and inflammatory diseases. // Pediatrics. - 2003. - No. 3. - P. 11-14. Novikova V.P., Gurova M.M., Tsekh O.M. Complex treatment using probiotics based on lactobacilli in children with chronic gastroduodenitis in remission. Advanced medical technology. - St. Petersburg, 2010. - 24 p. Nikitina L.V., Kalutsky P.V., Lazarev A.I., Besedin A.V. The effectiveness of the use of a probiotic (Acipol) in the complex therapy of chronic gastroduodenitis associated with H. Pylori in children //International Journal on Immunorehabilitation. - 2010. - T. 12. No. 2. - P. 220b-220b. Revnova M. O. Efficacy of Acipol in the treatment of children with celiac disease // Pediatrics. Consilium medicum. – 2009. – No. 1. – p.58-59. Oreshko L.S., Matveeva I.I., Ivanova O.I., Prokofieva N.A., Balagaeva M.S. On the issue of the immunomodulatory effect of the drug Acipol in complex pathogenetic therapy in patients with celiac disease // Diseases of the digestive organs. – 2009.- No. 2.- P.63-65. Kryuchkova T.A. et al. Clinical effectiveness of the probiotic Acipol in children suffering from atopic deramatitis. // Scientific bulletins of BelSU. Series: Medicine. Pharmacy. 2012. No. 22 (141). Shuster A.M. et al. Possibilities for optimizing the use of probiotics in clinical practice using the example of the domestic drug Acipol®. RMJ. 2009, No. 4. Kornienko E.A., Saburova A.V. Experience with the use of the probiotic Acipol in the complex therapy of gastroduodenitis with bacterial overgrowth syndrome in the small intestine. Children's infections. 2022.-N 3.-P.46-50.

Perlamutrov Yu.N., Olkhovskaya K.B., Ivashkina N.Yu., Shuster A.M., Martyanov V.A. The influence of probiotics on the functional state of the epidermal barrier of facial skin // Bulletin of Dermatology and Venereology. - 2008. - No. 4. - P. 80-83.

4. The drug Atsipol, capsules LS-001915 has been registered in the Russian Federation since 2006, according to the State Register of Medicines of the Russian Federation. Consumer loyalty has been confirmed according to data from Mediaskop JSC, January-June 2019

When constipation is a temporary problem

The main reason for difficult defecation in infants today is considered to be functional immaturity of the body2, leading to uncoordinated work of the muscles of the anterior abdominal wall and rectal sphincters. Normally, the urge to defecate causes contraction of the abdominal muscles (pushing) and simultaneous relaxation of the muscles that close the anus. If this process is disrupted and the rectal sphincters relax late, bowel movements are impaired. Doctors call this condition infantile dyschezia, not constipation.

Diagnostic criteria for dyschezia:

• baby’s age – less than 9 months;
• the baby strains intensely (more than 10 minutes) before emptying the intestines;
• the stool remains soft, as it should be during breastfeeding or bottle feeding.

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How do probiotics affect bowel movements?

Probiotics are cultures of living beneficial bacteria. Once in the intestines, they begin to multiply, thereby restoring the balance of microflora and reducing the concentration of pathogenic microorganisms. Beneficial bacteria are involved in the processing of fiber fibers, polysaccharides, inulin and help maintain an acidic environment in the intestines, which prevents pathogenic bacteria from actively multiplying.

Probiotic microorganisms produce substances that stimulate contraction of the intestinal walls, which makes bowel movements easier.

Taking probiotics for hard stool for several weeks has a complex positive effect on the human body:

• restores the balance of intestinal microflora;
• reduces gas formation;
• protects against rotting and fermentation processes;
• increases the tone of the intestinal muscles;
• accelerates the production of folic acid and vitamin K.

Constipation in newborns due to illness

The main reasons leading to constipation vary depending on age. It is believed that impaired fecal excretion in the first month of a child’s life (newborn period) is most often associated with organic pathology, that is, diseases or conditions affecting not only intestinal functions.

Constipation in infants and infants can be a manifestation of various pathologies:

1. Neuromuscular diseases that disrupt intestinal peristalsis - congenital megacolon, spinal cord lesions, dysplasia of the nervous tissue of the intestine.
2. Anatomical defects, such as narrowing and intestinal obstruction.
3. Systemic diseases - rickets, hypothyroidism and thyrotoxicosis, Down syndrome, connective tissue diseases, etc.
4. Congenital intolerance to cow's milk protein and gluten (cereal protein).

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MODERN PROBIOTICS. ADVANTAGES AND DISADVANTAGES

Department of Gastroenterology and Dietetics. Northwestern State Medical University named after. I.I. Mechnikov.

Kondrashina Elina Aleksandrovna – candidate of medical sciences, associate professor

MODERN PROBIOTICS. ADVANTAGES AND DISADVANTAGES

Both in Russia and abroad, more and more products related to probiotics appear every year. They are actively studied and prescribed to patients with a wide variety of diseases. Thus, in a 2010 survey of American doctors, 86% of whom were gastroenterologists, 93% of respondents responded that at least some of their patients took probiotics. However, many of these remedies are very burdensome for the patient’s wallet and, moreover, are not always effective. Therefore, an important and often difficult task is to choose the most optimal probiotic for each specific patient.

Definition

The first assumption about the connection between microbes inhabiting the intestines and the spiritual and physical health of a person was first put forward back in 1907 in the works of the famous Russian scientist I.I. Mechnikov. But the term “ probiotic ” itself was first used in 1965 in the works of DM Lilly and RM Stiwell, which were devoted to the problems of correcting intestinal microflora in animals. It has been proposed as an antonym for antibiotics. In 1989, R. Fuller suggested that probiotics have a beneficial effect on the macroorganism.

In 1992, Havenaar R. et al. called probiotics viable cultures of microorganisms that are used in animals and people and have a beneficial effect on their body, improving the properties of the local intestinal microflora. Since 1995, probiotics have been classified as biotherapeutic agents (bacteria) with specific therapeutic properties that suppress the proliferation of pathogenic microorganisms on the mucous membranes of the digestive organs and urogenital tract.

Currently, in foreign literature, most authors refer to the recommendations of the World Organization of Gastroenterologists (2008, 2011). According to them, probiotics are live microorganisms that, when administered in adequate quantities, have a positive effect on the health of the host. This effect can be both local and systemic.

Often, some doctors confuse probiotics with prebiotics. Unlike probiotics, prebiotics do not contain live microorganisms. They are non-absorbable substances that have a positive effect on the human body, selectively stimulating the proliferation and functional activity of its own beneficial microflora.

