The major pathogenic component that contributes to AS is lipid deposition. Oxidized low-density lipoprotein (ox-LDL) may carry endogenous cholesterol and modulate cholesterol expression in surrounding tissues (Groenen et al., 2021). Macrophages, which are the body’s main phagocytes, may absorb and breakdown Low density lipoprotein (LDL) and ox-LDL (Khoury et al., 2021). When macrophages phagocytose too much lipid and reach their maximal dynamic equilibrium, a mass of macrophage-derived foam cells gather in the injured arteries (Feng et al., 2021). Although AS starts in cholesterol plaques in the artery’s intima, it causes both local and systemic inflammation of both the adaptive and innate immune systems (Montarello et al., 2022). Chronic inflammatory response is thought to occur in three stages of the AS pathological process: early (lipid streak stage), advanced (fibrous plaque, atheromatous plaque formation), and late (fibrous plaque, atheromatous plaque formation; unstable plaque, plaque rupture, and thrombosis) stage (Jing et al., 2022). Ox-LDL and cytokines act on endothelial cells in the early stages of AS, causing them to release vascular cell adhesion molecules (VCAMs), selectin, and other adhesion molecules. Monocytes-macrophages, vascular smooth muscle cells (VSMCs), neutrophil cells, T lymphocytes, and B lymphocytes are among the cytokines and immune cells involved. These cells and cytokines engage with receptors on the cell membrane’s surface, which subsequently activate a number of linked signaling pathways through transmembrane signaling, inducing the production of target genes (Moriya, 2019; Roy et al., 2022). As a result, it’s critical to investigate the signaling route linked to inflammation and develop an effective therapeutic plan based on this target (Figures 1, 2).

Inflammation is largely to blame for the higher risk of CVD patients, according to decades of preclinical research. The CANTOS (Canakinumab Anti-inflammatory Thrombosis Outcome Study), which is reported in 2017, is the most important of the IL (interleukin)-1β trials. IL-1β has been linked to atherogenesis in experimental studies for decades. CANTOS find that inhibiting IL-1β decrease recurrent significant adverse cardiovascular events in CAD patients with well-controlled LDL levels, irrespective of cholesterol reduction (Ridker et al., 2017). This groundbreaking study shows that inhibiting the IL-1β/ IL-6 signaling cascade can reduce cardiovascular risk without reducing cholesterol levels, but at the cost of an increased risk of severe illness. CANTOS took inflammatory therapy in AS from a scientific hypothesis to a practical reality.

Following the success of CANTOS, many techniques for interfering with IL-1β or its production have evolved, including inflammasome inhibition. Further to that, the Colchicine Cardiovascular Outcomes Trial (COLCOT) and Low-Dose Colchicine 2 trial (LoDoCo2) demonstrate that treatment with colchicine, an anti-inflammation medication that targets multiple inflammatory pathways, reduces cardiac events in patients with atherosclerotic CVD (Tardif et al., 2019; Nidorf et al., 2020). In patients with recent or momentarily remote acute coronary syndromes (ACS), all of these investigations have shown therapeutic benefit.

Meanwhile, some potential research areas are now under active development but have not yet entered the clinical trial phase. Tocilizumab, a humanized monoclonal antibody targeting the IL-6 receptor, has already been evaluated in patients with ACS. The tocilizumab group has a higher myocardial salvage index than the placebo group, while the placebo group has a lower C-reactive protein (CRP; Kleveland et al., 2016; Broch et al., 2021). In the Cardiovascular Inflammation Reduction trial (CIRT), 4,786 individuals with past ACS and either type 2 diabetes mellitus or metabolic syndrome are randomized to low-dose methotrexate 15 to 20 mg weekly or placebo. Participants in the methotrexate group have lower high sensitivity CRP levels to begin with, and methotrexate have no effect on decreasing IL-1β, IL-6, or high sensitivity CRP levels (Ridker et al., 2019).

As a result, targeting inflammatory pathways might be a potential new method to prevent and cure AS (Kong et al., 2022). Inhibition of the immune response weakens the host’s defenses, making patients more vulnerable to infection. Hence, reducing chronic inflammation in atherosclerotic CVD is a goal. Finding a strategy to do so without affecting the immune system is critical.

