Научная статья на тему 'Impact of a High-Fat and High-Fiber Diet on Gut Microbiota in ICR (CD1) Mice'

Impact of a High-Fat and High-Fiber Diet on Gut Microbiota in ICR (CD1) Mice Текст научной статьи по специальности «Биологические науки»

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Opera Medica et Physiologica
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yeasts / enterobacteria / lactobacilli / bifidobacteria.

Аннотация научной статьи по биологическим наукам, автор научной работы — V.A. Shepilova, A.S. Krivenko, N.V. Ivanova, A.V. Kabachkova, O.P. Ikkert

This study evaluated the effect of different diets on the probiotic (lacto-, bifidobacteria) and opportunistic (yeast, Escherichia coli) intestinal microflora of CD1 mice. The high-fat diet contained 40% animal fat (lard) and the high-fiber diet contained 40% freeze-dried fiber. The intestinal microflora was determined by the standard method of seeding the contents of the intestine on selective culture media (MPС, Blaurock, Sabouraud, Endo). The results showed that on the 50th day of the experiment in the group of mice with a high fat content, the population of probiotic cultures of lactoand bifidobacteria decreased, while the population of yeast and enterobacteria increased, compared with the starting point of the experiment and the control group of mice. The weight of mice in this group by the end of the experiment increased by 16%. In the group of mice with a high content of insoluble fiber, a decrease in the populations of probiotic cultures, yeasts and enterobacteria was observed. At the same time, the weight of mice increased by 13.6%. Thus, high fat intake in the diet entails possible disturbances in the intestinal microbiota, an increase in opportunistic microflora, which can lead to intestinal diseases. When using a large amount of insoluble fiber, on the contrary, it leads to a decrease in microflora in general. This is most likely due to a lack of nutrients and enough nutrients (proteins and fats) in the diet, which are still necessary for the microflora.

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Текст научной работы на тему «Impact of a High-Fat and High-Fiber Diet on Gut Microbiota in ICR (CD1) Mice»

IMPACT OF A HIGH-FAT AND HIGH-FIBER DIET ON GUT MICROBIOTA IN ICR (CD1) MICE

V.A. Shepilova1'2*, A.S. Krivenko2, N.V. Ivanova2, A.V. Kabachkova1, O.P. Ikkert1-2

1 National Research Tomsk State University, 36 Lenin Ave., Tomsk, 634050, Russia;

2 Tomsk Agricultural Institute - branch of Novosibirsk State Agrarian University, 19 K. Marx St., Tomsk, 634050, Russia.

* Corresponding author: [email protected]

Abstract. This study evaluated the effect of different diets on the probiotic (lacto-, bifidobacteria) and opportunistic (yeast, Escherichia coli) intestinal microflora of CD1 mice. The high-fat diet contained 40% animal fat (lard) and the high-fiber diet contained 40% freeze-dried fiber. The intestinal microflora was determined by the standard method of seeding the contents of the intestine on selective culture media (MPC, Blaurock, Sabouraud, Endo). The results showed that on the 50th day of the experiment in the group of mice with a high fat content, the population of probiotic cultures of lacto- and bifidobacteria decreased, while the population of yeast and enterobacteria increased, compared with the starting point of the experiment and the control group of mice. The weight of mice in this group by the end of the experiment increased by 16%. In the group of mice with a high content of insoluble fiber, a decrease in the populations of probiotic cultures, yeasts and enterobacteria was observed. At the same time, the weight of mice increased by 13.6%. Thus, high fat intake in the diet entails possible disturbances in the intestinal microbiota, an increase in opportunistic microflora, which can lead to intestinal diseases. When using a large amount of insoluble fiber, on the contrary, it leads to a decrease in microflora in general. This is most likely due to a lack of nutrients and enough nutrients (proteins and fats) in the diet, which are still necessary for the microflora.

Keywords: yeasts, enterobacteria, lactobacilli, bifidobacteria.

List of Abbreviations

ATP - Adenosine triphosphate CFU - colony-forming units MPC - Milk Proteins Concentrate SCFAs - short-chain fatty acids

Introduction

The gut microbiota is a complex dynamic system (Romanchuk, 2020). The versatility of the relationships of the gut microbiota, both with the host organism and within the microbial community itself, gives researchers reason to separate the microbiota into a separate physiological system (Yudina et al., 2019) or consider it as a «new organ» (Mallick, 2017). Numerous studies show a close relationship between the violation of the intestinal microflora and the manifestation of the metabolic syndrome (Croci et al., 2021), the development of type 2 diabetes (Meijnikman et al., 2018), atherosclerosis (Af-ineevskaya et al., 2020), colon cancer (Kochkina et al., 2019), and neurodegenerative diseases of the brain (Sun et al., 2021). Along with this, the existence of a relationship between the state of the intestinal microbiota, the central nervous system, and complex emotional

behavior has been shown (Foster et al., 2016; Sudo, 2016). This relationship has been described as a gut-brain axis in which the micro-biome plays a key role (Foster, 2013) (Fig. 1). Thus, studies on the study of possible ways of influencing the intestinal microbiome are becoming relevant and promising. Diet is one of the powerful adaptive mechanisms and promotes the integration of the body into a specific environment (Romanchuk, 2020).

Objective: to conduct a comparative analysis of the effect of different diets (high-fat and high-fiber) on changes in the gut microbiota in ICR (CD1) mice.

Materials and Methods

Ethical Approval

The study was carried out in compliance with the principles of the European Convention for the Protection of Vertebrate Animals used for Experiments and Other Scientific Purposes (Strasbourg, 1986) in accordance with the rules of proper laboratory practice (Moscow, 2016), and was approved by the Ethics Committee of National research Tomsk State University.

Fig. 1. Gut-brain axis

Animals and experimental design

The studies were carried out on 15 outbred males of the ICR line (CD1) with an initial body weight of 30-35 g. Age at the beginning of the experiment was 12 weeks. The mice were obtained from the vivarium of the E. D. Goldberg Research Institute of Pharmacology and Regenerative Medicine of the Tomsk National Research Medical Center of the Russian Academy of Sciences. During the period of adaptation (14 days) and the experiment, the animals were kept under standard vivarium conditions: air temperature regime 21-24 °C, relative humidity 3070%, light regime 12:12 h, free access to water.

