Over the past decade, the gut microbiome has been recognized as a key factor in the development and progression of obesity and related diseases, making it the subject of intense research7,8. Research indicates that individuals with diet-induced obesity have significant changes in their gut microbiome, including decreased bacterial diversity and an increased ability to extract energy from food, which may contribute to metabolic disorders.

AUTHORS:

Sara Kralj, MSc, Master in Nutrition & Ira Renko, MSc, Master in Molecular biotechnology

According to the International Classification of Diseases 11 (ICD-11), obesity is defined as a chronic and complex disease characterized by excessive fat accumulation that may harm health. In most cases, it is a multifactorial disease caused by an environment that promotes weight gain, psychosocial factors, and genetic variations.

In a subset of patients, specific primary causes can be identified (medications, diseases, immobility, medical procedures, monogenic diseases/genetic syndromes).

Additionally, obesity is associated with a range of health conditions and diseases, including cardiovascular diseases, type 2 diabetes (T2DM), obstructive sleep apnea, and osteoarthritis, emphasizing its sig- nificant impact on the development of various disorders, making it one of the leading causes of mortality worldwide1.

Body mass index (BMI) serves as a surrogate indicator of body fat and is calculated as the ratio of body weight (kg) to the square of height (m²). BMI categories for defining obesity vary depending on age and sex in infants, children, and adolescents2 According to the World Health Organization (WHO), overweight and obesity are defined as excessive or abnormal fat accumulation that may pose a risk to health. BMI is less reliable in individuals with well-developed lean mass, where a high BMI does not necessarily indicate increased fat mass, and should therefore be considered a rough guideline3,4.

Epidemiology and factors that lead to obesity

Since 1975, global obesity rates have nearly tripled, making it one of the most significant public health issues in today's society5,4. Previously, obesity was considered a problem mainly affecting high-income countries. However, overweight and obesity have become global concerns, including in middleand low-income countries, particularly in urban areas2,5

The WHO highlights the growing issue of obesity affecting an increasing number of children and spreading across all continents. WHO data from 2016 recorded more than 340 million children and adolescents aged 5 to 19 as overweight or obese. The prevalence of overweight and obesity in this age group has increased dramatically from 4% in 1975 to over 18% in 2016. The rise is similar among both boys and girls, with 18% of girls and 19% of boys classified as overweight in 20165

The etiology of obesity is complex. Obesity is influenced by factors that cannot be controlled, such as genetic, biological, or endocrine factors, as well as factors that can be influenced, such as environmental and social factors, along with other factors that may contribute to the development of obesity6,4 Over the past decade, the gut microbiome has been recognized as a key factor in the development and progression of obesity and related diseases, making it the subject of intense research7,8. The gut microbiota plays a crucial role in the maturation of innate immunity during early life, while simultaneously recognizing and modulating numerous environmental signals and influencing various physiological processes. It acts as an intermediary between the host and external factors, potentially impacting human health. Changes in the composition of beneficial bacteria can have significant consequences, including the promotion of certain aspects of disease development. The microbiota can be influenced by various factors, such as diet, diseases, medication use, and infections9

A healthy gut microbiome is characterized by high diversity and balance, which are essential for maintaining immune homeostasis and resistance to pathogens. Additionally, the microbiome establishes a synergistic relationship with the host, influencing nutrient absorption, energy regulation, and protection against pathogens10-12. However, disruptions in homeostasis, which may be caused by factors such as host genetics, diet, medications, infections, and circadian rhythm, can contribute to the development of various diseases, including obesity and accelerated aging13. In obese individuals, the microbiome exhibits an increased capacity to extract energy from food compared to individuals with a healthy body weight, potentially leading to higher energy intake, which precedes obesity and the development of metabolic disorders14

Significant changes in the composition of the gut microbiome in obese individuals include alterations in the presence, abundance, and activity of the Bacteroidales order (including species such as Lactobacillus spp., Bifidobacterium spp., Bacteroides spp., and Enterococcus spp.). The ratio of Firmicutes to Bacteroidetes shifts, along with a noted decrease in

Clostridia , including Clostridiumleptum , and Enterobacter spp.15-18. The composition of the gut microbiome also varies depending on the degree of obesity (Table 1). Specifically, significant reductions in bacterial genera such as Akkermansia, Faecalibacterium, Oscillibacter,and Alistipeshave been recorded in obese individuals compared to those with normal body weight14

