**5. Microbial Signatures Associated with Cancer Treatment and Cardiac Diseases**

The most prevalent bacterial phyla in a healthy gut microbiome are *Firmicutes* and *Bacteroidetes*, followed by *Proteobacteria*, *Actinobacteria*, *Fusobacteria*, and *Verrucomicrobia* [95]. *Prevotella* spp. and *Bacteroides* spp. are the most prominent *Bacteroidetes* members, whereas *Bifidobacterium* is the most significant *Actinobacteria* representative [96]. However, gut microbial composition is dramatically altered in several cardiovascular diseases and distinct forms of cancer (Table 1). Interestingly, gut microbial alterations associated with the progression or pathogenicity of many of the cardiovascular diseases have similarly been reported in many cancer therapies, suggesting a potential link between cancer therapy-induced cardiotoxicity and gut dysbiosis. Thus, it is important to understand whether and what kind of correlations exist among cancer therapies, gut dysbiosis, and cardiovascular diseases.

**Table 1.** Some of the gut bacteria associated with cardiac diseases and cancer treatment.


Types of bacteria in cancer treatment:

Some cancer chemotherapies, radiotherapy, and immunotherapies have been reported to be affected by the gut microbiota, in terms of both their effectiveness and toxicity. Chemotherapeutic treatments used to treat cancer cause gut dysbiosis, which is followed by a decline in commensal microorganisms, such as *Bifidobacterium* and *Lactobacillus*, and an increase in opportunistic pathogens, such as *Clostridium difficile* [96]. By controlling the immune system, the intestinal microbiota can affect the therapeutic efficacy of medications for tumors. In contrast to non-responders (NR), PD-1 responders (R) with lung cancer in both Europe and the US had a higher relative abundance of *Akkermansia muciniphila* [97]. Studies also revealed a tendency toward a higher frequency of *Corynebacterium aurimucosum* and *Staphylococcus haemolyticus* in NR patients and a higher frequency of *Enterococcus hirae* in R patients [98]. According to some reports, Fluorouracil (5-FU) therapy results in dysbiosis in mice. After 5-FU administration, the abundance of *Bacteroides* and *Lactobacillus* species decreased, whereas that of *Staphylococcus* and *Clostridium* species increased [99]. Compared to controls, fecal samples from 36 juvenile leukemia patients receiving high-dose methotrexate chemotherapy and 36 healthy children showed a substantial decrease in *Bifidobacterium*, *Lactobacillus*, and *Escherichia coli* [100]. The intestinal barrier is broken and intestinal crypts undergo apoptosis as a result of radiotherapy [101]. In a small pilot study, radiotherapy plus antibiotics reduced *Firmicute* abundance and increased *Proteobacteria* abundance in three pediatric cancer patients with pelvic rhabdomyosarcoma [102].

Types of bacteria in cardiac diseases:

Recent studies have highlighted a possible contribution of the gut microbiome to CVD. CVDs is linked to a higher *Firmicutes*/*Bacteroidetes* (F/B) proportion. The phylum *Bacteroidetes* was found to be negatively associated with ischemic heart disease (IHD), and the order *Lactobacillales* was positively associated with IHD in a small case-control study (*n* = 128) [98]. Type 2 diabetes mellitus, a key CVD risk factor, has been sparsely linked to *Acidaminococcus*, *Aggregatibacter*, *Anaerostipes*, *Blautia*, *Desulfovibrio*, *Dorea*, and *Faecalibacterium* [103]. The reduced abundance of bacteria that produce short-chain fatty acids (SCFAs), such as *Roseburia*, *Faecalibacterium*, and *Eubacterium rectale*, and an increased abundance of host opportunistic pathogens, such as *Escherichia coli*, *Clostridium ramosum*, *Bacteroides caccae*, and *Eggerthella lenta* have been linked to a higher risk of CVDs [104,105]. Researchers have found that, compared to healthy controls, patients with atherosclerosis have reduced relative abundances of *Roseburia* and *Eubacterium* and greater relative abundances of *Collinsella* [106]. Intestinal mucosal barrier degradation and dysbacteriosis caused by lower cardiac output in HF are accompanied by elevated levels of pathogenic bacteria, such as *Candida*, and decreased levels of anti-inflammatory bacteria, such as *Faecalibacterium prausnitzii*. Additionally, elevated levels of some gut bacterial species, such as *Escherichia coli*, *Klebsiella pneumonia*, and *Streptococcus viridans* have been linked to heart failure [107].

Altogether, gut bacteria, unique or common to cancer treatment and cardiac diseases, offer a new avenue for research to learn more about clinical outcomes, potential treatments, and diagnosis, as well as a better understanding of the role of microbes in the development of cancer treatment-induced cardiotoxicity. Gut microbiota can be used as a biomarker to predict the effects of cancer therapy. Populations at high risk may receive more specialized treatment, depending on their microbiota compared to a generic one.