In the diet of the animals, food was used «Delta Feeds» C-19 (BioPro, Novosibirsk). The animals were divided into 3 groups of 5 animals in each group: 1st group (control group) - animals with a standard diet, received food for keeping laboratory animals, prepared according to GOST 34566-2019 (mass fraction of fat not more than 6%); 2nd group (high-fat group) - a diet with a high-fat content (the feed included

40% saturated fat - lard), 3rd group (high-fiber group) - a diet with a high-fiber content (the feed included 40% wheat and oat fiber (insoluble), fat content no more than 6%). The daily ration was 10 grams per laboratory animal. The duration of the study is 50 days. The amount of food eaten, and liquids drunk by each group, morbidity, mortality, appearance, physical activity, stool condition, changes in behavior were recorded daily. Mice were weighed weekly. The experimental design is shown in Figure 2.

Material selection and cultivation

Feces were taken from each individual mouse, after placing the mouse in a separate cage. The selection and inoculation of the biomaterial was carried out on days 0, 17, 34, and 50 of the experiment. Before sowing, a biomaterial suspension was obtained: 1 g of feces was crushed in 9 ml of distilled sterile water. Next, the corresponding tenfold dilutions (dilution of 10-10) of the biomaterial suspension were inoculated onto nutrient media.

Fig. 2. Experimental design

To determine viable (colony-forming units, CFU) opportunistic pathogens, selective culture media Endo Agar (BioMedia) (for the isolation of Enterobacteriaceae) (Abu-Sini et al., 2023) and Sabouraud Medium (Biotechnovation) (for the isolation of yeasts) (Di Paola et al., 2020) were used. The seeding of the biomaterial was carried out on Petri dishes, 100 pl of dilution of the suspension of the biomaterial, dilutions from 10-2 to 10-10 were used. Determination of CFU of probiotic cultures was carried out on Blaurock Medium (Bifidum-medium, Ob-olensk) (for the isolation of Bifidobacterium) (Khabirov et al., 2022) and Medium MRS agar (Obolensk) (for the isolation of Lactobacillus) (Farahmand et al., 2021). Seeding was carried out in test tubes with a volume of 10 ml, 1 ml of biomaterial suspension, dilutions from 10-2 to 10-10 were used. Cultivation was carried out at 37 °C for 1-7 days. To obtain reliable data, 3 replications of seeding were performed for each experimental point. Colonies were counted on days 1-2, 5, and 7. Determination of the morphology of microorganisms (cell shape, Gram stain, presence of spores and capsules) was carried out by phase-contrast (colony prints) and light microscopy (stained smears). The data

was represented as the CFU/g of wet weight fecal sample by applying the dilution factor. The mean and standard deviation were calculated for all the variables in the Microsoft Excel.

Results

Body weights and food intake

By the end of the experiment, mice in all groups gained weight compared to the weight at the starting point of the experiment. The maximum weight gain of mice was noted only in the high-fat group, an increase of 16.0% from the starting point of the experiment (Fig. 3A). In the high-fiber and control groups, the weight of mice also increased, by 13.6% and 12.3%, respectively. At the same time, at the beginning of the experiment, the percentage of food intake (100% was taken as the norm: 10 g of food per 1 mouse per day) in the high-fat group and high-fiber group decreased. But starting from the 15th day of the experiment in these groups, the percentage of food intake began to increase. In the control group, food intake was erratic and remained approximately the same (Fig. 3B). By the end of the experiment, the percentage of food intake increased significantly in the experimental group. The decrease in food intake at

Fig. 3. Body weight of mice and percentage of food intake in groups with different types of diets

Note: A - body weight of mice, B - percentage of food intake, solid line - recorded parameters, dotted line

- trend line (polynomial function to the 6th degree), R2 - approximation confidence factor

the beginning of the experiment can be explained by the adaptation and habituation of mice to a new food, while after adaptation food intake returned to normal.

Colony morphology

Lactobacillus colonies on MRS agar Medium were small (1-2 mm), creamy-white in color and shaped like a «grain» on days 2-3 of cultivation (Fig. 4A). During microscopy, immobile filamentous bacterial rods were observed, sometimes arranged in a chain or pair. The cell size was from 3 to 5 |im; the cells did not form spores or capsules. Gram stain showed Gram-positive bacterial cells (Fig. 4B).

Bifidobacterium colonies on Blaurock Medium on days 2-3 of cultivation were about 0.5-1 mm, disc-shaped colonies, white in color (Fig. 5A). Cells under microscopy were rod-shaped, sometimes slightly curved, 2 to 5 p,m long, cells did not form spores or capsules. Gram stain was positive (Fig. 5B).

Colonies of Enterobacteriaceae on Endo agar plates were round with smooth edges, raspberry red with a metallic sheen, glossy, 1-2 mm in size (Fig. 6A). Microscopic examination showed single shortened rods. The cell size was from 1 to 3 ^m; the cells did not form spores or capsules. Gram stain confirmed the presence of Enterobacteriaceae, which appeared as gramnegative rods (Fig. 6B).

Fig. 4. Colonies of probiotic microorganisms (Lactobacillus) on the MPS nutrient medium Note: А - six-fold dilutions, an enlarged photo of the colony of Lactobacilli, В - Lactobacillus cells isolated from colonies, Gram-stained (sample obtained from inoculation of faeces of mice from group high-fat on the 31st day of the experiment)

Fig. 5. Colonies of probiotic microorganisms (Bifidobacterium) on the Blaurock medium Note: А - three-fold dilutions, an enlarged photo of the colony of Bifidobacterium (in the light), В - Bifidobacterium cells isolated from colonies, Gram-stained (sample obtained from inoculation of faeces of mice from group high-fat on the 31st day of the experiment)

Fig. 6. Enterobacteria (E. coli) colonies on Endo medium

Note: A - Triple dilutions, enlarged photo of an E. coli colony, B - Gram-stained E. coli cells isolated from colonies (sample obtained from fecal inoculation of mice from the control group on the 50th day of the experiment)

Yeast colonies on Sabouraud's medium on days 1-2 of cultivation were larger - 2-4 mm, round, white, glossy, and slightly convex. Microscopic examination revealed large, oval, and oblong cells, ranging in size from 5 to 8 |im (Fig. 7).

Microbial colonies were counted based on the typical colony morphological features on the selective media using the BioRad Chemi-Doc MP universal system colony counter, based on VisionWorks LS software.