Higher levels of Lactobacillus reuteri have been associated with obesity, potentially leading to significant weight gain, whereas species such as Bifidobacterium animalis, Methanobrevibacter smithii , and other Lactobacillus species are more abundant in individuals with normal body weight. In contrast, M. smithii levels are lower in obese individuals compared to those with normal weight19. These alterations in gut microbiome composition could serve as early diagnostic markers for treating type 2 diabetes (T2DM) in high-risk patients20. Additional studies have also shown that the gut microbiome can influence glucose metabolism, while certain microbial species, such as Bacteroides faecalis, may accelerate diabetes progression21,22

Dietary intervention

Diet has a significant impact on the composition of the gut microbiome and represents one of the most important factors influencing changes in bacterial flora24. Research shows that weight loss, induced by a diet with reduced carbohydrate or fat intake, can lead to increased bacterial diversity in the gut and a reduction in chronic systemic inflammation25. Certain dietary patterns are associated with characteristic microbiotic profiles. For instance, an increased presence of the genus Prevotella is linked to a fiber-rich diet, while a diet high in protein is associated with a predominance of the genus Bacteroides25. Additionally, specific dietary components, such as caffeine, omega-3 fatty acids, and green tea can promote the growth of beneficial gut bacteria and positively influence the Firmicutes-to-Bacteroidetes ratio26. Furthermore, the intake of fruits, vegetables, and extra virgin olive oil contributes to positive changes in microbiome composition27

The Mediterranean diet, rich in prebiotics, can also have a beneficial effect on gut microbiome stability24. A clinical study conducted by Zimmer et al. showed that individuals following a vegetarian or vegan diet have significantly lower levels of bacteria from the genera Bacteroides, Bifidobacterium , as well as Escherichia coli and Enterobacteriaceaespecies in their gut microbiota compared to omnivores. Since vegetarian and vegan diets typically contain higher amounts of carbohydrates and dietary fiber, the gut microbiome under these conditions ferments indigestible polysaccharides into short-chain fatty acids (SCFAs), which can have a positive impact on gut health28. Reduced gut microbiome diversity in individuals consuming a Western diet has been associated with an increased prevalence of obesity and related diseases, including coronary vascular disease, metabolic syndrome, and non-alcoholic fatty liver disease (NAFLD)29.

Besides dietary interventions, gut microbiome modulation can also be achieved through probiotics, such as Bifidobacterium and Lactobacillus species,

TABLE 1 Evidence for each ingredient on sperm parameters and/or live birth rates

Upregulated

Overweight pregnant women

Obese women: Bacteroides, Staphylococcus aureus, Enterobacteriaceae, Escherichia coli, Staphylococcus

Excessive weight gain: Escherichia coli, C. leptum, Staphylococcus

Mild weight gain: Clostridium Bifidobacterium

Overweight and obese

Pre-pregnancy and infant

Overweight/obese women in metabolic disorder group

Staphylococcus aureus, Firmicutes-to-Bacteroidetes ratio; Lactobacillus spp. (Lactobacillus reuteri, Lactobacillus), E. coli, Prevotellaceae, Archaea, Firmicutes

Infants whose mothers are overweight: Akkermansia muciniphila, Staphylococcus aureus, Clostridium histolyticum,

Infants of mothers with ex-cessive weight gains: Clostridium histolyticum, Staphylococcus aureus

E. rec-to-Bacto ratio, E. rectale-C coccoides, Gramnegative,Firmicutes/acteroidetesratio as well as prebiotics like lactulose, inulin, fructooligosaccharides, and galactooligosaccharides, which contribute to balancing the gut ecosystem30,31 Westernization of dietary habits leads to disruptions in gut microbiota composition32. Studies have shown that African children consuming a low-fat, high-fiber diet have greater microbial diversity in their gut and a lower number of pathogenic bacteria. These children also have higher levels of Bacteroidetes compared to European children, who have a higher abundance of Firmicutes and Enterobacteriaceae, such as Shigella and Escherichia33. Conversely, a diet high in fat and low in fiber reduces microbial diversity, decreases the number of protective bacteria, and lowers SCFA production. The consumption of fiber-rich foods, such as fruits, vegetables, and legumes, increases gut microbiota diversity and is also associated with lower weight gain in humans, independent of total energy intake34

Probiotics

One approach to combating obesity and related diseases involves modifying the microbiota of obese individuals to increase the diversity of beneficial microorganisms35. Studies have shown a link between probiotics and weight reduction in both animals and humans36. An inadequate diet in obese individuals can facilitate the extraction of energy from consumed food and promote its storage in the host's adipose tissue. Research suggests that probiotics and synbiotics may contribute to weight reduction through various mechanisms.

