The industrialization of European countries has resulted in an increased amount of fat in our diet, and a reduction in complex carbohydrate consumption, which has led to a decrease in gut microbiome diversity [10]. It was found that African children from rural villages, in contrast to European populations, showed a significant enrichment in phylum Bacteroidetes and a depletion in Firmicutes, and the family of Enterobacteriaceae from the phylum Proteobacteria, with a unique abundance of bacteria from the genera Prevotella and Xylanibacter. The latter contains a set of bacterial genes for cellulose and xylan hydrolysis that are completely missing in European children [10]. Furthermore, their diet was rich in short-chain fatty acids [10]. Differences in the gut microbiome and metabolomics profile between unindustrialized, traditional rural lifestyles (Hadza hunter-gatherers of Tanzania) and the industrialized, Westernized diet and lifestyles of urban Italians were found [10,11,12,13]. The Hadza diet consists of wild foods that can be classified into five main categories: meat, honey, baobab, berries and tubers, without cultivated or domesticated plants and animals, and minimal amounts of agricultural products, whereas the diet of the Italian cohort is almost entirely composed of commercial agricultural products and adheres to the Mediterranean diet, which includes abundant plant foods, fresh fruit, pasta, bread and olive oil [11]. The study revealed higher abundance of Bacteroidetes and a lower abundance of Firmicutes in the Hadza population compared to the Italian group, and the near absence of Actinobacteria, an important subdominant component, in the Italian microbiome [11]. Furthermore, the Hadza gut microbial ecosystem was profoundly depleted in Bifidobacterium, enriched in Prevotella, and comprised of unusual arrangement of Clostridiales [11]. Moreover, a review by García-Montero et al. did not compare specific diets related to particular environmental factors but rather nutritional approaches such as the Mediterranean and Westernized diet [14]. Based on a PREDIMED (PREvención con DIeta MEDiterránea) study, the authors concluded that participants with better adherence to the Mediterranean diet, who consumed more polysaccharides and plant proteins and less animal protein [15] and those with reduced animal protein in their diet, presented a higher abundance of Bacteroidetes with a lower Firmicutes/Bacteroidetes ratio [14,15]. This diet pattern was related to greater diversity, and an improved gut barrier function and permeability [16]. Participants who consumed greater amounts of animal protein differed from the Mediterranean diet and were characterized by a higher Firmicutes/Bacteroidetes ratio [14,15].

The Westernized diet is characterized by a high content of unhealthy and harmful elements along with a reduced consumption of fruits and vegetables. This dietary approach promotes a pathological microbiota status, leading to a higher Firmicutes/Bacteroidetes ratio [14].

The relationships between dietary fat and health are complex. On the one hand, diets high in saturated and trans fatty acids increase the risk of cardiovascular diseases via the up-regulation of total blood cholesterol and LDL-cholesterol [20]. On the other hand, mono- and polyunsaturated fats are beneficial to our health.

The contribution of the gut microbiome to fat metabolism is multidirectional. Gut microbiota (such as Eubacterium and Bacteroides) are proven to participate in the conversion of cholesterol to coprostanol, which is a non-absorbable sterol excreted in the feces. Two major pathways have been proposed for this process. The first involves a direct reduction in the 5–6 double bond in cholesterol, while the second consists of the oxidation of the 3β-hydroxy group and the isomerization of the double bond to yield 4-cholesten-3-one, which undergoes two reductions to form coprostanone and then coprostanol [21]. Furthermore, diets rich in fats stimulate the production of bile acids that, in addition to their role in the absorption of dietary lipids and lipid-soluble nutrients, exhibit antimicrobial activity and promote microbiome species capable of metabolizing bile acids in the intestine [21]. Microbiota also participates in the transformation of primary bile acid to secondary bile acid via the deconjugation, oxidation and epimerization of hydroxyl groups at C3, C7 and C12, 7-dehydroxylation, esterification and desulfatation [21]. Different secondary bile acids can influence health in various ways [21].

The human diet is important for the gut microbiome composition in both adult life and during childhood and even before birth. A study by Chu et al. revealed that, independent of maternal body mass index, a maternal high-fat diet is associated with distinct changes in the neonatal gut microbiome at birth, which persists through 4–6 weeks of age [22]. The study showed that a diet rich in fat caused a reduction in the Bacteroides species in the infant gut [22]. These microbes are responsible for the polysaccharide metabolism, including for the production of short-chain fatty acids from human milk oligosaccharides, which is a major energy source for rapidly growing infants [23] and affects their immune development [23]. Higher dietary fat content also resulted in an increase in Firmicutes, Proteobacteria and Actinobacteria in mice [24,25,26,27]. The data concerning Bacteroidetes in the context of a fat rich diet are ambiguous [24,26,28]. This might be related to the fact that, as shown by Wu et al., among Bacteroidetes, Bacteroides species are associated with long-term proteins and animal-fat consumption, whereas increased levels of Prevotella were found in patients with diets high in carbohydrates, especially fiber [29]. Furthermore, it was proven that a high-fat diet increased the abundance of Gram-negative bacteria [30].