Enumeration of fecal Lactobacillus, Bifidobacterium, Enterobacteriaceae (Esche-richia coli) and Yeast

The results of the number of microorganisms formed on different media are presented in Table 1. Initial changes in the composition of the microbiota in the high-fat and high-fiber groups were recorded on the 17th day of the experiment and progressed until the end of the study. There was an expected statistically significant increase in Enterobacteriaceae in the groups of

and a decrease in the group with a high-fiber diet - (10.8 ± 1.91)x102 (compared to the control group - (6.25 ± 0.58)x104). A similar pattern was shown for yeast, where an increased value was observed in the high-fat group (7.28 ± 0.64)x108 and decreased values in the high-fiber group (4.45±0.84)x106. Interestingly, along with opportunistic microflora, the results show a significant reduction in Lactoba-cillus and Bifidobacterium in both experimental groups versus the control group. Moreover, for mice of the high-fiber group, a more pronounced decrease in the relative abundance of Lactobacillus in fecal samples was shown: from (6.06 ± 0.46)x107 on the first day of the experiment to (5.45 ± 0.95)x104 after 50 days. A statistically significant decrease in the level of Bifidobacterium was found for all experimental groups compared with the control group (6.64 ± 0.29)x106, but without significant differences among themselves (high-fat group (3.64 ± 0.27)x104, high-fiber group (2.84 ±

mice with a high-fat diet - (8.30 ± 1.16)x10b, ± 0.34)x104).

Fig. 7. Colonies of Yeast on the Sabouraud medium

Note: A - six-fold dilutions, an enlarged photo of the colony of Yeast, B - Yeast cells isolated from colonies, Gram-stained (sample obtained from inoculation of faeces of mice from group high-fiber on the 50st day of the experiment)

Table 1

The content of living microorganisms in 1 g of faeces, CFU*g--

Group Day of the experiment

0 17 31 50

Yeasts (Sabouraud Medium)

control (7.25 ± 0.76)x107 (6.63 ± 0.04)x107 (6.61 ± 0.47)x107 (7.78 ± 0.83)x107

high-fat (9.94 ± 1.70)x107 (6.92 ± 0.36)x107 (9.02 ± 0.71)x107 (7.28 ± 0.64) x108

high-fiber (9.25 ± 0.82)x107 (5.31 ± 1.63)x107 (7.21 ± 0.55) x106 (4.45 ± 0.84) x106

End of table 1

Group Day of the experiment

0 17 31 50

Enterobacteria (Endo Agar)

control (7.58 ± 0.71)x104 (7.83 ± 0.89)x104 (5.86 ± 0.90)x104 (6.25 ± 0.58)x104

high-fat (8.71 ± 0.96)x104 (6.83 ± 0.75)x104 (8.80 ± 0.85) x105 (8.30 ± 1.16)x106

high-fiber (5.51 ± 1.61)x104 (5.94 ± 0.61) x103 (8.38 ± 1.36)x102 (10.8 ± 1.91)x102

Lactobacilli (MPC Medium)

control (4.42 ± 0.82)x107 (5.81 ± 0.78)x107 (5.52 ± 0.86)x107 (4.72 ± 0.98)x107

high-fat (5.78 ± 0.62)x107 (7.51 ± 1.05)x107 (6.84 ± 0.87) x106 (4.44 ± 0.83) x105

high-fiber (6.06 ± 0.46)x107 (2.22 ± 0.95) x106 (5.12 ± 1.37)x105 (5.45 ± 0.95) x104

Bifidobacteria (Blaurock Medium)

control (7.73 ± 0.66)x106 (6.38 ± 0.41)x106 (6.58 ± 0.45)x106 (6.64 ± 0.29)x106

high-fat (5.98 ± 0.54)x106 (7.31 ± 0.91)x106 (4.75 ± 1.40)x105 (3.64 ± 0.27) x104

high-fiber (5.93 ± 1.87)x106 (5.70 ± 0.81) x105 (4.46 ± 0.75) x105 (2.84 ± 0.34) x104

Discussion

The notion that the microbiota and its influence is limited only to the host's digestive tract has long given way to a broader view of the association of the microbiota with host development, growth, and host physiology (Sommer & Backhed, 2013). Changing the diet or taking antibiotics leads to rapid changes in the microbiota, thereby affecting the state of the host-mi-crobiota relationship (David et al., 2014; Dethlefsen et al., 2008; Walker et al., 2011).

Food consumed by a person, passing through the digestive tract, is broken down into smaller components and provides intestinal bacteria with available nutrients and substrates. In turn, bacteria break down food components, provide the body with the necessary nutrients, stimulate the development of humoral and cellular immune responses, modulate metabolism, and synthesize several metabolites. Among them, the most studied are short-chain fatty acids, gases, vitamins (K2, B12, folic acid, riboflavin, thiamine) and secondary bile acids (Rowland et al., 2018). Interspecific competition of bacteria for life-supporting resources determines the composition of the community (Patnode et al., 2019). It has previously been shown that the microbial composition and function of the gut is highly dependent on diet and is sensitive to specific changes in the host's diet. However, it is very difficult to determine the role of microorganisms in the metabolism of individual nutrients, so the analysis of these relationships in individual diets is in many cases not clear. To

date, the greatest interest is the study of the impact on the intestinal microbiota of individual nutritional components, in particular fats, proteins, carbohydrates, as part of various diets, the most famous of which are the Western and Mediterranean diets. For example, in most studies, the term «high-fat diet» (HFD, High-Fat Diet) or the so-called «Western diet» refers to a diet high in fat (usually saturated fatty acids) and simple carbohydrates low in fiber, vitamins, minerals. This diet is often used to induce obesity in experimental animal studies (Malesza et al., 2021). However, the exact ratio of nutrients in this diet has not been determined and varies greatly between experiments, and as a result leads to inconsistent results. In most animal studies, the western diet increases the proportion of gram-negative species in the gut microbiota (including enterobacteria), which is also confirmed by our study (Cani et al., 2007; Kazura et al., 2023; de La Serreet et al., 2010; Kim et al., 2012). The number of Enterobacte-riaceae bacteria (mainly E. coli) in the intestinal contents of mice in the high-fat group began to increase after a month (on the 31st day of the experiment), and by the end of the experiment (50 days) it increased by 2 orders of magnitude. Such a shift towards an increase in gram-negative microorganisms in the intestine leads to increased absorption of bacterial lipopolysaccha-rides in the intestine and the development of «metabolic endotoxemia», and subsequently to obesity. Metabolic endotoxemia is also promoted by increased intestinal permeability and

bacterial translocation associated with a low degree of intestinal inflammation (Festi et al., 2014).

