*1.1. Intestinal Microbiome*

The intestinal microbiome is the largest and most active group of microorganisms in the human body. It plays an essential role in health and disease, but due to its complexity, it is challenging to elucidate the specific interactions between the bacterial species and the impact on host metabolism. The large intestine (colon) is the main place inhabited by microbiota. It is built up by several tissue types, including lumen-facing colonocytes that form the inner epithelial layer. A healthy microbiome is advantageous to the host due to its ability to digest various large molecules, like long plant-derived polysaccharides, into smaller nutrients, like short chain fatty acids (SCFA), that can be absorbed and utilized by the host. It also produces various other molecules, such as amino acids, vitamins, and neurotransmitters, that contribute to the host's health [1,2]. Over 1000 different bacterial species colonize the human gut, the vast majority of which have yet to be functionally characterized. The microbiota composition is dynamic and influenced by a variety of environmental factors such as diet, physical activity, host genetics, age, and antibiotic treatment,

**Citation:** Wronka, D.; Karlik, A.; Misiorek, J.O.; Przybyl, L. What the Gut Tells the Brain—Is There a Link between Microbiota and Huntington's Disease?. *Int. J. Mol. Sci.* **2023**, *24*, 4477. https://doi.org/ 10.3390/ijms24054477

Academic Editor: Maria Teresa Mascellino

Received: 28 January 2023 Revised: 14 February 2023 Accepted: 20 February 2023 Published: 24 February 2023

**Copyright:** © 2023 by the authors. Licensee MDPI, Basel, Switzerland. This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution (CC BY) license (https:// creativecommons.org/licenses/by/ 4.0/).

all of which contribute to the great diversity observed in healthy individuals. It is thus a challenge to accurately characterize a healthy microbiome [3]. We took a closer look at several large-scale studies that point to the genera *Bacteroides* and *Clostridium* as being the most prevalent, with *Clostridium* being less abundant than *Bacteroides* in the human intestine. Several genera, including *Bifidobacterium*, *Eubacterium*, *Lactobacillus*, *Streptococcus,* and *Escherichia,* were also present but in much lower abundance [3]. Determining a clear definition of a "healthy" microbiome is challenging, and many various factors need to be considered. The microbiome composition is dependent on a multitude of factors that may seem insignificant at first glance. In 2010, studies conducted by the MetaHIT consortium made an attempt to quantify microbiome diversity. According to the obtained results, there are 3.3 million non-redundant genes in the human gut microbiome [4], however, it had been known until early 2000s that the human genome consists of about 22,000 genes [5]. Further research confirms that the diversity of the microbiome is enormous between individuals and can differ by up to 90% in terms of microbiome localization (e.g., those found on the hands vs. those present in the gut) [6,7]. These findings drive scientists and physicians towards developing a highly personalized treatment plan. The profile and microbiota composition changes with the host's lifespan, starting from embryos which were thought to be sterile till now. The microbiota colonizes newborns' intestines, but studies have also revealed the microbiome's presence in semen, placenta, amniotic fluid, umbilical cord blood, and meconium [8]. Moreover, factors such as delivery and feeding methods are essential for microbiota composition in infants and adults. Further, when children start to ingest solid food, their intestinal microbiome becomes more diversified, and during puberty, the release of sex hormones also contributes to microbiome maturation [9]. Next, diversification of the microbiome occurs naturally with the physiological development of the organism, i.e., the increase in length and volume of the intestines provides the microbiome with appropriate niches. Numerous studies indicate that there is a correlation between aging and microbiome composition. In 2011, a pioneering study was conducted to compare the composition of the microbiome in fecal samples from people aged 64 to 102 (study group) and young adults with an average age of 36 (control group). The results showed that the "core" microbiome—defined as the specific species found in the microbiome of at least 50% of study participants—was significantly different between the groups [10,11]. So far, the main function of the intestinal microbiome has been identified as maintaining body homeostasis. Researchers emphasize that despite the fact that technological progress is at a high level, the individual composition of the microbiome, functional characteristics, or interactions between the host and microbes have not yet been established [12]. Data collected by the Human Microbiome Project [13,14] and MetaHIT [4,15] report that 2776 species of prokaryotic microorganisms isolated from human feces have been identified (data for 2019) [16]. They have been classified into 11 different phyla, including *Proteobacteria, Firmicutes, Actinobacteria,* and *Bacteroidetes*, which make up over 90% of the microbiome, [15,17,18], while *Fusobacteria* and *Verrucomicrobia* are present in trace amounts [19]. As mentioned earlier, microbiota are essential for the proper function and homeostasis of the intestines. Interactions between gut colonocytes, immune cells, and microbiota are heavily involved in shaping the immune response throughout the body [20]. In support of this, gut microbiota transplants from healthy individuals have been found to alleviate symptoms and reduce inflammation in disorders like ulcerative colitis, irritable bowel syndrome (IBS), and hepatic encephalopathy [21,22].