In addition to probiotics and prebiotics, in the literature you can find such terms as symbiotics and synbiotics. Symbiotics are a combination of several probiotic species of bacteria (for example, ecoflor, bificol, bifidin, etc.). Synbiotics are complex preparations that include pre- and probiotics (floristin, bifiliz, kipacid, etc.).

Mechanisms of the positive effect of probiotics on the human body

The positive effect of probiotics on the human body is associated with the positive properties of the microorganisms they contain. Indeed, most of them include representatives of normal (indigenous) intestinal flora (bifidobacteria, lactobacilli, E. coli, etc.), and the presence of symbiont flora in the intestine is a necessary condition for the adequate existence of the macroorganism. The role of beneficial intestinal microflora for our body is multifaceted; miniature inhabitants of the intestine perform the following functions:

• protective, which consists in protecting the digestive tract from colonization by pathogenic and excessive opportunistic microorganisms (due to bacterial antagonism, production of bacteriocins, organic acids and polyhydric alcohols, creation of a protective microfilm on the surface of the intestinal mucosa);
• enzymatic (enzymes produced by intestinal bacteria take part in the digestion of carbohydrates and proteins, deconjugation of bile acids with the conversion of primary bile acids into secondary ones, cholesterol metabolism, modification of oxalates);
• synthetic (beneficial microflora produces vitamins B1, B2, B6, B8, B12, K, C, nicotinic, folic, pantothenic, lipoic acids, hormones, essential amino acids, antitumor protection substances, neuropeptides, P450-like cytochromes, antioxidants, etc. );
• immune, manifested in maintaining the activity of the phagocytic activity of macrophages and neutrophils, stimulating systemic and local production of secretory Ig A, modulating the Th1/Th2 response and cytokine response, destroying allergens;
• detoxification in the form of participation in the neutralization of exogenous and endogenous substrates and metabolites (nitrates, xenobiotics, histamine, mutagenic steroids, toxic products of protein metabolism: indole, skatole, phenol, etc., superoxide radicals, fecal microbial enzymes: β-glucuronidase, β-glucosidase , nitroreductases, etc.) due to their biotransformation and absorption by bifidobacteria and lactobacilli;
• regulation of absorption capacity, helping to increase the absorption of sodium and water, calcium, iron, magnesium, water, gases, vitamins D, E;
• participation in the regenerative activity of the colon mucosa (thanks to the short-chain fatty acids produced, beneficial intestinal bacteria ensure the regenerative capacity of the colon mucosa and normalize the processes of differentiation of its cellular structures).

Taking into account the diversity of the listed functions, the use of probiotics is not just a replacement therapy for deficient intestinal dysbiosis. These funds can be used to solve more complex problems; their impact on various systems of our body is multifaceted and not well studied.

According to modern ideas, the mechanisms of the positive effect of probiotics on the macroorganism include:

• suppression of pathogenic and excess conditionally pathogenic flora;
• stimulation of reproduction of representatives of indigenous flora as a result of the production of growth-stimulating factors;
• influence on metabolic processes;
• stimulation of the immune system of the macroorganism;
• antiallergic effect;
• anticarcinogenic effect;
• potentiation of the therapeutic effects of drugs (antibacterial, lipid-lowering, antihistamines, regulators of intestinal motility, etc.);
• prevention of reinfections.

Types of probiotics

Currently, probiotics are available in the form of:

• food;
• dietary supplements;
• medicines.

The number of bacteria in different probiotics varies significantly depending on the genus, type and strain of microorganisms, since their effect on the human body is not the same. Probiotic dosages are calculated in colony-forming units (CFU) - the number of viable microorganisms capable of forming colonies on agar medium. To realize therapeutic effects, the number of microbial bodies must be at least 107 in one gram or milliliter.

Probiotic foods

Products with probiotics can rightfully be considered representatives of functional nutrition, which is widely used in Japan and many other developed countries. The term “functional nutrition” was first introduced in 1989. It implies the use of food products that are intended for systematic consumption by all age groups of a healthy population in order to reduce the risk of diet-related diseases, maintain and improve health due to the presence of physiologically active food ingredients. By exerting a regulatory effect on physiological functions, biochemical reactions and psychosocial behavior of a person, these products support physical and spiritual health and reduce the risk of diseases (Shenderov B. A., 2006). The first probiotic functional food product specifically designed to preserve and restore health was a fermented milk product containing lactobacilli, which was introduced to the Japanese market in 1955.

The raw materials for the production of medical food products are most often milk mixtures fermented with bifidobacteria and lactobacilli in combination with kefir starter. Casein hydrolysis products stimulate the proliferation of bifidobacteria, promote the formation of short-chain fatty acids and other metabolites by the microflora, which reduce the intestinal pH and inhibit the growth of excess conditionally pathogenic microflora. Foreign scientists believe that effective medicinal yoghurts should contain at least 108 CFU per 1 ml. Currently, in order to prevent and treat intestinal dysbiosis, not only a wide variety of fermented milk products are produced, but also juices, cereals, pastes, confectionery products, ice cream, and infant formula. Bifidogenic factors based on fructose-oligosaccharides are used as a food additive in more than 500 traditional food products.

In our country, every year more and more products enriched with beneficial microflora appear on the consumer market. Accordingly, for obvious reasons, there is active advertising in the media. However, when talking with patients about choosing a particular fermented milk product, it is advisable to draw their attention to the timing and storage conditions. One should also take into account the fact of pasteurization, which has a detrimental effect on beneficial microflora, since the optimal temperature for the existence of representatives of normal intestinal microflora does not exceed 37 - 400 C. All kinds of flavoring additives, stabilizers, preservatives and dyes also have a negative effect on the microflora. But even if these conditions are met, it must be remembered that the therapeutic effect of probiotic functional food products is quite modest and is possible only with long-term use in patients with dysbacteriosis of exclusively nutritional origin, deficient in the content of representatives of normal microflora.

It seems much more justified to prepare fermented milk products enriched with beneficial microflora at home. For this you need milk and starter cultures containing lactobacilli, bifidobacteria, and thermophilic streptococci. This method allows for better control over the composition of the resulting probiotic product, since the patient independently adds jam, fruits, berries and milk of a certain fat content.