Also in our study, with a high-fat diet, the amount of yeast and yeast-like fungi in the faeces of mice increased only by the end of the experiment, on day 50. On the one hand, yeasts, predominantly of the Saccharomyces genus, play a positive role in health; they are producers of B vitamins, proteins, certain amino acids, trace elements (Foligné et al., 2010), and antioxidants (Badr et al., 2021). Some yeast strains, such as Saccharomyces cerevisiae and Saccharomyces cerevisiae var. boulardii are used as probiotic cultures for disease prevention (Lazo-Vélez et al., 2018; Badr et al., 2021 ; Abid et al., 2022), including for the treatment of diarrhea associated with irritable bowel syndrome (Leventogiannis et al., 2019) antibiotic-associated (Ehrhardt et al., 2016), Crohn's disease (Guslandi et al., 2000). Known enzymatic activity of yeast Saccharomyces against other microorganisms, namely the production of phosphatase against E. coli cells and protein phosphatase, inhibiting toxic surface endotoxins (Buts et al., 2006). Thus, with a diet low in protein and fiber, but with the addition of yeast Saccha-romyces cerevisiae to the diet, the concentration of E. coli was significantly reduced (Bastos et al., 2023). The increase in yeast cells may be a response to the increase in en-terobacteria, an attempt to normalize the environment and control the E. coli population.

On the other hand, even the common yeast Saccharomyces cerevisiae causes fungemia in people with weakened immune systems (Niault et al., 1999; Chertow et al., 1991), and there are also cases of disease in healthy people who used Saccharomyces cerevisiae as a probiotic (Smith et al., 2002; Debelian et al., 1997; Herbrecht & Nivoix, 2005). Isolated yeast strains from these patients have pathogenic potential and certain phenotypic characteristics, such as growth at 42°C, some hydrolytic activity, pseudohyphal and invasive growth, switching, and adhesion, which are associated with pathogen virulence (Ghannoum, 2000; Burik & Magee, 2001; Roman et al., 2007; Llanos et al., 2006).

In addition to the yeast Saccharomyces, the gut microbiota includes Pichia (P. pastoris), which are considered saprophytes and are used to some extent in public health (Weinacker et al., 2014). Opportunistic yeast-like fungi that live in the intestines include Candida (a prominent representative of C. albicans). Normally, Candida overgrowth is suppressed by the gut microbiota through colonization resistance (Fan et al., 2015). But immunosuppressed, increased permeability of the gut mucosal barrier by microbiota, due to malnutrition or broad-spectrum antibiotics, may contribute to the pathogenesis of C. albicans (Wang et al., 2023; d'Enfert et al., 2021). Probiotic bacterial cultures, such as Lactobacillus (Allonsius et al., 2019; Charlet et al., 2020) and Bifidobacterium (Ricci et al., 2022) can enter the fight against this fungus, which are able to inhibit the growth of many fungal cells by affecting their cell wall. In addition, they produce butyrate, which promotes intestinal barrier integrity and prevents bacterial translocation (Wong et al., 2006).

It has long been shown that a lipid-rich diet is associated with a significant reduction in Lactobacillus and Bifidobacterium (Wall et al., 2009; Cani et al., 2008). At the same time, in mice, a decrease in dietary fiber has a direct effect on microbiota diversity, namely its decrease, and leads to poor production of short-chain fatty acids (SCFAs) generated by the gut microbiota (Fig. 8), which reduce inflammation through various mechanisms (Kashyap et al., 2013; Trompette et al., 2014). In our study, we also observed a decrease in Bifidobacterium, by two orders of magnitude, while the number of Lactobacillus decreased by only 1 order. Bacteria of the genus Lactobacillus, in contrast to Bifidobacterium, show a higher ability to adapt to environmental changes, in addition, their numbers are usually higher.

In addition, animal data demonstrate that a Western-style diet promotes weight gain and increases visceral adiposity in animals. However, in our study, there was only 16% weight gain in high-fat group mice from the starting point of the experiment. This may be explained by dietary modification without the additional carbohydrate load in the diet, as is typical of Western style eating.

Fig. 8. The role of short-chain fatty acids generated by the gut microbiota Note: ATP - adenosine triphosphate, SCFA - short-chain fatty acid

On the other hand, a diet rich in dietary fiber have been shown to increase Lactobacillus and Bifdobacterium in many experiments (Makki et al., 2018). It should be noted that the term «dietary fiber» refers to two types of carbohydrates, fermentable carbohydrates that microorganisms use as a substrate, and non-fermentable (insoluble) carbohydrates that act as a filler (Chawla & Patil, 2010). Soluble fiber not only performs certain important physiological functions, but also contributes to the formation of important microflora, acting as a substrate for beneficial microorganisms, therefore, acts as a prebiotic and improves the health of the host. Insoluble fiber is practically not used as a substrate by microorganisms but serves as a kind of protection against the growth of unwanted microflora. It has the effect of accelerating the transit of food through the gastrointestinal tract, which did not depend on the presence of the microbial community in the intestine but excludes food decay and the development of pathogens.

Carefully controlled experiments in mice have shown that the amount and type of carbohydrates fed to the microbiota alter simple and complex microbial communities (Faith et al., 2011; Kashyap et al., 2013; Sonnenburg et al., 2010; Turnbaugh et al, 2009). Our study used a diet with only an increase in non-fermentable fiber, without the addition of protein, lipids, and microbial accessible fiber, and showed a significant reduction in the probiotic microorganisms Lactobacillus and Bifdobacterium along with Enterobacteriaceae and yeast. These results clearly show that the lack of available substrates in food leads to a decrease in the number of microorganisms in the intestine, and as a result, a decrease in metabolites. SCFAs, acetate, propionate, and butyrate are common end products of carbohydrate fermenting microbes in the distal intestine (Wong et al., 2006), and several factors, including dietary substrates, can influence the relative ratios and concentration (Macfarlane & Macfarlane, 2003; Topping &

Clifton, 2001). SCFAs are taken up by the host and serve as reserve calories from otherwise unavailable carbohydrates, but they also play various regulatory roles, including regulation of histone acetylation and signaling through G protein-coupled receptors (Brown et al., 2003; Davie, 2003). SCFAs generated by the microbiota are associated with anti-inflammatory effects, namely an increase in the number of regulatory T cells in the intestine (Furusawa et al., 2013). The effects of reduced SCFAs production on a diet low in fermentable carbohydrates may be exacerbated by changes in microbiota localization and disruption of the distal intestinal barrier (Wong et al., 2006) SCFAs also regulate energy homeostasis (Layden et al., 2013). Butyrate has a broad effect on the metabolism and circulating signals of propionate through the afferent nervous system, affecting glucone-ogenesis in the intestine, and leads to improved metabolic profiles and reduced weight gain (De Vadder et al, 2014; Lin et al., 2012). We did not observe significant weight gain in the highfiber mice, but we noted some passivity in the home cage, and the anxiety level was lower compared to the control group. Perhaps this is due precisely to the lack of SCFAs produced mainly by the probiotic bacteria Lactobacillus, Bifdobacterium and Enterobacteriaceae, and metabolic disorders in general.