Probiotics promote the restoration of tight junctions between epithelial cells, reducing intestinal permeability, preventing bacterial translocation, and alleviating inflammation caused by lipopolysaccharides (LPS). The reduction in inflammation improves insulin sensitivity in the hypothalamus, enhancing

Downregulated

Excessive weight gain: Akkermansia muciniphila, Bifidobacterium

Bacteroidesvulgatus, M. smithii

Bacteroides-Prevotella the sensation of satiety.

Additionally, increased concentrations of leptin in adipose tissue, glucagon-like peptide 1 (GLP-1), and pancreatic polypeptide (PYY) in the gut contribute to reduced food intake by increasing satiety.

Several bacterial strains have demonstrated positive effects, including reducing endotoxemia, adiposity, tissue inflammation, body weight, leptin (LEP) levels, and overall energy intake. Among the most extensively studied probiotic species are Bifidobacterium and Lactobacillus spp., though their effects on obesity depend on the specific strain and species. The composition of the gut microbiota varies among individuals, but most studies indicate that the Firmicutes-to-Bacteroidetes ratio is significantly higher in obese individuals. Additionally, previous research has shown an increased presence of Bacteroidetes in stool following weight loss, while a higher abundance of Firmicutes has been linked to the development of obesity. Furthermore, studies have demonstrated that overweight and obese individuals with a high Firmicutes/Bacteroides ratio achieve better health outcomes when following a diet rich in fiber and whole grains compared to those with a lower ratio of these bacterial species37

One study examined the use of probiotic species Lactobacillus and Bifidobacterium in obese animals due to their low pathogenicity and high resistance to antibiotic activity38 Bifidobacterium contributed to reducing inflammation, improving insulin sensitivity, and lowering serum cholesterol and triglyceride levels, primarily by decreasing intestinal permeability. Additionally, the application of probiotics containing Lactobacillus in obese animals resulted in effective reductions in body fat mass and improved regulation of blood lipids and glucose, which was attributed to increased fatty acid oxidation and inhibition of lipoprotein lipase activity39. The use of certain Lactobacillus strains has also been investigated in humans.

A study by Luoto et al. included two groups of children. One group received a placebo, while the other consumed the L. rhamnosus probiotic, which contributed to the regulation of the child's body weight during the first few years of life and during the initial stages of excessive weight gain, though this effect was not observed in later stages of life40,41. Over twelve weeks of application in obese individuals, the Lactobacillus gasseri SBT2055 probiotic contributed to the reduction of abdominal obesity and body weight, while no such effect was seen in the group receiving L. gasseri BNR1742,43. Moreover, in obese children with insulin resistance, the intake of Aspergillus flavus CECT7765 resulted in a significant reduction in body weight44. In adults, Lactobacillus and Bifidobacterium contributed to significant reductions in body weight, BMI, waist circumference, and body fat percentage45.

Oral supplementation with probiotics has proven effective in improving the risk of developing atherosclerosis, reducing LDL cholesterol and total cholesterol levels, as well as optimizing body composition, body weight, and visceral fat42,46. Furthermore, probiotics have antibacterial properties and enhance the gut barrier and immunomodulatory functions, making them beneficial in regulating the gut microbiota and managing obesity and associated diseases45

Prebiotics

Prebiotics are food components that are indigestible but can positively affect the host's health by selectively stimulating the growth or activity of specific gut bacteria, thereby improving host health46 Additionally, they can serve as a medium for probiotics, promoting their growth. Examples of prebiotics include inulin, lactulose, fructooligosaccharides, and derivatives of galactose and β-glucans, which could be considered future tools for combating obesity. Oligosaccharides, fructooligosaccharides (FOS), galactooligosaccharides (GOS), and polyphenols are the most widespread prebiotics47

Animal studies have shown that prebiotics, such as fructooligosaccharides and galactooligosaccharides, can alter the gut microbiome composition, increase the number of beneficial bacteria like Bifidobacterium and Lactobacillus , and consequently reduce body weight and fat tissue48,49. Moreover, in humans, prebiotics have also been associated with improvements in gut barrier function and metabolic parameters, including insulin resistance50