The GM is a collection of microorganisms such as viruses, archaea, fungus, and bacteria that make up the gut’s most prevalent components. The microbiota is most commonly found in the gastrointestinal tract, particularly in the ascending colon, which is largely anaerobic and has a nutrient-rich environment that is conducive to microbe proliferation (Shanahan et al., 2021). The infant’s GM appears to be unstable and lacking in variety, as indicated by the technique of delivery. According to Watson et al., a cesarean section is used to deliver 64–82% of babies infected with methicillin-resistant Phylum Staphylococcus, genus Staphylococcus aureus (James et al., 2008). Babies born through cesarean section may be more vulnerable to pathogen infections. In addition, analogous to human skin, the GM of a baby delivered via cesarean section is changed and dominated by Phylum Streptococcus, Phylum Corynebacterium, and Phylum Propionibacterium (Rautava, 2017). The intestinal microbiota evolves until around the age of three, when it becomes a varied, complicated, and steady collection with 60–70% resemblance to the adult GM, influenced by the environment surrounding the baby (Kashtanova et al., 2016). Some elements can impact the microbiota throughout development, such as food (i.e., breast milk or formula feeding) and antibiotic usage, which is frequently linked to disturbance of the newborn GM. Several studies have discovered that the GM of infants can promote long-term health and that human GM at an early age is linked to certain adult health issues (Milani et al., 2017; Butel et al., 2018; Kim et al., 2019).

Nine phyla that make up the intestinal flora of adults, which are Actinobacteria, Bacteroidetes, Firmicutes, Fusobacteria, Proteobacteria, Cerrucomicrobia, Lentisphaerae, Verrucomicrobia, Euryarchaeota, and Spirochaetes (Li et al., 2014). Bacteroidetes and Firmicutes make up over 90% of the total bacterial species in a healthy bacterial ecosystem (Qin et al., 2010). Simultaneously, the F/B ratio varies greatly, which is used as a health indicator of the GM in all persons. The F/B ratio rises in obese persons (the phylum Firmicutes rises, while the phylum Bacteroidetes falls) and is linked to several CVD (Crovesy et al., 2020; Magne et al., 2020). It has been demonstrated that the microbial makeup of CAD patients’ changes, with a large rise in Firmicutes abundance and a reduction in Bacteroidetes abundance (Emoto et al., 2016; Sanchez-Rodriguez et al., 2020). The GM evolves not just in the early stages of life, but even in the elderly, with changes in bacterial diversity and shifting of dominating species (e.g., decreasing abundance of beneficial microorganisms and increasing abundance of facultative anaerobic bacteria). These alterations might be linked to the onset of AS in the elderly (Shen et al., 2021; Vourakis et al., 2021). Details are shown in Table 1.

GM, especially those belonging to the Phylum Fusobacterium, genus Clostridia and Phylum Escherichia, genus Escherichia coli, process dietary phosphatidylcholine and l-carnitine into Trimethylamine (TMA; Brown and Hazen, 2015). Through the portal circulation, TMA is transported to the liver, where it is converted to TMAO by hepatic flavin monooxygenase 3 (FMO3). The suppression of the FMO3 gene has been shown in certain studies to greatly lower the formation of TMAO (Rath et al., 2017; Luo et al., 2022). Plasma levels of TMAO are very variable both within and across individuals, making it difficult to compare research (Papandreou et al., 2020).