A high fiber diet has long been associated with a «healthy» diet and a «healthy» microbiota, such as increased microbial diversity (McBurney et al, 2019), but results can be conflicting in some cases (So et al, 2018). Thus, several studies have demonstrated the growth of probiotic microorganism (Lactobacillus, Bifdobacterium) in response to a high intake of dietary fiber, which included fructans and galac-tooligosaccharides related to fermentable carbohydrates (So et al, 2018). Resistant starch consumption increased Bifidobacterium, Fae-

calibacterium, Eubacterium, Enterobacteriaceae (E. coli), while at the same time decreased some strains of Ruminococcus (Martinez et al, 2010; Alfa et al, 2018). Insoluble non-fermentable fiber such as cellulose can be broken down by cellulose-metabolizing microbes such as Ruminococcus and Fibrobacter (Flint et al, 2008). Thus, the gut microbiota is highly dependent on dietary fiber as a source of energy. Applying the correct ratio of insoluble to soluble fiber can determine the ratio of microbial composition in the gut, the production of SCFAs and other substances.

Conclusion

Obviously, diet is one of the main factors that shapes the appearance and determines the direction of the functioning of the intestinal microbiota. The abundance of certain nutrients leads to the overgrowth of certain types of bacteria, thereby crowding out others. Previously, many studies have shown that both long-term and short-term dietary interventions cause significant changes in the gut microbial ecosystem. However, the exact mechanisms by which certain dietary components exert their influence on the composition of the gut microbiota remain uncertain. Moreover, despite the non-exponential growth of research in this area, dietary impact studies suffer from a lack of specificity, and therefore experimental data vary and cannot be used for medical and therapeutic purposes. The multicomponent nature of the diets used in the experiments, with the partial dominance of a single nutrient, does not allow establishing a clear correlation between changes in the microbiota and the source that causes them. Nevertheless, the results obtained demonstrate the possibility of using dietary manipulation as a therapeutic method for correcting metabolic activity and the concentration of opportunistic microorganisms in the intestine.

References

ABID R., WASEEM H., ALI J., GHAZANFAR S., MUHAMMAD ALI G., ELASBALI A.M. & ALHARE-THI S.H. (2022): Probiotic Yeast Saccharomyces: Back to Nature to Improve Human Health. Journal of fungi (Basel) 8(5), 444.

ABU-SINI M.K., MAHARMAH RA., ABULEBDAH D.H. & AL-SABI M.N.S. (2023): Isolation and Identification of Coliform Bacteria and Multidrug-Resistant Escherichia coli from Water Intended for Drug Compounding in Community Pharmacies in Jordan. Healthcare (Basel) 11(3), 299.

AFINEEV SKAYA A.Y., MAL'KOV O.A. & GOVORUKHINA A.A. (2020): The Role of Intestinal Microbiota in the Pathogenesis of Atherosclerosis and Promising Preventive Measures (Review). Journal of Medical and Biological Research 8(2), 184-193.

ALFA M.J., STRANG D., TAPPIA P.S., GRAHAM M., VAN DOMSELAAR G., FORBES J.D., LAMINMAN V., OLSON N., DEGAGNE P., BRAY D., MURRAY B.L., DUFAULT B. & LIX L.M. (2018): A randomized trial to determine the impact of a digestion resistant starch composition on the gut microbiome in older and mid-age adults. Clinical nutrition 37(3), 797-807.

ALLONSIUS C.N., VANDENHEUVEL D., OERLEMANS E.F.M., PETROVA M.I., DONDERS G.G.G., COS P., DELPUTTE P. & LEBEER S. (2019): Inhibition of Candida albicans morphogenesis by chi-tinase from Lactobacillus rhamnosus GG. Scientific reports 9(1), 2900.

BADR H., EL-BAZ A., MOHAMED I., SHETAIA Y, EL-SAYED A S A. & SOROUR N. (2021): Biopro-cess optimization of glutathione production by Saccharomyces boulardii: biochemical characterization of glutathione peroxidase. Archives of microbiology 203(10), 6183-6196.

BASTOS TS., SOUZA C.M.M., LEGENDRE H., RICHARD N., PILLA R., SUCHODOLSKI J.S., DE OLIVEIRA S.G., LESAUX A.A. & FÉLIX A.P. (2023): Effect of Yeast Saccharomyces cerevisiae as a Probiotic on Diet Digestibility, Fermentative Metabolites, and Composition and Functional Potential of the Fecal Microbiota of Dogs Submitted to an Abrupt Dietary Change. Microorganisms 11(2): 506.

BROWN A.J., GOLDSWORTHY S.M., BARNES A.A., EILERT M M., TCHEANG L., DANIELS D., MUIR A.I., WIGGLESWORTH M.J., KINGHORN I., FRASER N.J., PIKE N.B, STRUM J.C., STEPLEWSKI K.M., MURDOCK PR., HOLDER J.C., MARSHALL F.H., SZEKERES P.G., WILSON S., IGNAR D.M., FOORD S.M., WISE A. & DOWELL S.J. (2003): The Orphan G protein-coupled receptors GPR41 and GPR43 are activated by propionate and other short chain carboxylic acids. The Journal of biological chemistry 278(13), 11312-11319.

BUTS J.P., DEKEYSER N., STILMANT C., DELEM E., SMETS F. & SOKAL E. (2006): Saccharomyces boulardii produces in rat small intestine a novel protein phosphatase that inhibits Escherichia coli endotoxin by dephosphorylation. Pediatric research 60(1), 24-29.

CANI P.D., AMAR J., IGLESIAS M A., POGGI M., KNAUF C., BASTELICA D., NEYRINCK A.M., FAVA F., TUOHY K.M., CHABO C., WAGET A., DELMÉ E., COUSIN B., SULPICE T., CHAMON-TIN B., FERRIÈRES J., TANTI J.F., GIBSON GR., CASTEILLA L., DELZENNE N. M., ALESSI M.C. & BURCELIN R. (2007): Metabolic endotoxemia initiates obesity and insulin resistance. Diabetes 56(7), 1761-1772.

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CANI P.D., BIBILONI R., KNAUF C., WAGET A., NEYRINCK A.M., DELZENNE N.M. & BURCELIN R. (2008): Changes in gut microbiota control metabolic endotoxemia-induced inflammation in high-fat diet-induced obesity and diabetes in mice. Diabetes 57(6), 1470-1481.