Studies investigating prebiotics have shown that these compounds promote positive changes in the composition and function of the gut microbiome. By increasing the number of Bifidobacterium species and other butyrate producers, prebiotics contribute to improved metabolic functions and strengthening the gut barrier against pathogens51,52. Inulin, as a fermentable carbohydrate, can increase the density of cells producing the hormone PYY, which suppresses appetite by 8%, thereby contributing to reduced food intake and potentially playing an important role in the treatment of obesity. Additionally, supplementation with GOS in healthy individuals has been shown to increase the number of beneficial Bifidobacterium species while simultaneously reducing the presence of Bacteroides53

Furthermore, individual studies indicate that an increase in Bifidobacterium following the addition of FOS can be accompanied by the growth of Lactobacillus species, resulting in a decrease in ghrelin levels, PYY, and overall food intake52,53. The same studies also found that discontinuing prebiotic consumption led to a decrease in Lactobacillus species and changes in certain butyrate-producing microbes such as Faecalibacterium, Ruminococcus, and Oscillospira . The research results showed enhanced microbial diversity and beneficial effects on host health due to prebiotic consumption.

In addition, some studies suggest the prebiotic potential of flavanols from cocoa, dark chocolate (DC), and lycopene, and their impact on the gut microbiome composition. Research conducted on obese subjects revealed that one month of lycopene consumption, either alone or combined with DC, resulted in significant changes in the gut microbiome. A dose-dependent increase in Bifidobacterium species was observed with lycopene supplementation, while Lactobacillus species increased with DC intake. Furthermore, both formulations resulted in a decrease in the Bacteroides genus54

Although these findings suggest potential benefits for the gut microbiome, there is currently insufficient evidence to confirm their significant effect on weight loss.

The impact of other factors on obesity and the gut microbiome

In addition to diet, physical activity can also influence the composition of the gut microbiome55. Physical activity promotes the growth of beneficial bacteria such as Staphylococcus hominis and Akkermansia muciniphila , which are positively associated with health55

A study by Allen et al. (2018) examined the impact of physical activity on the gut microbiome in lean and obese individuals with a sedentary lifestyle. Participants engaged in a six-week endurance exercise program, which included 30 to 60 minutes of moderate to intense activity. Stool samples were collected before and after the intervention to analyze changes in the microbiota56

It was observed that physical activity alters the gut microbiome, with differences noted based on obesity status. In lean participants, there was an increase in fecal short-chain fatty acids (SCFAs), such as acetate and butyrate, whereas no such effect was observed in obese participants. Nevertheless, exercise resulted in a reduction in body fat percentage in both groups.

In recent years, therapeutic interventions aimed at modulating the gut microbiome have been developed as a potential approach for treating obesity and related disorders. One such approach is fecal microbiota transplantation (FMT), which is considered an extremely effective method57 .

FMT involves transferring the composition of the gut microbiota from a healthy donor to the patient’s gastrointestinal tract, typically through duodenal endoscopy or colonoscopy, with the goal of normalizing the structure and function of the gut microbial community. The compatibility between the donor and the recipient must be considered, as it is crucial for the successful establishment of the donor's microbial strains in the recipient’s gut. FMT has shown over 90% effectiveness in treating Clostridiumdifficile infections57

Conclusion

Research shows that while healthy adults have a relatively stable and balanced gut microbiome, individuals with diet-induced obesity exhibit significant variations in their microbiome composition compared to individuals with normal body weight.

Changes in the gut microbiome of obese individuals, including an increased ability to extract energy from food and a reduction in bacterial species diversity, may contribute to the development of metabolic disorders. On the other hand, dietary interventions, especially those focusing on increased fiber, prebiotics, and probiotics intake, have proven effective tools for modulating the microbiome and improving metabolic health. In addition to diet, physical activity positively influences the microbiome by promoting the growth of beneficial bacteria associated with health. New therapeutic approaches, such as fecal microbiota transplantation (FMT), also open possibilities for innovative treatments for obesity.

In conclusion, physical activity induces structural and functional changes in the human gut microbiome, with these changes conditioned by obesity status and continuous exercise, regardless of dietary habits. However, it is still uncertain whether exercise confers health benefits by modifying the gut microbiome, as well-designed controlled trials are lacking. Given its observed satisfactory effects, FMT is expected to have potential as a therapy for restoring and improving gut microbiome functionality, which could help treat various diseases related to gut dysbiosis. These include chronic constipation, irritable bowel syndrome, Crohn’s disease, and ulcerative colitis. Additionally, increasing research suggests that FMT may also have potential in treating obesity and related disorders, including type 2 diabetes. Due to its numerous effects on human health, Akkermansia muciniphila is considered a promising prebiotic for improving obesity outcomes.

