Overweight and obesity are related pathological conditions with a significant impact at the cardiovascular, metabolic, musculoskeletal, and oncological levels, representing a significant global public health problem. The traditionally proposed therapeutic approaches act at the nutritional, psychological, lifestyle (abolishing sedentary lifestyle and promoting physical exercise), and pharmacological levels, in combination with the consumption of food supplements.
Overweight and obesity are related pathological conditions with a significant impact at the cardiovascular, metabolic, musculoskeletal, and oncological levels, representing a significant global public health problem . The traditionally proposed therapeutic approaches act at the nutritional, psychological, lifestyle (abolishing sedentary lifestyle and promoting physical exercise), and pharmacological levels, in combination with the consumption of food supplements . Watanabe et al. recently identified and examined 33 food supplements most used for weight loss, dividing them according to the main effect and depending on the primary impact on nutrient absorption, appetite regulation, energy expenditure modulation, and fat and carbohydrate metabolism . Substances considered prebiotic, which specifically stimulate components of the microbiota capable of providing positive effects, such as increasing immune function and protection from pathogens, improve host metabolism and nutrient absorption . This can have a significant impact on the metabolism of various substances used as food supplements.
The retrieved data indicated that many different food supplements, both herbal and not, have been investigated in humans for their prebiotic effect and their capacity to modulate gut microbiota. (Table 1). In detail, we found robust data for the following: Supplements with the main goal of nutrient absorption (green tea, ginseng, chitosan, β-glucans, psyllium, guar gum, and inulin); Supplements with the main goal of appetite regulation (whey proteins and chlorogenic acid); Supplements with the main goal of energy expenditure modulation (curcumin and L-carnitine); Supplements with the main goal of fat metabolism (resveratrol and flaxseed).
Table 1. Summary of clinical trials reporting prebiotic effects of these natural substances and their impact on gut microflora.
|Substance||Subjects||Intervention||Clinical Outcome||Gut Microflora
|Substances with Evidence of Weight Loss Associated with Modifications of the Microbiota|
|Chlorogenic Acid ||26 patients with diabetes and non-alcoholic fatty liver disease (NAFLD)||3 months of 200 mg caffeine plus 200 mg chlorogenic acid supplementation||Significant decrease in body weight||Non-significative bifidobacteria increase in the caffeine plus chlorogenic acid group|
|Inulin ||44 healthy adults with mild constipation||12 g/day inulin intake||Gut function improvement||Changes in relative abundances of Anaerostipes, Bilophila, and Bifidobacterium spp.|
|26 healthy individuals||9 g/die inulin intake||Greater satiety||Greater proportions of the genus Bifidobacterium, a reduced level of non-classified Clostridiales. and a tendency to decrease Oxalobacteraceae|
|30 obese women||Inulin/oligofructose 50/50 mix 16 g/day for 3 months||Slight decrease in fat mass and plasma levels of lactate and phosphatidylcholine||Bifidobacterium spp. and Faecalibacterium prausnitzii increase and Bacteroides intestinalis, Bacteroides vulgatus. and Propionibacterium spp. reduction|
|12 overweight adults||20 g/day of inulin-propionate ester||Increase in Actinobacteria, decrease in Clostridia; decrease in the proportion of Clostridiales order. Anaerostipes hadrus, Bifidobacterium faecale. Bacteroides caccae, Bacteroides uniformis, Bacteroides xylanisolvens, and Fusicatenibacter saccharivorans higher percentage and a lower percentage of Blautia obeumin, Blautia lutea and Bacillius fluminis, Blautia obeum, Eubacterium ruminantium, Anaerostipes hadrus, and Prevotella copri|
|42 12-year-old overweight subjects||8 g/day of oligofructose enriched inulin for 16 weeks||Significant decreases in body weight and serum triglycerides||Bifidobacterium spp. increase and decrease in Bacteroides vulgatus and Faecalibacterium prausnitzii|
|P. ginseng ||10 obese women||8 g dry extract for 8 weeks||Weight loss effect and slight modifications of gut microbiota||In effective weight loss group, change in levels of Blautia, Faecalibacterium spp. In ineffective weight loss group, change in levels of Bifidobacterium, Blautia, and Clostridium at the genus level|