Probiotics – dietary supplements and medications

Depending on the time of creation and improvement, several generations of probiotics are distinguished:

I generation - classic monocomponent preparations, consisting of one strain of microorganisms - typical inhabitants of the intestines (bifidumbacterin, lactobacterin, etc.);

II generation - self-eliminating antagonists (bactisubtil, enterol, biosporin, etc.);

III generation – multicomponent preparations (symbiotics), consisting of several (from 2 to 30) strains of bacteria (Bifilong, etc.) or several types of bacteria (Linex, Bifikol, etc.);

IV generation - combined preparations (synbiotics), consisting of a strain of bacteria and ingredients that promote their growth, reproduction and metabolic activity (bifiliz, kypacid, etc.);

V generation – multicomponent combination preparations (synbiotics), consisting of several types of bacteria and ingredients that promote their growth, reproduction and metabolic activity (floristin, bifiform, etc.).

Probiotics should not be used blindly, but with mandatory consideration of all their components. To help the practitioner select probiotics depending on the microorganisms they contain, we have listed some of them in the table below.

Table

Probiotics and representatives of microflora contained in them

Depending on the technological methods used to create probiotic products, they are divided into:

• dry probiotics (bifidumbacterin, lactobacterin, colibacterin, etc.);
• liquid forms (floristin, trilact, bifidum BAG, liquid bifido- and lactobacterins, biovestin, biovestin-lacto, lactoflor, etc.);
• sorption forms (ecoflor, bifidobacterin forte, probifor, bificol forte, etc.);
• capsules with enteric coating (bifiform, linex).

Let's look at the features of each of these groups of probiotics.

Dry probiotics

Just a decade ago, dry probiotics were especially popular. These bacterial preparations contain live microorganisms, both in the form of monocultures and in various combinations, in a freeze-dried state.

Unfortunately, dry probiotics are characterized by low efficiency (Mayansky A., 1999; Zimmerman Ya. S., 2000). The lyophilization process negatively affects the beneficial properties and viability of bacteria. In dry forms, microbes are in a state of suspended animation, so they need up to 8–10 hours to enter an active state. By this time, most of them are eliminated from the intestines (especially in patients with increased intestinal motor activity). After the freeze-drying process, microbial cells lose some of the specific receptors that help them reliably attach to the intestinal mucosa. Such microorganisms have reduced antagonistic activity.

In addition, a significant part of living bacteria dies in the acidic environment of the stomach, the remaining ones are exposed to an alkaline environment, bile acids and pancreatic enzymes in the duodenum, which causes the bacterial membranes to dissolve and the sorption ability of microorganisms, which allows them to fix on the intestinal villi, to further suffer.

But even bacteria that have reached the intestine and are activated in it are not always capable of further colonization of the intestinal mucosa. Moreover, they may be foreign to the patient’s microbiocenosis. Only about a third of the administered dry biological products remain in the human intestine. Another significant drawback of probiotics in this group is the initially low titers of microorganisms contained in them. Therefore, most dry forms of probiotics are characterized by a “delayed” effect of their therapeutic activity (20–30 days or more), moreover, it is often temporary, and after the cessation of maintenance therapy, artificially introduced strains quickly disappear from the intestine and are replaced by random microflora.

In order to increase the effectiveness of therapy with dry probiotics, some authors (Novokshonov A.A. et al., 2001) suggest increasing the daily dose of drugs. However, treatment with megadoses, which consists of increasing the doses of lacto- and bifidobacterins by 1.5 - 3 times in a course of 2 weeks, poses a danger of sensitization. The fact is that laboratory strains of bacteria, especially at excessive doses, are often potential allergens. In addition, they can provoke the development of diarrhea in individuals with subcompensated lactase deficiency. Dry preparations containing E. coli can contribute to the development of not only allergic but also autoimmune reactions.

Liquid Probiotics

In liquid forms of probiotics, bacteria are in a biologically active state, fully retain their antagonistic properties towards pathogenic and conditionally pathogenic flora and are capable of colonizing the intestines within 2 hours. Accordingly, microorganisms realize their therapeutic effect faster than freeze-dried ones.

A valuable component of liquid probiotics are the waste products of bacteria - metabolites (essential amino acids, organic acids, interferon stimulants, vitamins, enzymes, peptides, bacteriocins), which are useful for both microbes and the macroorganism. They:

• reduce the pH of the intestinal contents, thereby improving the action of digestive enzymes and creating an unfavorable environment for pathogenic microbes;
• are an energy substrate for the colon epithelium;
• prevent atrophic and dystrophic processes in the intestinal mucosa;
• regulate differentiation and proliferation of intestinal epithelium;
• improve the absorption of water, gases, calcium, restoring the water-electrolyte balance in the intestinal lumen;
• modulate local immunity;
• have a local anti-inflammatory effect;
• promote the growth, reproduction and metabolic activity of intestinal microflora.

Foreign experts call metabolites of intestinal microflora postbiotics and are actively studying their potential in the treatment of inflammatory bowel diseases.

Liquid forms of probiotics can not only be taken orally, but also used for intraintestinal irrigation, local applications (for example, for stomatitis or cracked nipples), nasal instillation, rinsing and instillation.

A promising modern liquid probiotic is Floristin . It contains lactobacilli (L. acidofilus), bifidobacteria (B. longum, B. bifidum) and their metabolites. Along with other positive qualities inherent in all liquid probiotics, the special advantages of Floristin can be considered:

• a large number of microorganisms contained in it (about 109 CFU of viable and functionally active lactobacilli and bifidobacteria are found in 1 ml of this probiotic);
• the domestic origin of the pharmacopoeial strains of microorganisms contained in Floristin, which have not been subjected to any drying;
• resistance of the B. bifidum BAG strain used for the preparation of Floristin to the effects of aggressive components of gastric juice (hydrochloric acid, enzymes) and bile acids;
• absence of artificial colors, preservatives, flavoring additives, genetically modified components;
• convenient release form (bottle capacity with Floristin - 250 ml).

The survival of biologically active bifidobacteria cells was tested at the Moscow Research Institute of Experimental Microbiology. Gabrichevsky. Floristin is approved for use in children from 1 year of age. Data are emerging on its successful use in children with gastroenteritis of rotavirus etiology, post-infectious enterocolitis, and atopic dermatitis (Ryabchuk F.N., 2014, Nezabudkin S.N. et al., 2014). It should be remembered that the temperature regime for storing liquid probiotics ranges from 2 to 6 0C. This temperature ensures the preservation of a high titer of microorganisms for 3–12 months and is necessary to slow down the growth of microflora. When the ambient temperature rises to room temperature and above, bacteria are activated and produce metabolites that affect the biochemical properties of the environment, which leads to a decrease in the concentration of living microbial cells, and, consequently, a decrease in their therapeutic effect.