Ultimately, the approach to obesity must be multidisciplinary, involving changes in lifestyle, diet, and targeted interventions on the gut microbiome to achieve long-term sustainable results in weight management and reduction of metabolic disease risk. Focusing on the composition of the gut microbiome may represent a promising treatment for obesity. However, further research is needed to confirm the effects and effectiveness of this therapeutic approach.

References:

1 Asadi A, Shadab Mehr N, Mohamadi MH, Shokri F, Heidary M, Sadeghifard N, Khoshnood S. Obesity and gut-microbiota-brain axis: A narrative review. J Clin Lab Anal. 2022 May;36(5):e24420. doi: 10.1002/jcla.24420. Epub 2022 Apr 14. PMID: 35421277; PMCID: PMC9102524.

2 WHO – World Health Organization (2021b) WHO Guideline on the integrated management of children and adolescents with obesity: a primary health care approach, World Health Organization, https://www.who.int/news-room/articles-detail/ call-for-experts-who-guideline-development-group-treatmentof-children-and-adolescents-with-obesity. Pristupljeno 20. veljače 2025.

3 V Calcaterra, H Cena, V Rossi, S Santero, A Bianchi, G Zuccotti (2023) Ultra-Processed Food, Reward System and Childhood Obesity. Children (Basel) 10, 804. doi: 10.3390/children10050804.

4 V Rahelić (2021) Uloga nutritivne intervencije u multidisciplinarnom pristupu liječenja pretilosti u djece i adolescenata. Doktorska disertacija. Zagreb: Sveučilište u Zagrebu, Prehrambeno-biotehnološki fakultet.

5 WHO-World Health Organization (2021a) Obesity and overweight, World Health Organization, https://www.who.int/news-room/ fact-sheets/detail/obesity-and-overweight. Pristupljeno 20. veljače 2025.

6 L. Crovesy, M. Ostrowski, D.M.T.P. Ferreira, E.L. Rosado, M. Soares-Mota (2017). Effect of Lactobacillus on body weight and body fat in overweight subjects: a systematic review of randomized controlled clinical trials. Int. J. Obes., 41 (11), 1607-1614.

7 B.A. Peters, J.A. Shapiro, T.R. Church, G. Miller, C. Trinh-Shevrin, E. Yuen, C. Friedlander, R.B. Hayes, J. Ahn (2018). A taxonomic signature of obesity in a large study of American adults. Sci. Rep., 8 (1), 9749.

8 C.L. Boulangé, A.L. Neves, J. Chilloux, J.K. Nicholson, M.E. Dumas (2016). Impact of the gut microbiota on inflammation, obesity, and metabolic disease. Genome Med., 8 (1), 42.

9 Asadi A, Shadab Mehr N, Mohamadi MH, Shokri F, Heidary M, Sadeghifard N, Khoshnood S. Obesity and gut-microbiota-brain axis: A narrative review. J Clin Lab Anal. 2022 May;36(5):e24420. doi: 10.1002/jcla.24420.

10 J. Liang, M. Zhang, X. Wang, Y. Ren, T. Yue, Z. Wang, Z. Gao (2021). Edible fungal polysaccharides, the gut microbiota, and host health. Carbohydr. Polym., 273, Article 118558.

11 H. Tilg, N. Zmora, T.E. Adolph, E. Elinav (2020). The intestinal microbiota fuelling metabolic inflammation. Nat. Rev. Immunol., 20 (1), 40-54.

12 H.Y. Cheng, M.X. Ning, D.K. Chen, W.T. Ma (2019). Interactions between the gut microbiota and the host innate immune response against pathogens. Front. Immunol., 10, 607.