TMAO is different from traditional CVD risk factors in that it is produced by gut microbes. More experiments in recent years have discovered that TMAO may become a whole new marker for predicting future CVD risk, with an emphasis on the proper serum levels to diagnose CVDs (Zheng et al., 2019; Tang et al., 2021). Several innovative techniques to inhibit TMAO production and prevent AS have been discovered in recent years (Iglesias-Carres et al., 2021; Li et al., 2021). Researchers reveal in one experiment that a high-choline diet offered to mice increases intraplaque bleeding rather than changing atherosclerotic load or plaque composition, which is a very new result (Lindskog Jonsson et al., 2018). As part of immune defense, TMAO activates the heat shock protein 60, which has been demonstrated to initiate AS and to participate in foam cell formation via Toll like receptors, which are also activated by SR-A1 and CD36 in macrophages after TMAO stimulation (Febbraio et al., 2000; Wick et al., 2004, 2014; Collot-Teixeira et al., 2007). Apart from that, TMAO can activate NLRP3, which can lead to IL-1β, IL-6 and tumor necrosis factor (TNF)-α production, triggering inflammation and endothelial injury that eventually leads to AS (Wu et al., 2020). TMAO also promotes the AS development by enhancing the production of IL-1β, IL-6, TNF-α and CRP through the activation of mitogen-activated protein kinase (MAPK) and NF-kappa B (NF-κB) signaling (Seldin et al., 2016; Chen et al., 2017; Chou et al., 2019). Additionally, TMAO could reduce reverse cholesterol transport by activating the nuclear receptor Farnesoid X receptor (FXR), which in turn might reduce bile acid synthesis in the liver with the effect of accelerating AS development (Ding et al., 2018; Tan et al., 2019).

In such cases, lowering TMAO to lower the AS incidence using certain effective, safe techniques might have a big impact on public health. However, the majority of in vivo investigations are undertaken in mouse models, with only a handful of people. According to Senthong et al. (2016) and Tan et al. (2019) plasma TMAO levels are closely related to coronary atherosclerotic burden in patients with ST-segment elevation myocardial infarction (STEMI) and stable coronary artery disease (CAD). Liu et al. (2018) previously demonstrate that non-culprit plaques in CAD patients with greater TMAO levels have more susceptible features, including a thinner fibrous cap, a higher presence of thin-cap fibroatheroma and microvessels. However, A comparison of plasma TMAO levels in CAD patients and control subjects reveal no significant differences in another trial (Bordoni et al., 2020).

TMAO plays a role in the complex pathological processes of atherosclerotic lesion formation. The preliminary findings suggest that TMAO might serve as a potential target for the prevention and treatment of AS, which is conceptually novel, compared with existing treatments. The regulating of TMAO production and associated GM may be an effective strategy against AS (Zhu et al., 2020).

Certain gut microbes produce SCFAs (such as acetate, proprionate, and butyrate) by fermenting otherwise indigestible dietary fibers. It has been shown that fecal and plasma levels of SCFA are related to the presence of SCFA-producing microbiota in the gut and the consumption of dietary fibers (Calderon-Perez et al., 2020; Deehan et al., 2020; Li et al., 2020; Verhaar et al., 2020). SCFAs are absorbed and delivered through the portal circulatory system to control immunological responses and a variety of metabolic activities in the host (Wenzel et al., 2020; Yang et al., 2020). SCFAs have emerged as beneficial biological microbial products with well-known anti-atherogenic properties, such as lowering systemic inflammation, increasing endothelial cell function, and maintaining intestinal barrier integrity (Lin and Zhang, 2017).

According to a study, aortic atherosclerotic plagues are decreased by 50% when apolipoprotein E (ApoE)^−/− mice had a diet containing 1% butyrate for 10 weeks, with lower macrophage infiltration and greater collagen deposition, implying a more durable fibrous cap. These events are largely linked to a decrease in CD36 in macrophages and endothelial cells, as well as a decrease in pro-inflammatory cytokines and NF-κB activation (Aguilar et al., 2016). Butyrate also can prevent inflammation development by effecting proliferation of VSMCs (Ranganna et al., 2003; Mathew et al., 2014). Atherosclerotic GF ApoE^−/− mice were inoculated with a specified population of eight bacteria. The size of atherosclerotic plaques is decreased by 30% using that axis without changing cholesterol or TMAO levels, possibly due to SCFAs’ capacity to keep the gut healthy (Bultman, 2018; Kasahara et al., 2018). Furthermore, Bartolomaeus et al. (2019) discover that improving vascular inflammation and atherosclerotic lesion load in ApoE^−/−mice, as well as lowering blood pressure, all of which are classic plaque rupture risk factors. In addition to mitigating CVD risks, they have also been useful in mitigating diabetes, obesity, hypertension (Koh et al., 2016), etc. SCFAs improves gut barrier integrity, vascular dysfunction, hypertrophy fibrosis, and cardiac ventricular arrhythmias in ApoE^−/− mice (Du et al., 2020).

