1. Introduction

The importance of SCFAs for human health has been demonstrated in many studies. The production of these acids in sufficient quantities by the GM is essential for the health homeostasis and well-being of the host [20]. However, the production of these metabolites depends on the GM’s structure, whose function/composition is highly variable and significantly influenced by various factors, such as age, genetics, lifestyle and environment [21]. Hygiene and the use of antibiotics, together with the “Westernization” of lifestyles are associated with an imbalanced GM, or dysbiosis, which may lead to suppression of butyrate production [22,23,24]. Voluptuous habits like smoking or drinking alcohol could also drive to a reduction of butyrate production, due to a decrease of its fermenting bacteria producers in the GM [25,26]. Different dietary patterns, in particular of macronutrients and micronutrients diet composition and the nutritional sources of foods, contribute to GM remodeling. Among macronutrients, CHO play the most crucial role in shaping the bacterial community and their effects on GM have been the most described; according to their degree of polymerization (DP), they can be divided into sugars (DP 1–2), oligosaccharides (short-chain carbohydrates) (DP 3–9) and polysaccharides (DP > or = 10) and based on their capability to be enzymatically degraded in the small intestine, in digestible and non-digestible CHO [27]. It has been evidenced that simple sugars (e.g., sucrose, fructose) cause rapid GM deregulation and hence metabolic dysfunction in the host [28,29]; moreover contrary to popular belief, non-caloric artificial sweeteners (e.g., saccharin, sucralose, aspartame, cyclamate, neotame and acesulfame potassium), which are promoted as substitutes of foods and drinks rich in sugars calories, may be considered unhealthy for reporting both dysbiosis and disruption of metabolic homeostasis, such as glucose intolerance in a GM-dependent manner [30]. While, non-digestible CHO, specifically fiber and RS are beneficial for GM composition; in particular, fiber is a good source of MACs, necessary substrate for butyrate production as reported above, moreover a recent systematic review and meta-analysis found that dietary fiber beneficially modulates the metabolic outputs of the GM, likely due to cross-feeding interactions between butyrate producers and Bifidobacterium and Lactobacillus species [31]. Among macronutrients, proteins represent an essential source of daily energy for human diet. High dietary protein intake leads to a disproportionate decrease in faecal butyrate with a markedly decline in butyrate-producing Roseburia/ Eubacterium rectale group of bacteria populations [32]. Several dietary patterns, including Western, gluten-free, omnivore, vegetarian, vegan, and Mediterranean, have been studied for their ability to modulate the GM; among these a high adherence to the Mediterranean diet (MD) was associated with a beneficial microbiome-related metabolomic profile (high Prevotella and certain fiber-degrading Firmicutes profiles, high SCFAs production) [33]. The increased intestinal SCFAs level induced by MD diet is determined by high consumption of vegetables, fruits and legumes, which are rich sources of complex and insoluble fiber, the major substrates for microbial production of SCFAs. These foodstuffs are typical of vegan/vegetarian diet, in which SCFAs production is usually increased; farther, typical constituents of plant foods are polyphenols, a broad group of substances (such as catechins, flavonols, flavones, anthocyanins, phenolic acids) with well-described antioxidant properties. Behavioral factors, including timing of eating and overnight-fast duration, were also predictive of bacterial abundances. Kaczmarek and co-workers showed that SCFAs concentrations decrease over the course of the day, in particular butyrate, because the amount of Roseburia and Eubacterium, bacteria producing butyrate, decreased throughout the day [36].  In Figure 1 are represented the factors that promote/inhibit butyrate production through a positive or negative modulation of the GM.

Figure 1. Factors that promote/inhibit butyrate production through a positive or negative modulation of the gut microbiota (GM). Among negative factors, hygiene and the use of antibiotics, together with the “Westernization” of lifestyles (high consumption of fats and sugars, sedentary lifestyle) are associated with an imbalanced intestinal microbiota, or dysbiosis, which may lead to suppression of GM fermentation and butyrate production. Farther, voluptuous habits like smoking or drinking alcohol could also drive in a reduction of butyrate production, due to a decrease of its fermenting bacteria producers in the GM. Within the factors that positively affect the production of butyrate there are dietary patterns characterized by a high consumption of plant foods (Mediterranean, vegan/vegetarian diet), source of fiber, resistant starch and polyphenols, necessary substrates for butyrate production. Moreover, among positive modulator arise nutritional supplementation with prebiotics (that can serve as the substrates for bacterial fermentation in the colon to generate butyrate) and/or probiotics, live cultures of specific strains of bacteria that colonize the intestinal tract to promote generation of butyrate (food sources of probiotics are yogurt, fermented cheeses etc.).

2. Butyrate as a Regulator of Body Weight

2.1. Butyrate and Energy Expenditure

Modulating the energy intake-expenditure balance in the body is one of the best strategies for obesity therapy. Butyrate could act as a regulator of body weight: a reasonable speculation is that it acts on components of the energy balance, promoting energy expenditure and/or reducing energy intake. Butyrate supplementation was found to have multiple metabolic benefits, including prevention of high-fat diet (HFD)-induced obesity and obesity-associated disorders in the animal model [119,120,121,122,123,124]. In addition to its preventive actions in diet-induced disease models, butyrate is also effective in treating obesity through the promotion of energy expenditure and the induction of mitochondrial function: the mechanism of butyrate action for obesity is related to the activation of AMPK, increasing ATP consumption, and the induction of PGC-1α activity, the molecular mechanism by which butyrate stimulates mitochondrial function in association with up-regulated expression of genes involved in lipolysis and fatty acid β-oxidation [125,126,127]. Adipose tissue is an endocrine organ which constitutes the largest energy reservoir in the body and plays an important role in energy homeostasis. Thus, increasing fat mobilization in adipose tissue is an attractive potential strategy for the management and treatment of obesity. Butyrate-mediated regulation of thermogenesis and energy homeostasis was also demonstrated in a recent study performed in mice: it promotes thermogenesis in brown adipose tissue (BAT) through the activation of lysine specific demethylase (LSD1), a histone demethylase, important regulator of thermogenesis [128]. Farther, β-adrenergic receptors that are largely expressed in adipose tissue, play a fundamental role in lipolysis. Another speculation by which butyrate could induce fat burning is β3-adrenergic receptors activation in mice white adipose tissue, which may encourage potential anti-obesity application of butyrate in humans [129].

This entry is adapted from the peer-reviewed paper 10.3390/molecules26030682