Additionally, a meta-analysis based on 27 dietary studies, including 1,101 samples from rodents and humans in a finer taxonomic analysis, revealed that the most reproducible signals of a high-fat diet are Lactococcus species (Firmicutes), which were demonstrated to be common dietary contaminants [31]. Furthermore, in this study, the Firmicutes/Bacteroidetes ratio was significantly correlated with fat content [31] (Figure 1).

Dietary proteins are considered to be one of the most important macronutrients. They are digested to produce amino acids, which are used for protein synthesis. They have many important functions in the human body, including in the cardiovascular system, for instance, for transport (hemoglobin) and muscle contraction (actin, myosin). The undigested proteins and amino acids are mainly fermented by bacteria into various metabolites, such as organic amines, hydrogen sulfate and ammonia, both of which participate in various physiological functions related to host health and diseases. Greater levels of undigested proteins lead to an increase in pathogenic microorganism with an associated higher risk of metabolic diseases [71]. Both the origin of the protein (animal vs. plant) and its concentration can influence the gut microbiome [71]. It was shown that a diet enriched with 20% peanut protein led to an increase in Bifidobacterium and a reduction in Enterobacteria and Clostridium perfringensa in rats [33]. Furthermore, a higher intake of soybean protein was associated with an increase in Escherichia and Propionibacterium abundance [34,35,36], whereas data from the literature revealed that casein, a protein present in milk, can also increase the abundance of Bifidobacterium and Lactobacilli [37], and decrease the abundance of Staphylococci, Coliformis, Streptococci [38], Eubacterium rectale and Marvinbryantia formatexigens [39]. Moreover, in the study of Garcia-Mantrana I. et al. a higher intake of animal protein was found to be related to a significantly lower presence of Bacteroidetes (p = 0.029) and a higher Firmicutes/Bacteroidetes ratio [15].

Moreover, a randomized, double-blind, parallel-design trial conducted in 38 overweight individuals, who received high-protein isocaloric diets with casein, soy protein or a maltodextrin (control) supplementation, revealed that high-protein diets did not alter the microbiota composition, but induced a shift in bacterial metabolism toward amino acid degradation with different metabolite profiles in accordance with the protein source [72]. Another study suggests that the dietary protein/fat ratio has only minimal, transient effects on the gut microbiota composition; however, gut microbiota might contribute to variability in host responses to high altitude [73]. Moreover, a positive correlation was found between Firmicutes abundance and high concentrations of amino acid degradation products, that might be related to Clostridia activity [74] and a negative correlation was identified for an abundance of Bacteroidetes with the exception for Butyricimonas and Odoribacter genera, both of which showed a positive correlation [72]. A low amount of protein in the diet, by reducing substrate for pathogenic bacteria proliferation, resulted in reduced Escherichia coli abundance on the mucosal surface [75,76,77]. The gut microbiome composition in animal models seems to be strictly associated with the consumption of dietary protein, whereby doses from 100 to 200 g/kg caused an increase in Lactobacilli and a reduction in Coliformis and Staphylococci; doses greater than 200 g/kg caused an increase in Coliforms, Streptococcus and Bacillus [40].

The above-mentioned studies confirm proteins’ role in regulating the gut microbiome; however, the study based on 109 healthy men and women aged 21 to 65, with a body mass index of 18 to 36, revealed that protein is less influential than saturated fat [78].

Daily energy requirements depend on gender, age, height, weight, health, and levels of physical activity. In both the prevention and treatment of cardiovascular diseases, maintaining a particular body weight is extremely important. Carbohydrates, as the main source of energy in the diet, are crucial for energy homeostasis.

Feva et al. studied 88 subjects at an increased risk of metabolic syndrome, who were kept on a high saturated fat diet for 4 weeks (baseline), and were then randomly placed under one of the five experimental diets for 24 weeks [41]. The study revealed that low fat, high carbohydrate diets increased fecal Bifidobacterium and high carbohydrate/high glycemic index increased fecal Bacteroides, whereas high carbohydrate/low glycemic index and a high saturated diet increased Faecalibacterium prausnitzii. Changes in the abundance of fecal Bacteroides correlated inversely with body weight [41]. Another study showed that supplementing the diet with galacto-oligosaccharides increased the abundance of Bifidobacterium species in feces five-fold in obese or overweight people [42].