CHARLET R., BORTOLUS C., SENDID B. & JAWHARA S. (2020): Bacteroides thetaiotaomicron and Lactobacillus johnsonii modulate intestinal inflammation and eliminate fungi via enzymatic hydrolysis of the fungal cell wall. Scientific reports 10(1), 11510.

CHAWLA R. & PATIL G.R. (2010): Soluble dietary fiber. Comprehensive Reviews in Food Science and Food Safety 9(2), 178-196.

CHERTOW G M. MARCANTONIO E R. & WELLS R.G. (1991): Saccharomyces cerevisiae empyema in a patient with esophago-pleural fistula complicating variceal sclerotherapy. Chest 99(6), 1518-1519.

CROCI S., D'APOLITO L.I., GASPERI V., CATANI M.V. & SAVINI I. (2021): Dietary Strategies for Management of Metabolic Syndrome: Role of Gut Microbiota Metabolites. Nutrients 13(5), 1389.

DAVID L.A., MAURICE C F., CARMODY R.N., GOOTENBERG D.B., BUTTON J.E., WOLFE B E., LING A.V., DEVLIN A S., VARMA Y., FISCHBACH M A., BIDDINGER S.B, DUTTON R.J. & TURNBAUGH P.J. (2014): Diet rapidly and reproducibly alters the human gut microbiome. Nature 505(7484), 559-563.

DAVIE J.R. (2003): Inhibition of histone deacetylase activity by butyrate. The Journal of nutrition 133(7 Suppl), 2485S-2493S.

DEBELIAN G.J., OLSEN I. & TRONSTAD L. (1997): Observation of Saccharomyces cerevisiae in blood of patient undergoing root canal treatment. International endodontic journal 30(5), 313-317.

DE LA SERRE C.B., ELLIS C.L., LEE J., HARTMAN A.L., RUTLEDGE J.C. & RAYBOULD H E. (2010): Propensity to high-fat diet-induced obesity in rats is associated with changes in the gut microbiota and gut inflammation. American journal ofphysiology. Gastrointestinal and liver physiology 299(2), G440-G448.

DE LLANOS R., FERNÁNDEZ-ESPINAR M.T. & QUEROL A. (2006): A comparison of clinical and food Saccharomyces cerevisiae isolates on the basis of potential virulence factors. Antonie Van Leeuwenhoek 90(3), 221-231.

D'ENFERT C., KAUNE A.K., ALABAN LR., CHAKRABORTY S., COLE N., DELAVY M., KOSMALA

D., MARSAUX B., FRÓIS-MARTINS R, MORELLI M., ROSATI D., VALENTINE M., XIE Z., EMRITLOLL Y., WARN P.A., BEQUET F., BOUGNOUX M.E., BORNES S., GRESNIGT M.S., HUBE B., JACOBSEN I.D., LEGRAND M., LEIBUNDGUT-LANDMANN S., MANICHANH C., MUNRO C A., NETEA M.G., QUEIROZ K., ROGET K., THOMAS V., THORAL C., VAN DEN ABBEELE P., WALKER A.W. & BROWN A.J.P. (2021): The impact of the Fungus-Host-Microbiota interplay upon Candida albicans infections: current knowledge and new perspectives. FEMS microbiology reviews 45(3), fuaa060.

DETHLEFSEN L., HUSE S. SOGIN M L. & RELMAN D A. (2008): The pervasive effects of an antibiotic on the human gut microbiota, as revealed by deep 16S rRNA sequencing. PLoS biology 6(11), e280.

DE VADDER F., KOVATCHEVA-DATCHARY P., GONCALVES D. VINERA J., ZITOUN C., DU-CHAMPT A., BÄCKHED F. & MITHIEUX G. (2014): Microbiota-generated metabolites promote metabolic benefits via gut-brain neural circuits. Cell 156(1-2), 84-96.

DI PAOLA M., RIZZETTO L., STEFANINI I., VITALI F., MASSI-BENEDETTI C., TOCCI N., ROMANI L., RAMAZZOTTI M., LIONETTI P., DE FILIPPO C. & CAVALIERI D. (2020): Comparative immuno-phenotyping of Saccharomyces cerevisiae and Candida spp. strains from Crohn's disease patients and their interactions with the gut microbiome. Journal of translational autoimmunity 3, 100036.

EHRHARDT S., GUO N., HINZ R., SCHOPPEN S., MAY J., REISER M., SCHROEDER M P., SCHMIEDEL S., KEUCHEL M., REISINGER E C., LANGEHEINECKE A., DE WEERTH A., SCHUCHMANN M., SCHABERG T., LIGGES S., EVESLAGE M, HAGEN R.M., BURCHARD G.D. & LOHSE A.W. (2016): Saccharomyces boulardii to Prevent Antibiotic-Associated Diarrhea: A Randomized, Double-Masked, Placebo-Controlled Trial. Open forum infectious diseases 3(1), ofW011.

FAITH J.J., MCNULTY N.P., REY F E. & GORDON J.I. (2011): Predicting a human gut microbiota's response to diet in gnotobiotic mice. Science 333(6038), 101-104.

FAN D., COUGHLIN LA., NEUBAUER MM., KIM J., KIM M.S., ZHAN X., SIMMS-WALDRIP T.R., XIE Y., HOOPER L.V. & KOH A Y. (2015): Activation of HIF-1a and LL-37 by commensal bacteria inhibits Candida albicans colonization. Nature medicine 21(7), 808-814.

FARAHMAND N., OUOBA L.I.I., NAGHIZADEH RAEISI S., SUTHERLAND J. & GHODDUSI H.B. (2021): Probiotic Lactobacilli in Fermented Dairy Products: Selective Detection, Enumeration and Identification Scheme. Microorganisms, 9(8), 1600.

FESTI D., SCHIUMERINI R., EUSEBI L.H., MARASCO G., TADDIA M. & COLECCHIA A. (2014): Gut microbiota and metabolic syndrome. World journal of gastroenterology 20(43), 16079-16094.

FLINT H.J., BAYER E.A., RINCON M.T., LAMED R. & WHITE B.A. (2008): Polysaccharide utilization by gut bacteria: potential for new insights from genomic analysis. Nature reviews. Microbiology 6(2), 121-131.

FOLIGNÉ B., DEWULF J., VANDEKERCKOVE P., PIGNÉDE G. & POT B. (2010): Probiotic yeasts: antiinflammatory potential of various non-pathogenic strains in experimental colitis in mice. World journal of gastroenterology 16(17), 2134-2145.

