**HD—human studies**

Studies were also performed on a diverse group of people suffering from HD. Participants were clinically characterized using a battery of cognitive tests, and 16S RNA sequencing was performed on stool samples. The study involved healthy individuals (control group; n = 36) and carriers of the expanded mutated gene (n = 42). Nineteen of them were previously diagnosed with HD, and the rest were pre-symptomatic. The groups were matched by gender and age. Microbiome evaluation showed differences between the control group and the study group in the composition of the microbial community (beta diversity) as well as significantly lower species richness (alpha diversity). The results of the sequencing analysis show statistically significant differences at the phylum level (differences apply only to the group of men) in *Euryarchaeota*, *Firmicutes,* and *Verrucomicrobia*. Further changes were also observed at the family level, including: *Acidaminococcaceae*, *Akkermansiaceae*, *Bacteroidaceae*, *Bifidobacteriaceae*, *Christensenellaceae*, *Clostridiaceae*, *Coriobacteriaceae*, *Eggerthellaceae*, *Enterobacteriaceae*, *Erysipelotrichaceae*, *Flavobacteriaceae*, *Lachnospiraceae*, *Methanobacteriaceae*, *Peptococcaceae*, *Peptostreptococcaceae*, and *Rikenellaceae*, concerned only men. No significant changes at the phylum and family levels were observed in women. The obtained results confirmed the researchers' assumptions and showed changes in the composition of the microbiome between the test and control groups. In addition, the observations made provide evidence that the composition of the intestinal microbiome affects the cognitive abilities of patients. However, the results obtained in this study should be interpreted with caution. According to the authors, the study and control groups were too small to make adequate statistical analyses. Nevertheless, the information provided is essential for further research [95]. Another study conducted on patients suffering from HD indicates a correlation between changes in the composition of the gut microbiome and the immune response. The study included 33 HD patients and 33 healthy individuals; the groups were matched in terms of sex and age. In addition to assessing the fecal microflora in terms of microbial richness, structure, and diversity of abundance of individual taxa, IFN-γ, IL-1β, IL-2, IL-4, IL-6, IL-8, IL-10, IL-12p70, IL-13, and TNF-α concentrations in patients' plasma were measured. The results obtained in both experiments were correlated with each other to find connotations between them. It was shown that HD patients were distinguished by increased richness and altered microbiome structure. The analysis showed that the higher number of *Intestinimonas* bacteria is positively correlated with the Total Functional Capacity score (measured in HD patients to evaluate disease progression). It is also positively correlated with the level of the anti-inflammatory cytokine IL-4. The study also showed that the genus *Bilophila* is negatively correlated with pro-inflammatory IL-6 levels. In addition, negative correlations between *Oscillibacter*, *Gemmier,* and IL-6; *Clostridium XVIII*, TNF-α and IL-8; and positive correlations between *Porphyromonas* and IL-4, IL-10, and IL-13 were also noted. The results obtained in these experiments clearly indicate the relationship between the composition of the intestinal microbiome and the immune response in HD patients [96].

All results described in the paragraph are summarized in Table 1.

**Table 1.** Summarized results of microbiome studies performed in HD mouse models and HD patients. The table shows bacterial species changed in HD, ↑ signifies increase, ↓ signifies decrease. C – Class, O – Order, F – Family, G – Genus.