13 S. Lynch, O. Pedersen (2016). The human intestinal microbiome in health and disease N. Engl. J. Med., 375 (24), 2369-2379

14 L.B. Thingholm, M.C. Rühlemann, M. Koch, B. Fuqua, G. Laucke, R. Boehm, C. Bang, E.A. Franzosa, M. Hübenthal, A. Rahnavard, F. Frost, J. Lloyd-Price, M. Schirmer, A.J. Lusis, C.D. Vulpe, M.M. Lerch, G. Homuth, T. Kacprowski, C.O. Schmidt, U. Nöthlings, T.H. Karlsen, W. Lieb, M. Laudes, A. Franke, C. Huttenhower (2019). Obese individuals with and without type 2 diabetes show different gut microbial functional capacity and composition. Cell Host Microbe, 26 (2), 252-264.

15 C.B. de La Serre, C.L. Ellis, J. Lee, A.L. Hartman, J.C. Rutledge, H.E. Raybould

16 D. Chen, Z. Yang, X. Chen, Y. Huang, B. Yin, F. Guo, H. Zhao, J. Huang, Y. Wu, R. Gu (2015). Effect of Lactobacillus rhamnosus hsryfm 1301 on the gut microbiota and lipid metabolism in rats fed a high-fat diet. J. Microbiol. Biotechnol., 25 (5), 687-695.

17 K.A. Kim, W. Gu, I.A. Lee, E.H. Joh, D.H. Kim (2012). High fat diet-induced gut microbiota exacerbates inflammation and obesity in mice via the TLR4 signaling pathway PLoS One, 7 (10), Article e47713.

18 M.K. Hamilton, G. Boudry, D.G. Lemay, H.E. Raybould (2015). Changes in intestinal barrier function and gut microbiota in high-fat diet-fed rats are dynamic and region dependent. Am. J. Physiol. Gastrointest. Liver Physiol., 308 (10), G840-G851.

19 M. Million, M. Maraninchi, M. Henry, F. Armougom, H. Richet, P. Carrieri, R. Valero, D. Raccah, B. Vialettes, D. Raoult (2012). Obesity-associated gut microbiota is enriched in Lactobacillus reuteri and depleted in Bifidobacterium animalis and Methanobrevibacter smithii. Int. J. Obes., 36 (6), 817-825.

20 B. Wei, Y. Wang, S. Xiang, Y. Jiang, R. Chen, N. Hu (2021). Alterations of gut microbiome in patients with type 2 diabetes mellitus who had undergone cholecystectomy. Am. J. Physiol. Endocrinol. Metab., 320 (1), E113-E121.

21 K.M. Utzschneider, et al. (2016). Mechanisms linking the gut microbiome and glucose metabolism (vol. 101, pg 1445, 2016). J. Clin. Endocrinol. Metab., 101 (6), 2622-2622.

22 L. Brunkwall, M. Orho-Melander (2017). The gut microbiome as a target for prevention and treatment of hyperglycaemia in type 2 diabetes: from current human evidence to future possibilities. Diabetologia, 60 (6), 943-951.

23 G Jiafeng, N Qingqiang, S Wei, L Liangge F Xiujing (2022). The links between gut microbiota and obesity and obesity related diseases. Biomed. Pharmacother., 147, 112678.

24 A. Beam, E. Clinger, L. Hao (2021). Effect of diet and dietary components on the composition of the gut microbiota. Nutrients, 13 (8), 2795.

25 K.E. Bouter, D.H. van Raalte, A.K. Groen, M. Nieuwdorp (2017). Role of the gut microbiome in the pathogenesis of obesity and obesity-related metabolic dysfunction Gastroenterology, 152 (7), 1671-1678.

26 L.H.S. Lau, S.H. Wong (2018). Microbiota, obesity and NAFLD. Adv. Exp. Med. Biol., 1061, 111-125.

27 A. Pascale, N. Marchesi, C. Marelli, A. Coppola, L. Luzi, S. Govoni, A. Giustina, C. Gazzaruso (2018). Microbiota and metabolic diseases. Endocrine, 61 (3), 357-371.

28 J. Zimmer, B. Lange, J.S. Frick, H. Sauer, K. Zimmermann, A. Schwiertz, K. Rusch, S. Klosterhalfen, P. Enck (2012). A vegan or vegetarian diet substantially alters the human colonic faecal microbiota. Eur. J. Clin. Nutr., 66 (1), 53-60.

29 Y. Fan, O. Pedersen (2021). Gut microbiota in human metabolic health and disease. Nat. Rev. Microbiol., 19 (1), 55-71.

30 L. Crovesy, M. Ostrowski, D.M.T.P. Ferreira, E.L. Rosado, M. Soares-Mota (2017). Effect of Lactobacillus on body weight and body fat in overweight subjects: a systematic review of randomized controlled clinical trials. Int. J. Obes., 41 (11), 1607-1614.