In GM-AS disease axis research, SCFA butyrate is therefore believed to act antagonistically to its counterpart secondary metabolite-TMAO. It might be a novel strategy—supplementing SCFAs to prevent AS and stabilize plaque in the event of a cardiovascular event. However, because few human studies have been completed, additional research into the role of SCFAs is still needed.

Another group of GM-produced metabolites involved in various metabolic disorders is BAs, which are stored in the gallbladder and released into the intestine to aid dietary lipid absorption and dietary fat-soluble vitamin absorption (Kuipers et al., 2014). The GM-derived enzymes usually transform primary BAs (such as deoxycholic acid, lithocholic acid hyodeoxycholic acid, and ursodeoxycholic acid) into secondary BAs. The enterohepatic system of GF mice exhibit higher levels of primary BAs, but no secondary BAs (Chiang, 2013). High fat diet (HFD)-induced gut microbiome changes are inhibited when liver BA biosynthesis is suppressed. This illustrates a metabolic link between the liver, the microbiome of the gut, and the BAs (Zheng et al., 2017). Consequently, there exists a bidirectional relationship between GM and BAs metabolism (Yan et al., 2021).

Through the BAs receptor (also known as FXR), the GM can affect lipid and cholesterol metabolism. It is vital for the absorption of dietary lipids and fat-soluble vitamins that bile acids are present (Parseus et al., 2017). Upon feeding mice a chow diet, FXR-deficient mice develop hypercholesterolemia, related to impaired high density lipoprotein (HDL) metabolism and reverse cholesterol transport (Lambert et al., 2003). Studies using FXR agonists in mice prone to AS have also demonstrated that this receptor may contribute to AS prevention, but this effect may be weight-dependent (Miyazaki-Anzai et al., 2014). Moreover, double-knockout mice for ApoE and FXR have a deteriorated plasma lipid profile and more atherosclerotic lesions compared to ApoE^−/− mice (Hanniman et al., 2005). Since FXR is expressed by aortic smooth muscle cells and endothelial cells, this leads to aortic smooth muscle cell injury (He et al., 2006; Zhang et al., 2008). Several FXR-expressing tissues may be involved in atherogenesis, and the role of microbial regulation of BAs is not fully understood. Animal studies account for the majority of current data, while human data is sparse.

BBR is a major bioactive component of Coptis chinensis and other Berberis plants, which compound with numerous pharmacological properties. In addition to improving cardiovascular hemodynamics, BBR inhibits ischemic arrhythmia, slows down AS development, and reduces hypertension (Cicero and Baggioni, 2016; Song et al., 2020). The mechanisms of BBR include platelet activation inhibited, endothelial function normalized, macrophage-derived foam cell generation suppressed, inflammation and inflammasome activation inhibited and so on (Feng et al., 2019). It also has antibacterial properties, preventing bacterial reproduction (Zhang et al., 2021).

BBR increases gut microbial community, decreases intestinal pH and exogenous antigen deposition, raises LPS-binding protein and leptin levels, decreases serum adiponectin, has lipid-lowering and hypoglycemic benefits, boosts antibiotic culture and SCFAs synthesis (Han et al., 2011; Zhang et al., 2012). BBR boosts the synthesis of SCFAs in these phyla: Roseburia, Blautia and Alistipes (Wu et al., 2020). Cohousing BBR-treated mice with HFD-fed animals inhibits atherosclerotic progression in a comparable way to non-cohoused BBR-treated mice (Shi et al., 2018). In addition to this, Wu et al. further argue that different doses of BBR demonstrate different sensitivity towards GM composition. High doses of BBR display profound GM metabolic activity through the production of SCFAs. This activity is linked to BBR-induced GM compositional shift (Zhu et al., 2018).

By restoring intestinal SCFAs levels, reducing serum LPS levels, reducing intestinal inflammation and repairing intestinal barrier integrity, BBR treatments proved effective (Zhang et al., 2019). The BBR also reverses structural and compositional changes in the GM and influences gut microbe-dependent metabolic pathways (Yang et al., 2021). These results suggest that BBR interacts with GMs in order to play a regulatory role in dysmetabolism and AS.