Furthermore, an analysis conducted on 1135 participants from a Dutch population, using deep sequencing [43], showed that a higher intake of total carbohydrates were most strongly associated with an increase in Bifidobacteria, while they were associated with a decrease in Lactobacillus, Streptococcus, and Roseburia [43]. Lactobacillus and Streptococcus are lactose-fermenting bacteria that, through lactic acid production, lower the gut pH and inhibits amine and benzopyrole production, while Roseburia lead to increasing serum and fecal butyrate levels via the conversion of acetate into butyrate [90].

Data concerning vitamins, the gut microbiome and cardiovascular diseases combined are limited in the literature. Among vitamins, vitamin D is the most widely described in the literature in this context. Although vitamin D has been traditionally recognized as a vitamin responsible for bone–mineral health, its role in hypertension, peripheral artery disease, myocardial infarction and heart failure has also been described [111].

In a cohort of 34 hypertension patients and 15 healthy controls, Zuo et al. suggested that gut microbiome dysbiosis, contributing to the hypertension development, might be partially mediated by vitamin D3 deficiency [112]. Vitamin D3 was significantly decreased in the feces of hypertension patients and correlated with decreased biodiversity, expressed through the Shannon index and Pielou evenness [112]. Moreover, fecal vitamin D3 positively correlated with Subdoligranulum, Ruminiclostridium, Intestinimonas, Pseudoflavonifractor, Paenibacillus, and Marvinbryantia genera from Firmicutes [112]. A recently published article on vitamin D and gut the microbiome includes a study of 567 older men, and identified eight taxa in the Firmicutes phylum that were positively associated with vitamin D metabolites. In the study, men with higher levels of calcitriol and higher calcitriol activation ratios, but not calcifediol, were more likely to possess butyrate-producing bacteria that are associated with better gut microbial health [48] and clinical status.

A recent human study on twenty adults with vitamin D insufficiency or deficiency, who were given 600, 4000 or 10,000 IU/day of oral vitamin D3, revealed that a higher baseline vitamin D concentration was associated with an increased relative abundance of Akkermansia (phylum Verrucomicrobia) and a decreased relative abundance of Porphyromonas (phylum Bacteroidetes), whereas after the intervention, dose-dependent increases in the relative abundance of Bacteroides (phylum Bacteroidetes) and Parabacteroides (phylum Bacteroidetes) were found [113].

For vitamin A, a relationship with formation of congenital heart defects [49], and energy homeostasis [114] were revealed. A study concerning vitamin A and the gut microbiome in mice models showed that mice with a vitamin A-deficient diet had significantly lower butyrate levels and higher acetate levels in the cecum compared to mice with a vitamin A-sufficient diet. The increase in butyrate levels in mice with a vitamin A-sufficient diet corresponded to higher numbers of the butyrate-producing bacteria—Clostridium ramosum (a member of Clostridium_XVIII), than for mice with a vitamin A-deficient diet. Mice with a vitamin A-deficient diet demonstrated disturbances in multiple metabolic pathways, including alterations in energy homeostasis [114]. Furthermore, a PICRUSt analysis revealed that bacteria from vitamin A-sufficient mice resulted in the enrichment of genes that are important in the biosynthesis of some amino acids, including phenylalanine, tyrosine, tryptophan, and lysine, while bacterial communities from vitamin A-insufficient mice had an enhanced carbohydrate and amino acid metabolism [114] (Figure 5).

Moreover, studies on vitamin B12 indicated that supplementation with cobalamin and whey increased Bacteroidetes/Firmicutes ratio and reduced Proteobacteria spp. abundance (Escherichia/Shigella spp. and Pseudomonas) [50]. In the study, cobalamin was found to enhance the growth of Bacteroidetes; meanwhile whey protein promoted the growth of Firmicutes [50].

In mice models, the low-vitamin E group was characterized with higher Firmicutes/Bacteroidetes ratio [51]. Furthermore, contrary to the control group, in the low- and high-vitamin E groups, Escherichia coli was found to be present [51].

Despite findings, with regard to the profiles of particular microorganisms in relation to diet, differing between studies, the most common result is the change in the Firmicutes/Bacteroidetes ratio. The Firmicutes/Bacteroidetes ratio, which is considered to be an indicator for gut dysbiosis, seems to increase in an unhealthy diet pattern, such as the modern industrialized diet, which includes a high amount of fat, animal protein and a lack of vitamin B12 and E (Figure 1). A higher Firmicutes/Bacteroidetes ratio is related to many inflammatory and metabolic disorders, including cardiovascular pathologies [12,13,19,117,118,119,120,121]. Although, in general, results of the intervention and observational studies confirm Bacteroidetes decrease and Firmicutes increase in obese humans [122] and animals [123], a meta-analysis performed by Sze M.C. et al. did not confirm such an association [124]. Therefore, further interventional studies across a large population are required to elucidate the relationship between the Firmicutes/Bacteroidetes ratio and obesity.