Sorption forms

The advantage of sorption forms is the association of microorganisms in microcolonies (20–180 living cells purified from the growing medium), which are fixed on a special sorbent carrier. Coal and carbon-mineral compounds can act as sorbents. Desorption of microorganisms occurs already in the large intestine, where they realize their effect.

Thanks to this structure, due to chemical and electrostatic forces, the interaction of bacteria with the parietal layer of the intestinal mucosa increases and their antagonistic activity increases. Survival increases when bifidumbacteria pass through the acidic environment of the stomach, and high local concentrations are created on the surface of the intestinal mucosa. Sorbent carriers adsorb and remove endo- and exotoxins, pathogenic bacteria and their metabolic products from the body, which helps accelerate the reparative process in the intestinal mucosa. The listed features of sorption forms contribute to a more rapid colonization of the intestines with the bacteria they contain compared to dry lyophilized forms of probiotics.

Enteric-coated capsules

The use of probiotics supplied in enteric capsules is also preferable to the administration of dry forms. The capsules of such drugs are coated with a special enteric coating resistant to hydrochloric acid, which protects the bacteria contained in the drug from destruction when passing through the stomach. As the name suggests, this capsule dissolves in the small intestine, where the microorganisms contained in the preparations are released unchanged without reducing their initial titer. In addition, the capsular shell of some probiotics contains a special nutrient medium necessary for the growth and reproduction of lactic acid bacteria.

Indications for prescribing probiotics

Most Russian specialists invariably associate probiotics with intestinal dysbiosis. Meanwhile, taking into account the various mechanisms of the positive effect of probiotics on the human body, foreign researchers are seriously studying the effectiveness of bacterial preparations in a wide variety of pathological conditions of intestinal and extraintestinal localization.

Thus, there is quite convincing data (Lee MC et al., 2001; Allen SJ et al., 2004; Sazawal S. et al., 2006) on the effectiveness of the use of probiotic strains, including L. reuteri ATCC 55730, L. rhamnosus GG, L casei DN-114 001 and Saccharomyces cerevisidae (boulardii), in children with acute infectious diarrhea. Their use reduced the severity and duration of diarrhea by approximately 1 day. The effectiveness of the use of these probiotic strains of microorganisms in viral gastroenteritis was more convincing compared to bacterial or parasitic infection. There is also evidence of the effectiveness of the use of these same strains for the prevention of acute diarrhea in children and adults.

For antibiotic-associated diarrhea, a positive effect in children and adults was observed with the administration of S. boulardii or L. rhamnosus GG. Research by Plummer S. et al. (2004), Hickson M. et al. (2007) showed the effectiveness of L. casei DN-114 001 in hospitalized adult patients in the prevention of antibiotic-associated diarrhea and diarrhea caused by C. difficile.

According to Isolauri E. et al. (2002) the therapeutic effect of probiotics in inflammatory bowel diseases is multifaceted. It is due to the fact that the introduced bacteria stabilize the immunological barrier of the intestinal mucosa, reducing the local production of pro-inflammatory cytokines, have antagonistic activity towards an unknown bacterium that causes inflammatory bowel diseases, produce antimicrobial substances, promote the restoration processes of the colon mucosa and affect pH intestinal environment. However, often this information is still contradictory and requires further in-depth study.

The use of probiotics containing lactobacilli as one of the drugs used for the eradication of Helicobacter pylori also seems promising. Lactobacilli are not only resistant to most antibiotics used in eradication regimens, but also, due to their antagonistic activity, contribute to the elimination of Helicobacter pylori, while simultaneously having a positive effect on the intestinal microbiocenosis and preventing the side effects of antibiotic therapy ( Kabir AM . 1997; Coconnier M.-H. et al .,1998; Sgouras D. et al., 2004; Sheu B.-S. et al., 2006; Tong JL et al., 2007).

Lactase deficiency (primary or secondary) is currently a problem for 70% of the world's population. These individuals have low levels of intestinal β-galactosidase activity. In this case, lactose acts as an indigestible, osmotically active carbohydrate ( Roberfroid M., 2000). Administration of probiotics containing Streptococcus thermophilus and Lactobacillus delbrueckii bulgaricus, according to Sanders ME (1993), Montalto M. et al. (2006) improves the enzymatic activity of intestinal microorganisms and, accordingly, increases the digestion of lactose, reduces the symptoms of lactase deficiency, slowing down the transit of contents through the digestive tract.

Evidence is accumulating on the use of certain probiotics for the prevention of atopic dermatitis. Thus, in their study, Osborn DA and Sinn JK (2007) showed the effectiveness of prescribing probiotics to pregnant women and newborns under 6 months of age.

There is evidence that some strains of probiotics and prebiotic oligofructose have immunostimulating effects (Schumann C. et al., 2002). Indirect evidence of this was obtained in studies aimed at preventing acute infectious diseases (nosocomial diarrhea in children, influenza), as well as in studies assessing the antibody response to vaccines.

It is assumed that probiotics reduce the duration of acute respiratory infections ( Lenoir-Wijnkoop I, 2007) , sensitivity to pain ( Konturek PC, 2011) , and increase the effectiveness of other drugs for bacterial vaginosis ( Senok AC, 2009) .

The problem of low effectiveness and side effects of probiotics

Unfortunately, probiotics do not always demonstrate sufficient effectiveness. Often the lack of the expected result is due to insufficient examination of patients. Thus, doctors often attribute all the patient’s problems to intestinal dysbiosis, forgetting about more serious diseases hiding under its mask and requiring a different therapeutic approach.

In other cases, bifido- and lactose-containing drugs are prescribed “blindly”, without first destroying opportunistic bacteria. The latter occupy all free adhesion sites on the mucous membranes, so the microorganisms introduced as part of the probiotic simply have nowhere to colonize. Some patients (for example, those with severe intestinal dysbiosis) require longer treatment than that indicated in the instructions, creating large concentrations of microorganisms in the intestines.

In addition, it should be taken into account that in the intestines of a healthy person various types of bifidobacteria, lactobacilli, and Escherichia coli are found, and the individual predominance of different strains in different patients is a proven fact. Therefore, it would be optimal to first determine in vitro the dominant strains of one or another type of normal microflora and their biocompatibility with the strains of probiotic microorganisms, and only then carry out treatment with probiotics selected in this way. Otherwise, the implanted strains of beneficial microflora may be genetically and phenotypically foreign to a given patient and have competitive antagonism to his normal microflora.