Anthocyanin is flavonoid polyphenols with antioxidant properties that have been associated with reduced CVD risk (Aboonabi and Singh, 2015; Garcia and Blesso, 2021). Isolated anthocyanin successfully modifies the “pro-atherogenic” GM communities by raising percentages of five genera (Bifidobacterium, Lactobacillus, Roseburia, Akkermansia and Parabacteroides; Lavefve et al., 2020; Si et al., 2021).

In addition to controlling GM, Anthocyanin enhances vascular function by increasing nitric oxide (NO) production, lowering oxidative stress, and decreasing aortic inflammation. The aortas from these animals have much less leukocyte infiltration, less plaque development and lower quantities of blood inflammatory cytokines than those in the control mice (Joo et al., 2018; Festa et al., 2021). The NF-κB inflammatory pathway, hepatic lipid metabolism and cell redox state are all under the influence of Anthocyanin at the same time (Mena et al., 2014).

In cultured macrophages and endothelial cells, Anthocyanins may also change the mRNA levels of genes associated with AS. According to a nutrigenomic research, Anthocyanins alters the expressions of 1,261 genes in the aorta, which are linked to the development and prevention of AS (Mauray et al., 2012). Protocatechuic acid is a kind of Anthocyanin metabolites that partially inhibits AS by activating the miRNA-10b-ABCA1/ABCG1-cholesterol efflux signaling pathway (Wang et al., 2012).

As a result, Anthocyanin-mediated activities significantly alleviates AS, however it is unclear how these effects would translate in “real world” with GM confounders.

PMFs, which are abundant in old citrus peels, have a wide range of biochemical functions, including antioxidant and anti-inflammatory properties (Lai et al., 2015). Aside from a well broad spectrum of their anti-AS properties, the current wave of microbial investigation has motivated scientists to explore their influence on GM balance (Yen et al., 2011).

PMFs change the GM structure to a healthy phenotype by boosting Akkermansia, Lactobacillus, Bacteroides, and Bifidobacterium genera. They increase butyrate-producing bacteria and reduces TMA-producing microorganisms, respectively. PMFs also suppress hepatic FMO3, which reduce the conversion of L-carnitine to TMAO. Apart from inhibiting the TMAO synthesis route, PMFs can also decrease the NF-κB and MAPK signaling pathways, preventing vascular inflammation (Yang et al., 2019). By lowering markers of inflammation (VCAM-1, TNF and E-selectin) and TMAO, PMFs reliably reduce L-carnitine-induced vascular inflammation. Therapy with PMFs further reduce the development of macrophage foam cells (Whitman et al., 2005; Chen et al., 2019). By using high performance liquid chromatography electrospray ionization tandem mass spectrometry, a total of 21 PMF metabolites that are discovered (Chen et al., 2020).

Quercetin is a flavonoid that may be found in a variety of foods (onions, tea, apples, etc.) and reduces platelet aggregation and thrombus development in human participants (Hubbard et al., 2004). Similarly, it benefits cholesterol metabolism, intestinal inflammation, atherosclerotic lesions and sizes of plaques, and promote gut health (Nie et al., 2019; Uyanga et al., 2021).