31 X. Gao, Y. Zhu, Y. Wen, G. Liu, C. Wan (2016). Efficacy of probiotics in non-alcoholic fatty liver disease in adult and children: a meta-analysis of randomized controlled trials. Hepatol. Res., 46 (12), 1226-1233.

32 Aoun A, Darwish F, Hamod N. The Influence of the Gut Microbiome on Obesity in Adults and the Role of Probiotics, Prebiotics, and Synbiotics for Weight Loss. Prev Nutr Food Sci. 2020 Jun 30;25(2):113-123. doi: 10.3746/pnf.2020.25.2.113

33 De Filippo C, Cavalieri D, Di Paola M, Ramazzotti M, Poullet JB, Massart S, Collini S, Pieraccini G, Lionetti P. Impact of diet in shaping gut microbiota revealed by a comparative study in children from Europe and rural Africa. Proc Natl Acad Sci U S A. 2010 Aug 17;107(33):14691-6. doi: 10.1073/pnas.1005963107

34 Aoun A, Darwish F, Hamod N. The Influence of the Gut Microbiome on Obesity in Adults and the Role of Probiotics, Prebiotics, and Synbiotics for Weight Loss. Prev Nutr Food Sci. 2020 Jun 30;25(2):113-123. doi: 10.3746/pnf.2020.25.2.11

35 H.Y. Li, D.D. Zhou, R.Y. Gan, S.Y. Huang, C.N. Zhao, A. Shang, X.Y. Xu, H.B. Li (2021). Effects and mechanisms of probiotics, prebiotics, synbiotics, and postbiotics on metabolic diseases targeting gut microbiota: a narrative revie. Nutrients, 13 (9) (2021), 3211.

36 Asadi A, Shadab Mehr N, Mohamadi MH, Shokri F, Heidary M, Sadeghifard N, Khoshnood S. Obesity and gut-microbiota-brain axis: A narrative review. J Clin Lab Anal. 2022 May;36(5):e24420. doi: 10.1002/jcla.24420.

37 Aoun A, Darwish F, Hamod N. The Influence of the Gut Microbiome on Obesity in Adults and the Role of Probiotics, Prebiotics, and Synbiotics for Weight Loss. Prev Nutr Food Sci. 2020 Jun 30;25(2):113-123. doi: 10.3746/pnf.2020.25.2.113.

38 T. Cerdó, J.A. García-Santos, M. G Bermúdez, C. Campoy (2019). The role of probiotics and prebiotics in the prevention and treatment of obesity. Nutrients, 11 (3).

39 P. Gerard (2016). Gut microbiota and obesity. Cell. Mol. Life Sci., 73 (1), 147-162.

40R. Luoto, M. Kalliomäki, K. Laitinen, E. Isolauri (2010). The impact of perinatal probiotic intervention on the development of overweight and obesity: follow-up study from birth to 10 years. Int. J. Obes., 34 (10), 1531-1537.

41 G Jiafeng, N Qingqiang, S Wei, L Liangge F Xiujing (2022). The links between gut microbiota and obesity and obesity related diseases. Biomed. Pharmacother., 147, 112678.

42 Y. Kadooka, M. Sato, K. Imaizumi, A. Ogawa, K. Ikuyama, Y. Akai, M. Okano, M. Kagoshima, T. Tsuchida (2010). Regulation of abdominal adiposity by probiotics (Lactobacillus gasseri SBT2055) in adults with obese tendencies in a randomized controlled trial. Eur. J. Clin. Nutr., 64 (6) 636-643.

43 S.P. Jung, K.M. Lee, J.H. Kang, S.I. Yun, H.O. Park, Y. Moon, J.Y. Kim (2013). Effect of Lactobacillus gasseri BNR17 on overweight and obese adults: a randomized, double-blind clinical trial. Korean J. Fam. Med., 34 (2), 80-89.

44 J. Sanchis-Chordà, E. Del Pulgar, J. Carrasco-Luna, A. Benítez-Páez, Y. Sanz, P. Codoñer-Franch (2019). Bifidobacterium pseudocatenulatum CECT 7765 supplementation improves inflammatory status in insulin-resistant obese children. Eur. J. Nutr., 58 (7), 2789-2800.