Unfortunately, there are no ideal drugs. The lack of description of side effects and contraindications for the use of a drug or dietary supplement only demonstrates the fact that this drug has not been thoroughly studied. Any probiotic can provoke the phenomenon of individual intolerance. Bacterial preparations with lactobacilli may be poorly tolerated by patients with lactase deficiency and allergies to cow's milk protein.

Moreover, some drugs contain strains of bacteria (for example, enterococci) with the potential ability to cause purulent-inflammatory processes in a weakened body. Moreover, according to some data (Shenderov B.A., 2001; Saarela M. et al., 2002), with long-term intake of live probiotic microorganisms, various complications began to be identified (laccidemia in infants, autoimmune diseases, allergic manifestations, opportunistic infections, dysbiotic conditions caused by the administration of large doses of probiotic drugs, etc.). A meta-analysis of 72 publications on the clinical use of probiotics confirmed the possibility of the development of associated bacteremia. Risk factors for this side effect were the presence of a central venous catheter, severe immunodeficiency and short bowel syndrome (Whelan K., 2010).

Requirements for modern probiotics

The effectiveness of treatment with probiotics and their tolerability largely depend on the choice of drug. A modern probiotic product must meet a number of requirements listed below:

• natural origin;
• safety during long-term use;
• resistance to hydrochloric acid and bile;
• preservation of microorganisms in an adequate dose by the end of the probiotic shelf life;
• high colonization potential of bacteria;
• effectiveness proven in controlled clinical trials;
• The microorganisms included in the probiotic must be isolated from healthy donors and be geno- and phenotypically classified.

List of used literature

1. Baranovsky A.Yu., Kondrashina E.A. Intestinal dysbiosis. - St. Petersburg: Peter, - 2007. - 240 p.
2. 2. Nezabudkin S.N., Nezabudkina A.S., Antonova T.I. The role of probiotics in the treatment of atopic dermatitis in young children with intestinal dysbiosis syndrome. – St. Petersburg. – 2014. – p.
3. Ryabchuk F.N. Modern liquid symbiotics and synbiotics in the correction of microbiocenosis in acute and chronic diseases of the digestive system. – St. Petersburg. - 2014. - 42 p.
4. Shenderov B. A. State and prospects of the concept of “Functional nutrition” in Russia: general and isolated sections of the problem // Pharmateka. – 2006. – No. 1. – P. 41 – 47.
5. Allen SJ, Okoko B., Martinez E., Gregorio G., Dans LF Probiotics for treating infectious diarrhea // Cochrane Database Syst Rev. – 2004. – No. 2. - CD003048.
6. Guarner F., Khan AG, Garisch J.et al. World gastroenterology organization global guidelines: probiotics and prebiotics // J Clin Gastroenterol. – 2012. – V. 46(6). – P.468-481.
7. Hickson M., D'Souza AL, Muthu N. et al. Use of probiotic Lactobacillus preparation to prevent diarrhoea associated with antibiotics: randomized double blind placebo controlled trial // BMJ - 2007. - V.335. – P. 7610:80.
8. https://nccam.nih.gov/health/probiotics/introduction.htm. Updated November 2011. Accessed July 24, 2012.
9. Konturek PC, Brzozowski T., Konturek SJ Stress and the gut: pathophysiology, clinical consequences, diagnostic approach and treatment options // J Physiol Pharmacol. – 2011. V.62(6). – P.591-599.

10. Lee MC, Lin LH, Hung KL, Wu HY Oral bacterial therapy promotes recovery from acute diarrhea in children // Acta Paediatr Taiwan - 2001. - V. 42. - P. 301–305.

11. Montalto M., Curigliano V., Santoro L., et al. Management and treatment of lactose malabsorption // World J Gastroenterol - 2006. - V.12. – P.187–191.

12. Plummer S, Weaver MA, Harris JC et al. Clostridium difficile pilot study: effects of probiotic supplementation on the incidence of Clostridium difficile diarrhea // Int Microbiol – 2004. – V.7. – P.59–62.

13. Roberfroid MB Global view on functional foods: European perspectives // Br J Nutrition - 2002. - V. 88 (suppl. 2). – P.133-138.

14. Saavedra JM Clinical applications of probiotic agents // Am. J. Clin. Nutr. - 2001. - V. 73(6). —P. 1147S—1151S.

15. Schumann C. Medical, nutritional and technological properties of lactulose // Eur J Nutr – 2002. – V. 41(Suppl 1). – P. 17–25

16. Tong JL, Ran ZH, Shen J., Zhang CX, Xiao SD Meta-analysis: the effect of supplementation with probiotics on eradication rates and adverse events during Helicobacter pylori eradication therapy // Aliment Pharmacol Ther - 2007. - V. 25 . – P.155–168.

17. Whelan K., Myers CE Safety of probiotics in patients receiving nutritional support: a systematic review of case reports, randomized controlled trials, and nonrandomized trials // Am J Clinc Nutr. – 2010. V. 91(3). – P. 687-703.

18.Williams MD, Ha CY, Ciorba MA Probiotics as therapy in gastroenterology: a study of physician opinions and recommendations //J Clin Gastroenterol. – 2010. – V. 44(9). – P. 631-636.

Functional constipation in infants of the first year of life

In the vast majority of cases, constipation in young children is associated with temporary disturbances in intestinal motility as a result of nutritional defects in the nursing mother or the baby itself 1,2.

Nutritional, that is, nutrition-related causes of constipation in newborns and infants1:

• underfeeding, leading to a decrease in volume and compaction of stool;
• improper nutrition of a nursing mother, in particular the abuse of “strengthening” products containing little coarse fiber;
• Stopping breastfeeding and switching to artificial feeding;
• insufficient fluid intake into the child’s body, especially if he is on artificial nutrition or receiving complementary foods;
• quick, in less than 3 days, transition from one mixture to another;
• use of unadapted products for feeding, for example, cow's or goat's milk;
• introduction of foods low in dietary fiber as complementary foods, for example, semolina porridge.

The situation is aggravated by the baby’s low physical activity, the mother’s excessive persistence and haste in potty training and, in particular, the frequent irrational use of a gas tube, enemas and irritating laxatives to empty the rectum1,2.