Quercetin has been found to have concentrated action in GM regulation, which is useful in helping mice recover their GM after receiving antibiotics and may serve as a prebiotic in the fight against gut dysbiosis (Shi et al., 2020; Zhao et al., 2021). It’s worth noting that 32 metabolic markers are discovered to drive Quercetin’s effects. The major BA production route, specifically 3, 7, 12, and 26-tetrahydroxy-5-cholestane, is one of them (C₂₇H₄₈O₄). This suggests Quercetin may increase the GM metabolite BA, correlated with circulating BAs and liver lipid and BA metabolism genes (Juarez-Fernandez et al., 2021). BAs, as aforementioned, play an important role in maintaining human metabolic processes such adipose tissue browning, insulin sensitivity and intestinal barrier integrity (Chiang and Ferrell, 2020). Additionally, intestinal Cu/Zn-superoxide dismutase, glutathione peroxidase and nutritional transporters such glucose transporter 2, peptide transporter 1 and fatty acid synthase genes have significantly higher levels of mRNA expression in the groups who received quercetin supplements (Abdel-Latif et al., 2021). With the consequent suppression of the inflammasome sensitivity and stimulation of the reticulum stress pathway, quercetin restores GM imbalance and associates with endotoxemia-mediated TLR-4 pathway stimulation (Porras et al., 2017). Quercetin and Resveratrol have positive impacts in improving the dysbiosis of the GM and obesity brought on by the HFD. They attenuate blood lipids, serum IL-6 and TNF-α and monocyte chemotactic protein (MCP)-1. Significantly limit the relative abundance of Desulfovibrionaceae, Acidaminococcaceae, Coriobacteriaceae, Bilophila, Lachnospiraceae family and result in a decrease in the F/B ratio (Zhao et al., 2017).

FA is a well-known phenolic compound that has anti-inflammatory and antioxidant properties. It helps the metabolism of lipids, diabetes and thrombosis in addition to having cardioprotective and antihypertensive effects (Neto-Neves et al., 2021). A study shows that FA can lower blood cholesterol, triglyceride and LDL levels as well as the ratio of F/B in GM composition (Ma et al., 2019). Additionally, FA lowers the expression of peroxisome proliferator-activated receptor (PPAR)-β and PPAR-γ and increases the expression of PPAR-α, a gene linked to fat metabolism. The fatty acid production and metabolism benefits from these alterations in gene expression, which also reduces fat accumulation (Yin et al., 2022).

In mice, FA can modulate the GM and inflammation and drastically reduce AS. The GM and fecal metabolites undergo noticeable structural alterations due to FA. In contrast to enhancing the Lachoiraceaea family, FA can reduce the levels of IL-1β, IL-2, IL-6, TNF-α and relative proportions of the Prevotellaceae family (Hu et al., 2022).

PJ is high in polyphenols and is renowned for its anti-AS and anti-inflammation characteristics (Danesi and Ferguson, 2017). PJ results in a significant reduction of the atherosclerotic lesion size and intima media thickness, a 20% reduction in the absorption of ox-LDL and native LDL by peritoneal macrophages (Aviram et al., 2000; Basu and Penugonda, 2009), a 27% rise in HDL content and a 12 to 18% reduction in the risk of CVD (Michicotl-Meneses et al., 2021).

In RAW264.7 macrophages, PJ stimulates cholesterol efflux from foam cells and inhibits the pathophysiology of initial atherogenesis (Zhao et al., 2016). The expression of vascular inflammation indicators, arterial endothelial nitric oxide synthase (eNOS), and levels of inflammatory cytokines [TNF-α, plasminogen activator inhibitor-1 (PAI-1), IL-17A, IL-6, IL-1β, and MCP-1] all show a considerable decline (de Nigris et al., 2007; Michicotl-Meneses et al., 2021). A PJ supplementation reduces oxidative stress in macrophages and cholesterol flux in macrophages, even also attenuates AS in mice (Kaplan et al., 2001). A dose-dependent impact of PJ and its primary polyphenols decreases TNF-α and IL-6 secretion significantly. A considerable increase in the spontaneous release of IL-10 revealed that PJ dose-dependently influences macrophages toward an anti-inflammatory M2 phenotype (Aharoni et al., 2015).

After using PJ supplements, the levels of the phenolic metabolites 3-phenylpropionic acid, catechol, hydroxytyrosol and urolithin A in the feces significantly increase (Mosele et al., 2015). PJ is reported to reverse acrolein-induced GM dysbiosis by rebalancing the F/B ratio and lowering the prevalence of Ruminococcaceae and Lachnospiraceae at the family level. In vivo and in vitro atherosclerotic models, it also preventes acrolein-induced lipid buildup, peroxidation and oxidative stress by decreasing critical lipid biosynthesis pathways (Rom et al., 2017). Furthermore, PJ with chitinglucan reduces the relative abundance of phylum Bacteroidetes, genus Alistipes and Phylum Firmicutes, genus Lactobacillus through altering their genes, also reduces hepatic lipids, inflammation and endothelial dysfunction through activating eNOS (Neyrinck et al., 2019).