45 L. Abenavoli, E. Scarpellini, C. Colica, L. Boccuto, B. Salehi, J. Sharifi-Rad, V. Aiello, B. Romano, A. De Lorenzo, A.A. Izzo, R. Capasso (2019). Gut microbiota and obesity: a role for probiotics. Nutrients, 11 (11).

46 H.S. Ejtahed, J. Mohtadi-Nia, A. Homayouni-Rad, M. Niafar, M. Asghari-Jafarabadi, V. Mofid (2012). Probiotic yogurt improves antioxidant status in type 2 diabetic patients. Nutrition, 28 (5), 539-543.

47 P. Gerard (2016). Gut microbiota and obesity. Cell. Mol. Life Sci., 73 (1), 147-162.

48 Asadi A, Shadab Mehr N, Mohamadi MH, Shokri F, Heidary M, Sadeghifard N, Khoshnood S. Obesity and gut-microbiota-brain axis: A narrative review. J Clin Lab Anal. 2022 May;36(5):e24420. doi: 10.1002/jcla.24420

49 A. Adak, M.R. Khan (2019). An insight into gut microbiota and its functionalities. Cell Mol. Life Sci., 76 (3), 473-493.

50 A. Everard, V. Lazarevic, M. Derrien, M. Girard, G.G. Muccioli, A.M. Neyrinck, S. Possemiers, A. Van Holle, P. François, W.M. de Vos, N.M. Delzenne, J. Schrenzel, P.D. Cani (2011). Responses of gut microbiota and glucose and lipid metabolism to prebiotics in genetic obese and diet-induced leptin-resistant mice. Diabetes, 60 (11), 2775-2786.

51 J.A. Parnell, R.A. Reimer (2009). Weight loss during oligofructose supplementation is associated with decreased ghrelin and increased peptide YY in overweight and obese adults. Am. J. Clin. Nutr., 89 (6), 1751-1759.

52 Yoo S, Jung SC, Kwak K, Kim JS. The Role of Prebiotics in Modulating Gut Microbiota: Implications for Human Health. Int J Mol Sci. 2024 Apr 29;25(9):4834. doi: 10.3390/ijms25094834

53 Krumbeck JA, Rasmussen HE, Hutkins RW, Clarke J, Shawron K, Keshavarzian A, Walter J. Probiotic Bifidobacterium strains and galactooligosaccharides improve intestinal barrier function in obese adults but show no synergism when used together as synbiotics. Microbiome. 2018 Jun 28;6(1):121. doi: 10.1186/ s40168-018-0494-4

54 Wiese M, Bashmakov Y, Chalyk N, Nielsen DS, Krych Ł, Kot W, Klochkov V, Pristensky D, Bandaletova T, Chernyshova M, Kyle N, Petyaev I. Prebiotic Effect of Lycopene and Dark Chocolate on Gut Microbiome with Systemic Changes in Liver Metabolism, Skeletal Muscles and Skin in Moderately Obese Persons. Biomed Res Int. 2019 Jun 2;2019:4625279. doi: 10.1155/2019/4625279.

55 C. Bressa, M. Bailén-Andrino, J. Pérez-Santiago, R. González-Soltero, M. Pérez, M.G. Montalvo-Lominchar, J.L. Maté-Muñoz, R. Domínguez, D. Moreno, M. Larrosa (2017). Differences in gut microbiota profile between women with active lifestyle and sedentary women. PLoS One, 12 (2), Article e0171352.

56 Allen JM, Mailing LJ, Niemiro GM, Moore R, Cook MD, White BA, Holscher HD, Woods JA. Exercise Alters Gut Microbiota Composition and Function in Lean and Obese Humans. Med Sci Sports Exerc. 2018 Apr;50(4):747-757. doi: 10.1249/MSS.0000000000001495.

57 P. de Groot, T. Scheithauer, G.J. Bakker, A. Prodan, E. Levin, M.T. Khan, H. Herrema, M. Ackermans, M.J.M. Serlie, M. de Brauw, J.H.M. Levels, A. Sales, V.E. Gerdes, M. Ståhlman, A.W.M. Schimmel, G. Dallinga-Thie, J.J. Bergman, F. Holleman, J.B.L. Hoekstra, A. Groen, F. Bäckhed, M. Nieuwdorp (2020). Donor metabolic characteristics drive effects of faecal microbiota transplantation on recipient insulin sensitivity, energy expenditure and intestinal transit time. Gut, 69 (3), 502-512