Gut-liver axis: may prebiotics play a role?

In the last few years, an increased number of studies have investigated the role of the gut microbiota on the healthy/unhealthy state of the host: gut microbiota alterations have been correlated with several health conditions diseases such as neurodegenerative disorders (Roy Sarkar and Banerjee 2019), obesity (Gual-Grau et al. 2022), irritable bowel disease (El-Salhy et al. 2019), and cardiovascular disease (Rahman et al. 2022). Less extreme effects of gut microbiota alterations include bloating, abdominal distension, and other symptoms often characterising irritable bowel syndrome (Ford et al. 2020). Such discomfort is due to microbial fermentation of food components that reach the far end of the small bowel and colon, namely fermentable oligosaccharides, disaccharides, monosaccharides, and polyols (Ford et al. 2020). This evidence has underlined the importance of identifying mechanisms to modulate and interfere with the microbiota composition and function in order to affect human health and disease. In this regard, controlled prebiotic administration has been identified as a promising intervention to modulate microbial composition.

In this latest issue, Silva et al. (2023) published interesting results investigating the effects of prebiotics galactooligosaccharides (GOS) and fructooligosaccharides (FOS) on metabolic dysfunction-associated steatohepatitis (MASH). In this work, mice received a traditional diet or a high-fat diet (HFD) for 18 weeks, which was supplemented or not with the combination of prebiotics. Results demonstrated that HFD leads to alteration in metabolic parameters and insulin resistance as well as alteration in liver histopathology (Silva et al. 2023). Indeed, the HFD group showed hepatocytes with macro- and microvesicular steatosis combined with increased liver lipid deposition and extensive fibrosis compared to the control group (Silva et al. 2023). Prebiotic supplementation leads to a significant improvement in hepatic architecture and a significant reduction in lipid deposition and a significant reduction of fibrosis (Silva et al. 2023). Furthermore, increased steatosis leads to a significant reduction in liver function and an increase in serum aspartate aminotransferase (AST) and alanine aminotransferase (ALT) activities (Silva et al. 2023), which are indicative in the diagnosis and evaluation of liver disease (Kim et al. 2008). Even in this case, FOS/GOS supplementation significantly reduced ALT and AST levels (Silva et al. 2023). Furthermore, authors found increased expression of lipogenic markers, sterol regulatory element binding protein-1c (SREBP-1c), acetyl-CoA carboxylase (ACC), and fatty acid synthase (FAS), which were reduced by prebiotic administration (Silva et al. 2023). Moreover, GOS/FOS supplementation resulted in increased expression of the lipolytic marker, adipose triglyceride lipase (ATGL), indicating a positive activation of the lipolytic pathway (Silva et al. 2023). Since MASH is associated with increased inflammation (Cobbina and Akhlaghi 2017), da Silva et al. evaluated inflammatory levels confirming that HFD was associated with increased levels of interleukin (IL)-6, IL-1beta, TNF-alpha, iNOS, COX2, phospho-NF-kB, and nitrotyrosine, which were reduced after prebiotic administration (Silva et al. 2023). They also discovered that GOS/FOS administration was sufficient to restore gut integrity compromised by HFD (Silva et al. 2023). Really interesting is also the effect of prebiotic administration on gut microbiota composition. Indeed, while HFD leads to an increased level of Firmicutes, prebiotic administration promotes Bacteroidetes augmentation with a significant increase of the species Bacteroides acidifaciens and Bacteroides dorei, which are both acetate-producer bacteria (Silva et al. 2023). This is an important result since acetate can regulate the central nervous system to control appetite (Frost et al. 2014). For this reason, authors investigated if changes in the arcuate nucleus could be detected. Results showed a significant reduction in POMC/GPR43 positive neurons, which were restored after prebiotic administration (Silva et al. 2023).

Even though prebiotics administration does not always change the composition and activity of the gut in a predictable manner (Bindels et al. 2015), it is an easier way to try to modulate the microbiota alongside with the overall dietary choices. Dietary sources of prebiotics include fruit and vegetables such as asparagus, leek, banana, chicory, and grains, such as oats and wheat, which are little consumed in the most diffused Western diet (Cryan et al. 2019). In this regard, many other studies corroborate the results obtained by da Silva et al., demonstrating that microbiota modulation through prebiotic intake can reduce colitis in rats due to the increase in Lactobacillus composition (Videla et al. 2001), increase anti-inflammatory cytokines (Vulevic et al. 2015) and reduce stress-induced corticosterone release combined with a significant increase in acetate and propionate production in mice (Burokas et al. 2017; Mohamed EL Kafoury et al. 2023). In conclusion, due to the great involvement of the gut microbiota in many pathologies, the use of prebiotics to modulate microbial composition could be a promising intervention to treat different aspects of many pathologies. This is eased by the possibility of introducing prebiotics through changing diet composition and increasing the consumption of foods rich in prebiotics.

Disclosure statement

The authors declare no conflicts of interest.