|Substances with Evidence of Metabolic Modifications Potentially Favorable to Weight Loss Associated with Modifications of the Microbiota|
|Resveratrol (RSV) ||37 overweight and obese men and women||Supplementation of epigallocatechin-3-gallate and RSV (282 and 80 mg/day, respectively, for 12 weeks)||Increased fat oxidation and skeletal muscle mitochondrial oxidative capacity||Reduced abundance of Bacteroidetes phylum in men but not in women|
|Flaxseed ||58 obese postmenopausal women||Flaxseed mucilage (10 g) for 6 weeks||Improved insulin sensitivity related to the decrease in the serum C-peptide and insulin response||24 decreased species in Faecalibacterium genus and 8 increased species in Clostridium genus|
|Substances with Evidence of Changes in the Microbiota Associated with Other Effects (Which in the Animal Model are Associated with Weight Loss)|
|β-glucans ||26 healthy subjects||2 months of 3 g/day of barley β-glucans||Marked increase in levels of the main SCFA||Increased levels of Roseburia hominis, Clostridiaceae (Clostridium orbiscindens and other Clostridium spp.), Ruminococcus spp. and reduced abundance of Firmicutes and Fusobacteria|
|Chitosan and COS ||10 healthy volunteers||3 g chitosan/day before meal for 28-day supplement period||Increased level of Bacteroides spp.|
|120 Chinese coronary heart disease patients||COS consumption of 1-2 g/day for 6 months||Improved blood urea nitrogen and serum creatinine. Higher circulating antioxidant levels.
Increased SOD and GSH serum levels. Reduced levels of ALT and AST. Improved lipid profiles
|Decreased Faecalibacterium, Alistipes, and Escherichia spp. abundance. Bacteroides, Megasphaera, Roseburia, Prevotella, and Bifidobac-terium spp., increased abundance of Lactobacillus, Lactococcus, and Phascolarctobacterium spp.|
|Curcumin ||30 healthy subjects (14 analyzed)||1000 mg curcumin plus 1.25 mg extract of piperine every tablet—3 times/day||Increase in Clostridium, Bacteroides., Citrobacter, Cronobacter, Enterobacter, Enterococcus, Klebsiella, Parabacteroides, and Pseudomonas spp. and decreased abundance of Blautia and Ruminococcus spp.|
|Green Tea ||Healthy subjects: 8 males, 4 females||400 mL per day for two weeks||Elevation in SCFA, and reduction in bacterial LPS synthesis in feces||Increased Firmicutes to Bacteroidetes ratio, reduced fecal levels of Fusobacterium spp.|
|Guar Gum ||20 healthy volunteers||5 g of guar gum three times/day for 3 weeks||Improvement in defecation frequency; stool consistency; and abundance of butyrate, acetate, and amino acids||Increase in Ruminococcus, Fusicatenibacter, Faecalibacterium, and Bacteroides spp. and a reduction in Roseburia, Lachnospiracea, and Blautia spp.|
|44 healthy volunteers||5 g/day guar gum for 3 months||Altered stool consistency||Bifidobacterium, Ruminococcus, and Megasphaera spp. increase and Bacteroides and Phascolarctobacterium spp. inhibited growth|
|31 healthy volunteers||3.4 g/day guar gum for 21 days||Transitory bifidobacterial increase|
|13 children suffering from autism spectrum disorder with concomitant dysbiosis and constipation||6 g/day guar gum||Increased defecation frequency and reduced irritability||Increased Acidaminococcus spp. and reduced genera Streptococcus, Odoribacter, and Eubacterium spp.|
|15 hemodialysis patients with concomitant constipation||5.1 g/day guar gum for 4 weeks||Improved the individual stool form and decreased the constipation||Increase in bifidobacteria, Bacteroides spp. and lactobacilli and reduction in the Clostridium XVIII cluster|
|L-carnitine ||15 Japanese patients receiving hemodialysis||L-carnitine
tablets (900 mg) for 3 months
|Improved muscle discomfort, gastrointestinal disorders||Decrease in the abundance of genus Clostridia subcluster 4|
|Whey Proteins ||24 cross-country runners||10 weeks 20 g isolated WP + 10 g hydrolyzed WP||Increased abundance of Bacteroidetes phylum; decreased presence of health-related taxa, including Roseburia, Blautia spp., and Bifidobacterium longum|
|Psyllium ||8 healthy volunteers and 16 constipated patients||7 days of 7 g/day psyllium||Increased acetate, propionate, and butyrate, correlated with increased fecal water||Healthy adults increased Veillonella and decreased
Subdoligranulum spp. In constipated subjects, increased levels of Lachnospira, Faecalibacterium, Phascolarctobacterium, Veillonella, and Sutterella spp., decreased uncultured Coriobacteria and Christensenella spp.