FOSTER J.A. (2013): Gut feelings: bacteria and the brain. Cerebrum: the Dana forum on brain science 2013, 9.

FOSTER J A., LYTE M., MEYER E. & CRYAN J.F. (2016): Gut Microbiota and Brain Function: An Evolving Field in Neuroscience. The international journal of neuropsychopharmacology 19(5), 35-42.

FURUSAWA Y., OBATA Y., FUKUDA S., ENDO T A. NAKATO G., TAKAHASHI D. NAKANISHI Y., UETAKE C., KATO K., KATO T., TAKAHASHI M., FUKUDA N.N., MURAKAMI S., MIYAUCHI

E., HINO S., ATARASHI K., ONAWA S., FUJIMURA Y., LOCKETT T., CLARKE J.M., TOPPING D.L., TOMITA M., HORI S., OHARA O., MORITA T., KOSEKI H., KIKUCHI J., HONDA K., HASE K. & OHNO H. (2013): Commensal microbe-derived butyrate induces the differentiation of colonic regulatory T cells. Nature 504(7480), 446-450.

GHANNOUM M.A. (2000): Potential role of phospholipases in virulence and fungal pathogenesis. Clinical microbiology reviews 13(1), 122-143.

GUSLANDI M., MEZZI G., SORGHI M. & TESTONI P.A. (2000): Saccharomyces boulardii in maintenance treatment of Crohn's disease. Digestive diseases and sciences 45(7), 1462-1464.

HERBRECHT R. à NIVOIX Y. (2005): Saccharomyces cerevisiae fungemia: an adverse effect of Saccharomyces boulardii probiotic administration.Clinical infectious diseases: an official publication of the Infectious Diseases Society of America 40(11), 1б35-1б37.

KASHYAP P.C., MARCOBAL A. URSELL L.K., SMITS S.A. SONNENBURG ED., COSTELLO E.K., HIGGINBOTTOM S.K., DOMINO S.E., HOLMES SP., RELMAN D.A., KNIGHT R., GORDON J.I. à SONNENBURG J.L. (2013): Genetically dictated change in host mucus carbohydrate landscape exerts a diet-dependent effect on the gut microbiota. Proceedings of the National Academy of Sciences of the United States of America 110(42), 17059-170б4.

KASHYAP P.C., MARCOBAL A., URSELL L.K., LARAUCHE M., DUBOC H., EARLE K.A., SONNENBURG ED., FERREYRA JA., HIGGINBOTTOM S.K., MILLION M., TACHE Y., PASRICHA P.J., KNIGHT R., FARRUGIA G. à SONNENBURG J.L. (2013): Complex interactions among diet, gastrointestinal transit, and gut microbiota in humanized mice. Gastroenterology 144(5), 9б7-77.

KAZURA W., MICHALCZYK K. à STYGAR D. (2023): The Relationship between the Source of Dietary Animal Fats and Proteins and the Gut Microbiota Condition and Obesity in Humans. Nutrients 15(14), 3082.

KIM K.A., GU W., LEE I.A., JOH E.H. à KIM D.H. (2012): High fat diet-induced gut microbiota exacerbates inflammation and obesity in mice via the TLR4 signaling pathway. PloS one 7(10), e47713.

KHABIROV A., AVZALOV R., TSAPALOVA G., ANDREEVA A. à BASHAROV A. (2022): Effect of a probiotic containing Lactobacilli and Bifidobacteria on the metabolic processes, litter microbiocenosis, and production indicators of broiler Pekin ducklings. Vet World 15(4): 998-1005.

KOCHKINA S.O., GORDEEV S.S. à MAMEDLI Z.Z. (2019): Role of human microbiota in the development of colorectal cancer. Pelvic Surgery and Oncology 9(3), 11-7.

LAYDEN B T., ANGUEIRA A.R. BRODSKY M., DURAI V. à LOWE W.L. J.R. (2013): Short chain fatty acids and their receptors: new metabolic targets. Translational research: the journal of laboratory and clinical medicine 161(3), 131-140.

LAZO-VÉLEZ M.A., SERNA-SALDÍVAR S.O., ROSALES-MEDINA MF., TINOCO-ALVEAR M. à BRIONES-GARCÍA M. (2018): Application of Saccharomyces cerevisiae var. boulardii in food processing: a review. Journal of applied microbiology 125(4), 943-951.

LEVENTOGIANNIS K., GKOLFAKIS P., SPITHAKIS G., TSATALI A., PISTIKI A., SIOULAS A., GIAMARELLOS-BOURBOULIS E.J. à TRIANTAFYLLOU K. (2019): Effect of a Preparation of Four Probiotics on Symptoms of Patients with Irritable Bowel Syndrome: Association with Intestinal Bacterial Overgrowth. Probiotics and antimicrobial proteins 11(2), б27-б34.

LIN H.V., FRASSETTO A., KOWALIK EJ. JR., NAWROCKI A.R., LU MM., KOSINSKI J.R., HUBERT J A, SZETO D., YAO X., FORREST G. à MARSH D.J. (2012): Butyrate and propionate protect against diet-induced obesity and regulate gut hormones via free fatty acid receptor 3-independent mechanisms. PLoS one 7(4), e35240.

MACFARLANE S. à MACFARLANE G.T. (2003): Regulation of short-chain fatty acid production. The Proceedings of the Nutrition Society 62(1), б7-72.

MAKKI, K., DEEHAN, E. C., WALTER, J. & BÄCKHED, F. (2018): The Impact of Dietary Fiber on Gut Microbiota in Host Health and Disease. Cell host & microbe 23(б), 705-715.

MALESZA I. J., MALESZA M., WALKOWIAK J., MUSSIN N., WALKOWIAK, D., ARINGAZINA R., BARTKOWIAK-WIECZOREK J. & MADRY E. (2021): High-Fat, Western-Style Diet, Systemic Inflammation, and Gut Microbiota: A Narrative Review. Cells 10(11), 31б4.

MALLICK H., MA S., FRANZOSA E.A., VATANEN T, MORGAN X.C. à HUTTENHOWER C. (2017): Experimental design and quantitative analysis of microbial community multiomics. Genome biology 18(1), 228.

MARTÍNEZ I., KIM J., DUFFY PR., SCHLEGEL V.L. & WALTER J. (2010): Resistant starches types 2 and 4 have differential effects on the composition of the fecal microbiota in human subjects. PLoS One 5(11), e15046.