Up to contents

Causes of constipation

Consider your answers to the questions below:

• Is the child getting enough food? If not, then feces are not formed in sufficient volume, and this leads to a lack of stool.
• Have you chosen the right formula if your baby is bottle-fed?
• When and how was complementary feeding introduced? Intestinal problems can be an individual reaction to a new product due to early or improper complementary feeding2.
• Does the baby get enough vegetables and fruits during the introduction of complementary foods? It is important to introduce foods containing fiber in a timely manner, as it is necessary for normal digestion5,8.
• Is there enough vegetables and fruits in a nursing mother's diet? The cause of constipation in a baby may be their deficiency, as well as the mother’s excessive consumption of protein foods and flour products5,8.
• Does the child have enough fluids that he consumes? After all, its deficiency can cause constipation in infants both breastfed and bottle-fed5,8.
• Does the baby have any disease that causes constipation as one of the symptoms, such as rickets or hypothyroidism (rickets is insufficient bone mineralization associated with a lack of vitamin D, and hypothyroidism is a low level of thyroid hormone production)3? If the thyroid gland does not produce the required amount of hormones or the child’s body does not respond to these hormones, the development of organs and systems, including the gastrointestinal tract, slows down4. Rickets, a so-called growth disease, can also cause constipation in infants due to slow metabolism and bone deformation4.
• Does the baby have bowel abnormalities? With increased or insufficient motor activity of the intestines, the rhythm, quantity or quality of muscle contractions is disrupted3.
• Does he have lactase deficiency, that is, a lack of the enzyme necessary to break down the milk sugar lactose? In this case, constipation most often alternates with diarrhea8.

The most common causes of constipation in infants:

• pathologies of development of the gastrointestinal tract (GIT);
• diseases of the endocrine system;
• psychogenic disorders;
• intestinal dysbiosis5.

Anomalies in the development of the gastrointestinal tract can only be detected with the help of comprehensive, timely diagnostics. In addition, constipation in infants can be inherited. If one of the parents himself encountered them in infancy, there is a high probability that the cause of constipation in the infant is hereditary4.

Psychogenic or stress constipation in breastfed infants may occur as a reaction to weaning4.

A sudden attempt to replace breast milk with artificial formula or vegetable puree can completely “confuse” the baby’s digestion6.

A similar situation can arise in older children due to sitting on the potty against the child’s will. If this procedure is psychologically inconvenient for the child, he will avoid bowel movements until the last minute, ignoring the urge. During this time, stool accumulates in the rectum, increases in diameter and becomes harder. Later, when the child decides to go potty, the process of bowel movement can cause pain. In the future, the child may be afraid to feel pain again, which will make the situation even worse6.

In sedentary children, slow intestinal motility may be observed. If a child, instead of exploring the world and space around him, prefers to sit or lie lazily, then his digestive system also begins to become “lazy.” This is also one of the causes of constipation in newborns and older children with mixed feeding5,8. Duphalac® can help improve intestinal motility in babies.

In addition, constipation in breastfed and bottle-fed infants may be a consequence of an imbalance in the intestinal microflora. Due to an insufficient number of beneficial bacteria, the microflora does not have time to perform its functions of decomposing feces. At the same time, dysbiosis itself occurs in children for many reasons. This may include late breastfeeding, complete artificial feeding, chronic gastrointestinal diseases, poor nutrition of the mother or baby, as well as lactose intolerance9.

Dysbacteriosis can also cause constipation in newborns8. Duphalac®, in addition to treating constipation, helps restore intestinal microflora thanks to its prebiotic effect7.

Microbiological aspects in the treatment of constipation

The development of all higher organisms was carried out in the presence of bacteria, one of the oldest forms of life on Earth, which led to the closest connections between them [14]. Therefore, all body tissues in contact with the external environment are habitat niches for a wide range of microorganisms that form biological films. The quantitative and qualitative composition of microbial associations is controlled, on the one hand, by the “quorum sensing” system, which allows bacteria to exchange information through the diffusion of signaling molecules that regulate the expression of bacterial genes when achieving optimal cell density [2], on the other hand, the host tissues of the macroorganism have the ability to optimize microbial ecosystems through the production of antimicrobial peptides [14]. The complexity of these relationships is complemented by the influence of microorganisms on the functioning of the organ-environment in a manner favorable to themselves, through the expression of messenger molecules for various intercellular signaling pathways of the macroorganism, and the correct maturation of the human immune system is largely mediated by the influence of representatives of its microflora [29].

The composition of the microflora of each person is individual, like fingerprints [3], and this individuality can be explained by the characteristics of immune reactions, feeding, lifestyle, past infections and means of treatment, as well as existing chronic pathology [7, 32]. A decrease in the activity of intestinal motor function, manifested by constipation, also has a significant effect on the composition and topology of the intestinal microflora [10]. Food debris that is not removed in time can serve as a substrate for individual microorganisms and is an important advantage in the competitive struggle of bacteria. In addition, regular use of laxatives and enemas by patients with constipation may also affect the composition of the intestinal microflora. Thus, adult patients with constipation are characterized by a decrease in the number of bifidobacteria and lactobacilli with an increase in Veillionella species [10], while children are characterized by an increase in the number of clostridia and bifidobacteria [19, 24]. In some studies, a course of antibiotic therapy increased stool frequency, improved stool consistency, and eliminated straining, which confirmed the role of microflora changes in the formation of constipation [24].

Some light on the mechanism of the connection between intestinal flora and constipation can be shed by studies in which, in patients with irritable bowel syndrome (IBS) with constipation, a hydrogen breath test with lactulose revealed a significant increase in methane production, associated with an increase in intestinal transit time [23]. Under experimental conditions, methane inhibited the motor function of the intestine by increasing its tone [23]. Moreover, it should be emphasized that the source of excess amounts of methane in the exhaled air of patients with constipation has not yet been determined and some researchers believe that they are methane-forming bacteria of the colon, not the small intestine [24]. Thus, therapeutic measures aimed at correcting the microbial composition in patients with constipation can help restore intestinal transit time and maintain a state of remission for this indicator.

Treatment of chronic constipation should be carried out in conditions of lifestyle correction with the obligatory elimination of factors contributing to stool retention. To achieve success in a large proportion of patients, it is enough just to provide an immediate response to the onset of urge and restore the bowel habits during the day and in relation to meals [6]. Increasing the level of physical activity may help in cases of mild constipation, but in the case of prolonged absence of stool, this measure is ineffective [6]. Increasing fluid intake does not have a significant effect on the rate of intestinal transit and in the absence of signs of dehydration this recommendation is ineffective [6].