The evaluation of the effectiveness and related biological mechanisms of natural products mainly used in the management of overweight depicts different targets and underlined mechanisms, including carbohydrate and fat metabolism and/or increased energy expenditure. Interestingly, current evidence suggests that the modulation of gut microflora provided by some nutraceuticals and herbal food supplements may play a relevant role in intestinal homeostasis. The analysis performed in this review underlines the effect on overweight and related pathological conditions exerted by nutraceuticals and herbal food supplements intervening in the gut microbiota structure and their reshaping abilities. In particular, this work highlights the complexity of specific modifications of the microbial environment produced by natural products. It is worth noting that in a recent review, which comprehensively took into account the most used food supplements for the management of overweight , all natural products with a demonstrated prebiotic effect were included. In vivo and in vitro studies have evidenced a prebiotic effect of top selling food supplements, such as white kidney bean, glucomannan, agar, caralluma, spirulina, coffee/caffeine/guaranà, bitter orange, capsaicin, capsaicinoids and capsinoids, pyruvate, dyacilglycerol, liquorice, conjugated linoleic acid, aloe vera, grapefruit, mangosteen, chromium and lipoic acid, whereas more sound data could be retrieved for some natural products investigated in clinical trials. This review depicts the up-to-date state of the art of the fascinating complexity of gut microbiota modulation exerted by nutraceuticals and herbal food supplements investigated in clinical trials. Some of these substances have been shown to be able to act on Bifidobacterium; Lactobacillus; Akkermansia; and productive butyrate species, such as Faecalibacterium and Roseburia spp. The ability to favor the development of bifidobacteria is considerably relevant for a series of different effects, including the immuno-modulation processes and protection against pathogens; cross-talk with the butyrate producers, such as Faecalibacterium prausnitzii and Roseburia spp.; and the ability to intervene in the metabolism of macro- and micronutrients with lysis of indigestible carbohydrates, vitamin B group synthesis and antioxidants substances . Furthermore, the ability to positively modulate butyrate-producing bacteria potentially confers other metabolic benefits, favoring the modulation of adipose organ function, liver and skeletal muscle function, with the amelioration of glucose levels and improved insulin sensitivity . The upregulation of Lactobacillus spp. is a potentially favorable element in the management of various conditions, such as the health maintenance of reproductive  and urological  systems. Crovesy et al. also described numerous benefits in relation to weight control for different Lactobacillus spp., both taken individually and combined with other nutraceutical products. . Several nutraceuticals show the ability to favor the modulation of Akkermansia muciniphila , a strain actively investigated in recent years. Akkermansia muciniphila is related to a series of extremely favorable effects in the context of weight control, reduction in body fat, and the management of many of metabolic problems. Everard et. al. reported that Akkermansia muciniphila can act by increasing endocannabinoids gut levels, which play a relevant role in inflammation, gut barrier and gut peptide secretion, reverting fat-mass gain, adipose tissue inflammation, insulin resistance, and metabolic endotoxemia . Xu et al. proposed that Akkermansia muciniphila also intervenes favorably in the modulation of liver and metabolic disorders related to lipid metabolism, modifying the metabolic pathways present in an obesity condition . Abuqwider et. al, starting from the analysis of 804 studies, focused on 10 randomized controlled trials that showed that Akkermansia muciniphila balances the dynamics of energy management, favoring a better balance of carbohydrate metabolism with a consequent reduction in low-grade inflammatory processes, and contributed to weight management and to the improvement of the metabolic parameters related to obesity . Faecalibacterium prausnitzii and Rosaeburia spp. are described as being the main producer of butyrate , an essential short chain fatty acid for maintaining gut homeostasis and intestinal barrier function. Their presence is correlated with a better management of inflammatory processes and immune tolerance, especially in allergy-based disorders .