MC BURNEY M.I., DAVIS C., FRASER CM., SCHNEEMAN B.O., HUTTENHOWER C., VERBEKE K., WALTER J. à LATULIPPE M.E. (2019): Establishing What Constitutes a Healthy Human Gut Microbiome: State of the Science, Regulatory Considerations, and Future Directions. The Journal of nutrition 149(11), 1882-1895.

MEIJNIKMAN AS., GERDES V.E., NIEUWDORP M. à HERREMA H. (2018): Evaluating Causality of Gut Microbiota in Obesity and Diabetes in Humans. Endocrine reviews 39(2), 133-153.

NIAULT M., THOMAS F., PROST J., ANSARI F.H. & KALFON P. (1999): Fungemia due to Saccharomyces species in a patient treated with enteral Saccharomyces boulardii. Clinical infectious diseases: an official publication of the Infectious Diseases Society of America 28(4), 930.

PATNODE ML., BELLER ZW., HAN N.D., CHENG J., PETERS S.L., TERRAPON N., HENRISSAT B., LE GALL S., SAULNIER L., HAYASHI D.K., MEYNIER A., VINOY S., GIANNONE R.J., HET-TICH R.L. & GORDON J.I. (2019): Interspecies Competition Impacts Targeted Manipulation of Human Gut Bacteria by Fiber-Derived Glycans. Cell 179(1), 59-73, e13.

RICCI L., MACKIE J., DONACHIE G.E., CHAPUIS A., MEZEROVÁ K., LENARDON M.D., BROWN A.J.P., DUNCAN S.H. & WALKER A.W. (2022): Human gut bifidobacteria inhibit the growth of the opportunistic fungal pathogen Candida albicans. FEMSMicrobiolEcol. 98(10), fiac095.

ROMÁN E., ARANA D.M., NOMBELA C., ALONSO-MONGE R. & PLA J. (2007): MAP kinase pathways as regulators of fungal virulence. Trends Microbiol 15(4), 181-90.

ROMANCHUK P.I. (2020): Age and microbiota: epigenetic and dietary protection, endothelial and vascular rehabilitation, the new operated healthy biomicrobiota. Bulletin of Science and Practice 6(2), 67-110.

ROWLAND I., GIBSON G., HEINKEN A., SCOTT K., SWANN J., THIELE I. & TUOHY K. (2018): Gut microbiota functions: metabolism of nutrients and other food components. European journal of nutrition 57(1), 1-24.

SMITH D., METZGAR D., WILLS C. & FIERER J. (2002): Fatal Saccharomyces cerevisiae aortic graft infection. Journal of clinical microbiology 40(7), 2691-2692.

SO D., WHELAN K., ROSSI M., MORRISON M., HOLTMANN G., KELLY J.T., SHANAHAN E.R, STAUDACHER H.M. & CAMPBELL K.L. (2018): Dietary fiber intervention on gut microbiota composition in healthy adults: a systematic review and meta-analysis. The American journal of clinical nutrition 107(6), 965-983.

SOMMER F. & BÄCKHED F. (2013): The gut microbiota - masters of host development and physiology. Nature reviews. Microbiology 11(4), 227-238.

SONNENBURG ED., ZHENG H., JOGLEKAR P., HIGGINBOTTOM S.K., FIRBANK S.J., BOLAM D.N. & SONNENBURG J.L. (2010): Specificity of polysaccharide use in intestinal bacteroides species determines diet-induced microbiota alterations. Cell 141(7), 1241-1252.

SUDO N. (2016): Effects of Gut Microbiota on Stress Response and Behavioral Phenotype of the Host. Brain Nerve 68(6), 595-605.

SUN P., SU L., ZHU H., LI X., GUO Y., DU X., ZHANG L. & QIN C. (2021): Gut Microbiota Regulation and Their Implication in the Development of Neurodegenerative Disease. Microorganisms 9(11), 2281.

TOPPING D.L. & CLIFTON P.M. (2001): Short-chain fatty acids and human colonic function: roles of resistant starch and nonstarch polysaccharides. Physiological reviews 81(3), 1031-1064.

TROMPETTE A., GOLLWITZER ES., YADAVA K., SICHELSTIEL A.K., SPRENGER N., NGOM-BRU C., BLANCHARD C., JUNT T., NICOD L P., HARRIS N.L. & MARSLAND B.J. (2014): Gut microbiota metabolism of dietary fiber influences allergic airway disease and hematopoiesis. Nat Med 20(2), 159-166.

TURNBAUGH P.J., RIDAURA V.K., FAITH J.J., REY FE., KNIGHT R. & GORDON J.I. (2009): The effect of diet on the human gut microbiome: a metagenomic analysis in humanized gnotobiotic mice.

Science translational medicine 1(6), 6ra14.

VAN BURIK J.A. & MAGEE P.T. (2001): Aspects of fungal pathogenesis in humans. Annual review of microbiology 55, 743-772.

WALL R., ROSS R.P., SHANAHAN F., O'MAHONY L., O'MAHONY C., COAKLEY M., HART O., LAWLOR P., QUIGLEY E M., KIELY B., FITZGERALD G.F. & STANTON C. (2009): Metabolic activity of the enteric microbiota influences the fatty acid composition of murine and porcine liver and adipose tissues. The American journal of clinical nutrition 89(5), 1393-1401.

WALKER A.W., INCE J., DUNCAN S.H. WEBSTER L.M. HOLTROP G., ZE X., BROWN D., STARES M.D., SCOTT P., BERGERAT A., LOUIS P., MCINTOSH F., JOHNSTONE A.M., LOBLEY G.E., PARKHILL J. & FLINT H.J. (2011): Dominant and diet-responsive groups of bacteria within the human colonic microbiota. The ISME journal 5(2), 220-230.

WANG F., WANG Z. & TANG J. (2023): The interactions of Candida albicans with gut bacteria: a new strategy to prevent and treat invasive intestinal candidiasis. Gut Pathog 15(1), 30.

WEINACKER D., RABERT C., ZEPEDA A.B., FIGUEROA CA., PESSOA A. & FARiAS J.G. (2014): Applications of recombinant Pichia pastoris in the healthcare industry. razilian journal of microbiology 44(4), 1043-1048.

WONG J.M., DE SOUZA R., KENDALL C.W., EMAM A. & JENKINS D.J. (2006): Colonic health: fermentation and short chain fatty acids. Journal of clinical gastroenterology 40(3), 235-243.

YUDINA YU.V., KORSUNSKY A.A., AMINOVA A.I., ABDULLAEVA G.D. & PRODEUS A.P. (2019): Gut microbiota as a separate body system. Russian Journal of Evidence-Based Gastroenterology 8(4), 36-43.

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