Dietary fiber has been used in the treatment of constipation for about 500 years and is overwhelmingly non-starch polysaccharides. Water-soluble fibers (pectin, gums and mucus) are able to form viscous solutions and retain water in the intestinal contents, increasing its volume and having little effect on transit time, insoluble fibers (cellulose, hemicellulose and lignins) are not able to retain water, but significantly increase the volume of stool and significantly stimulate intestinal transit [6, 24]. The inverse relationship between dietary fiber solubility and increased stool weight is explained by the greater susceptibility of soluble fiber to bacterial fermentation in the proximal colon. The laxative effect of dietary fiber is provided by the swelling of undigested fiber, fluid retention in the intestinal contents, the prokinetic effect of bacterial fermentation products (butyrate), stimulation of the growth of bacterial mass (which represents the dry mass of feces), increased production of gases and other by-products of fermentation that increase stool weight [24]. ]. In healthy volunteers, the effect of 25 g fiber on stool weight varied widely, from +17–19% with pectin and gums to +117% with bran [24]. As is known, some patients with constipation are resistant to the laxative effect of dietary fiber, and this resistance turned out to be directly proportional to the increase in intestinal transit time [24]. Recommendations to increase fiber content to 10–20 g per 1000 kcal of diet [6] are extremely common, but their evidence base is weak: modern systematic reviews describe the effect of fiber on stool frequency as modest at best, with an effect in placebo-controlled studies soluble fiber (psyllium) on stool frequency and consistency was described as positive, while bran failed to demonstrate a significant positive effect in similar conditions [24]. The lack of large, well-designed studies on the use of dietary fiber in the treatment of constipation limits its use in risk groups such as elderly patients and patients with neurological diseases. Although high-fiber foods and medications are free of serious side effects, their palatability (especially bran) and tolerability issues due to fermentation and gas production are major barriers to their use in IBS patients with constipation, who often associate the presence of symptoms with food intake, since the inclusion of insoluble fibers can provoke pain [24]. Adjusting the proportions between soluble and insoluble fibers may help overcome the problem of intolerance in these patients [6]. Based on a generalization of application experience, we can conclude that biologically active supplements (BAA) and food products containing dietary fiber are effective in patients with chronic constipation without delayed transit and pelvic floor dyssynergia, and in this group their effectiveness reaches 80% [6] .

Prebiotics are fermentable foods that exert their beneficial effects on the health of the host by selectively stimulating the proliferation and activity of certain types of bacteria in the colon. Of the prebiotics, only inulin and fructooligosaccharides have sufficient evidence for their use as ingredients in functional foods; they are fermented in the colon to produce energy and end products such as lactic acid and short-chain fatty acids [24]. It should be borne in mind that dietary fiber and lactulose, widely used for constipation, also have prebiotic properties. There are very few studies in the literature on the effect of prebiotics on stool retention with a satisfactory design, and when interpreting the results obtained, the influence on the microflora from food ingredients should be taken into account, since polymeric carbohydrates with prebiotic properties are widely distributed in fruits, vegetables and cereals [6] .

Relatively recently, in addition to pathogenic and fermenting bacteria, human symbiotic microorganisms came into the sphere of interest of microbiologists, when the significant influence of these microorganisms, especially intestinal microflora, on the health of the host organism was established, which contributed to the formation of the concept of probiotics. I. I. Mechnikov was the first to formulate this idea, believing that lactic acid bacteria are the most suitable candidates for the role of probiotic microorganisms. But during the heyday of antibiotics and vaccines, this idea did not receive due attention, and only the emergence of multi-resistant strains and awareness of the role of human microflora in maintaining health contributed to a surge of interest in this concept. A working group of the World Health Organization in 2002 adopted a definition of probiotics as “live microorganisms that, when administered in adequate quantities, contribute to improving the health of the host” [31].

The bulk of probiotic products currently on the market belong to a large group of lactic acid bacteria, which are normal representatives of the microflora of the human gastrointestinal tract (Table 1) [22]. However, numerous researchers are exploring the potential probiotic capabilities of other microorganisms, such as yeast, that are not normally present in the human intestine [25].

Probiotic strains exert their health benefits through multiple mechanisms unique to each strain (Table 2) [22], and the interaction space between the probiotic and the host can be divided into three levels: 1) the intestinal lumen, 2) the intestinal epithelium, and 3) immune system [27]. However, the mechanisms for implementing a significant part of the described effects of probiotics have not been fully disclosed.

It has now become known that probiotic bacteria are able to interact with the cells of the host organism by interfering with the functioning of intercellular signal transmission pathways [22]. Secreted bacterial products (peptides, short-chain fatty acids, bacteriocins, nitric oxide) [12, 18, 30, 31] and structural components of dead bacteria (DNA, proteins, lipopolysaccharides) [5] are capable of causing a specific response from the human body, for example, altering the activity of the transcription factors NF-kB and AP-1 either through mitogen-activated protein kinases (MAPKs) or protein kinase C and phosphatidyl-inositol 3-kinase [22, 28].

Gram-positive bacteria use N-acyl-homoserine lactones and 2-alkyl-4-quinolones as signal molecules, while Gram-negative bacteria use peptides capable of forming cyclic structures that ensure the functioning of the “quorum sensing” system [2]. Some of these molecules interact with cell surface receptors, others have receptors intracellularly, and some of these molecules have recently been shown to have immunomodulatory properties [33].

In relation to constipation, there are several clinical studies in which probiotics (sometimes in combination with a prebiotic) have been shown to speed up intestinal transit in patients with slow transit. Thus, Bifidobacterium animalis reduced intestinal transit in healthy women, elderly patients and patients with IBS [24]. This effect was observed only when using live microorganisms and was more pronounced in individuals with an initially pronounced slowdown in transit. In individuals with IBS, this acceleration of transit was most pronounced in the right side of the colon, which contains the highest density of bacterial contents [24]. Upon closer examination, the acceleration of transit was found to be independent of changes in fecal mass and bile acid content, implying a direct effect of the probiotic on intestinal motility [24]. Other researchers were able to prove the ability of a combination of Lactobacillus ramnosus, B. lactis and inulin to stimulate the motor function of the small intestine [24]. Another way probiotics influence the functional activity of the intestine may be mediated by the central nervous system. The connection between anxiety and depressive disorders and disorders of intestinal motor function has now become indisputable, and the presence of constipation in a patient always requires the exclusion of emotional disorders [15]. Animal studies have found that the introduction of Bifidobacteria infantis into the diet of rats for 14 days contributed to a significant increase in the level of tryptophan in the blood plasma, which is a precursor of neurotransmitters (serotonin) in brain cells, which was regarded by the authors as the presence of antidepressant potential in these bacteria [10, 13].