RSV is a stilbenoid phenol that may be discovered in grapes, blueberries and medicinal herbs, which can reduce intestinal permeability and inflammation and enhance gut barrier (Cai et al., 2020). It is also effective anti TMAO-induced AS in a GM-dependent way and increase the abundance of genera Lactobacillus and Bifidobacterium (Chen et al., 2016).

RSV has been found by researchers to have anti-inflammatory effects and to have the ability to prevent the generation of inflammatory cytokines. This anti-inflammatory impact may be linked to the modulatory effect of microRNAs transcription with either an anti-inflammatory or a pro-inflammatory role (Dvorakova and Landa, 2017), which is predominantly mediated by the capacity to regulate NF-κβ and activator protein-1 (AP-1; Latruffe et al., 2015). In this setting, RSV has been shown to be able to reduce chronic low-grade inflammation, which is defined by the buildup of macrophages in the adipose tissue and excessive cytokine production. For instance, it reduces the release of TNF-α, IL-1β, IL-6 and IL-8 in murine adipocytes and human adipose tissue explants (Olholm et al., 2010; Yen et al., 2011). RSV may reduce inflammation linked to obesity in genetically (Gomez-Zorita et al., 2013). Even more, it can have an immediate anti-inflammatory impact in healthy persons (Ghanim et al., 2011).

RSV reduces the GM structural alterations and inflammatory markers by HFD (Man et al., 2020). Genera Bacteroides, Blautia, Lachnoclostridium, Parabacteroides and Ruminiclostridium 9 are enriched in the gut of mice treated with RSV, which is a striking modification in the makeup of the microbiota (Wang et al., 2020). The anti-inflammation benefits of RSV are substantially dependent on GM, as demonstrated by a fecal microbiota transplantation experiment (Wang et al., 2020, 2022). RSV also successfully stops the growth of Coriobacteraceae and Desulfovibrionaceae, two family that have a strong relationship with body weight that are caused by the HFD (Campbell et al., 2019).

Given atherosclerotic circumstances, TPs are reported to exhibit a wide range of biological actions, which have antioxidants and anti-inflammatory effects (Bornhoeft et al., 2012).

TPs decrease plaque/lumen area and increase Bifidobacterium colony abundances in the intestines of HFD-fed ApoE^−/− mice. Furthermore, the rise in Bifidobacterium count is approximately equal to the plaque/lumen size. This means that TPs target Bifidobacterium specifically to reduce atherosclerotic plaque (Liao et al., 2016). TPs increase SCFAs synthesis in C57BL/6 J mice with human flora (Wang et al., 2018). TPs may decrease systemic LPS levels and inflammation brought on by obesity. Toll-like receptor 4 (TLR4), as well as CD14, MyD88 and other co-receptors, are downregulated in hepatic and adipose tissues in response to the drop in the level of LPS in the blood. This further prevents NF-κB to be activated. In mice fed with HFD, TPs dramatically reduce the blood levels of TNF-α, IL-1β and IL-6. By boosting intestinal tight junction proteins, TPs also preserve the integrity of the intestinal barrier and repair gut dysbiosis in obese mice (Li et al., 2020; Ye et al., 2022).

The performance of the barrier function, particularly intestinal inflammation and the integrity of the intestinal barrier, are improved by TPs. They also reduce the phylogenetic variation and F/B ratio associated with GM dysbiosis brought on by HFD. Other fundamental bacteria are discovered to benefit from TPs include genera Akkermansia muciniphila, Alloprevotella, Bacteroides and Faecalibaculum (Zhou et al., 2021). Another study finds that TPs increase the relative abundance of phylum Firmicutes while decreasing the relative number of genera Bacteroidetes and genera Fusobacteria by 16S rRNA gene sequencing. In addition, significant correlations exist between the weight loss caused by TPs and the relative amount of the genera Acidaminococcus, Anaerobiospirillum, Anaerovibrio, Bacteroides, Blautia, Catenibactetium, Citrobacter, Clostridium, Collinsella and Escherichia (Li et al., 2020).