Among the published data from randomized controlled trials, a positive effect in patients with chronic constipation (without the presence of IBS) was noted when using a probiotic drink containing Lactobacillus casei Shirota, as well as the probiotic strain B. lactis DN-173010 [6]. In children with functional constipation, under placebo-controlled conditions, administration of L. reuteri significantly increased stool frequency, but without a significant change in stool consistency [11]. Normalization of bowel movements in nursing home patients has been achieved using B. longum [6]. Other studies with less rigorous designs or combinations of probiotics and other treatments have shown encouraging results for bifidobacteria, lactobacilli, propionobacteria, and fecal suspension infusions [17, 24]. In a meta-analysis of the effectiveness of probiotics for constipation, including five studies with 377 participants, a positive effect on stool frequency and consistency was obtained with the use of B. lactis DN-173010, L. casei Shirota and Escherichia coli Nissle 1917 [9].

Strong support for the concept of using probiotics for stool retention comes from studies on IBS [16]. Bifidobacterium animalis, in addition to reducing intestinal transit time, significantly increased stool frequency in patients with IBS with constipation. Another strain of B. infantis 35624 was able to normalize stool consistency and reduce the need to strain in patients with IBS, without significantly changing stool frequency [21].

Recent reviews [6, 25] have emphasized the fact that administration of L. rhamnosus GG has been found to be ineffective when used in patients with constipation. These studies refer to a placebo-controlled study by Polish researchers [4], who found no additional effect on stool parameters when adding this probiotic to a lactulose treatment regimen in a pediatric population (n = 84). While in earlier work involving adult patients with constipation, L. rhamnosus GG showed a positive effect on stool count [20]. Possible reasons for the lack of effectiveness of this strain in children may be some errors in the study design: patients received the probiotic in the form of capsules, and they were allowed to open them and add the contents to food (knowing the dislike of children for tablets and capsules, it can be assumed that most children opened them — this indicator, unfortunately, was not taken into account in the study). As it became known relatively recently [26], the effectiveness of a probiotic strongly depends on the fat content, the concentration and type of protein and monodisaccharides, as well as the pH of the carrier medium. Fermented milk drinks, where these parameters are most successfully balanced, are recognized as the optimal means of probiotic delivery. Also, the researchers absolutely did not take into account the composition and quantity of food eaten, which could have a decisive influence on the frequency and consistency of stool.

As an alternative point of view, we can refer to our study performed two years ago [1]. The study included 60 inpatients with IBS with constipation (Rome III criteria), who were randomized into three groups similar in age, presence of underlying and concomitant diseases. In group 1, the diet was modified by replacing kefir and sour cream with 330 g of the studied drinking yogurt Bio Balance®, enriched with bifidobacteria and L. rhamnosus GG (ATCC 53103, LGG®), with a CFU content at the end of the shelf life of at least: bifidobacteria - 106 , lactobacilli - 107. The basic diet of patients of the 2nd group is modified by replacing kefir and sour cream with 330 ml of Bio Balance® kefir drink, enriched with probiotics according to a similar scheme, with a CFU content at the end of the shelf life of at least: bifidobacteria - 106, lactobacilli - 106. The control group consisted of patients who received a standard diet with traditional fermented milk products. It is worth noting that the consumption of homemade products is not allowed by the Clinic's rules, so the differences in the diets of the participants were minimal. The duration of the clinical trial was 21 days. The groups were compared in terms of the dynamics of quality of life and severity of complaints, in terms of stool consistency indicators indicating its frequency, and microbiological analysis data. Patients noted greater satisfaction with the quality of bowel movements, and it is worth noting that in the group that consumed fortified yoghurts and kefir drink Bio Balance®, better dynamics of this complaint were noted (-1.1 on a 5-point Likert scale, p = 0.01) than in patients of the control group (-0.45 at p = 0.05). Only in the group that consumed the studied yogurt and kefir drink Bio Balance®, there was a significant improvement in stool consistency (+0.95, p = 0.01 and +0.68, p = 0.01 Bristol stool scale), an increase in stool frequency was more pronounced than in the control group (+0.24 times/day, p = 0.05 versus +0.13 times/day, p = 0.05). The differences in the dynamics of quality of life indicators between the groups were insignificant. Only in patients who received the studied kefir drink Bio Balance®, a significant increase in both lacto- (+2.2 lg) and bifidobacteria (+1.7 lg) was observed; in patients who received fortified yogurt Bio Balance®, only growth of lactobacilli (+3.1 lg), and in the control group at the end of the observation period there was an increase in the content of bifidobacteria (+2.7 lg), which emphasizes the connection between changes in the clinical picture and the activity of the probiotic.

Thus, the exclusion of L. rhamnosus GG (ATCC 53103, LGG®) from the list of probiotic microorganisms effective for constipation seems premature and requires studies with a more reliable design.

Conclusion

Chronic constipation is an extremely common disease worldwide that can seriously impair the quality of life of both adults and children. Only 60% of patients with constipation are satisfied with the effectiveness of laxatives, and a significant proportion of them require long-term maintenance treatment [11]. The widespread use of dietary fiber in people with chronic constipation or IBS sometimes leads to discouraging results: insoluble dietary fiber, despite the most pronounced effect on stool frequency, may be contraindicated in patients with IBS due to increased bloating and abdominal pain. The unconditional importance of intestinal microflora for the normal functioning of the small and, especially, large intestine in the presence of changes in the microbial landscape in people with constipation provides sufficient grounds for the use of pro- and prebiotics in the treatment of chronic constipation and IBS. It seems very attractive the idea of ​​widespread use by various segments of the population of food products enriched with effective probiotic strains for the treatment and prevention of stool retention, which is accurately reflected in the words of the great Hippocrates: “let my food become medicine...”, and, it should be noted, a safe medicine! To determine the most optimal strain and type of probiotic in a sufficient dose for each variant of chronic stool retention, as well as the selection of a carrier medium, it is necessary to conduct high-quality studies in design involving a large number of patients.

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V. I. Pilipenko, Candidate of Medical Sciences D. A. Teplyuk A. K. Shakhovskaya, Candidate of Medical Sciences V. A. Isakov, Doctor of Medical Sciences, Professor of the Research Institute of Nutrition of the Russian Academy of Medical Sciences, Moscow

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