Beneficial effects of ginger on prevention of obesity through Modulation of gut microbiota

Abstract

Background

The human gut microbiota performs a variety of essential physiological homeostasis functions, including the development of the immune system, nutrient synthesis, vitamin production, and energy metabolism. Ginger's extensive pharmacological actions include anti-inflammatory, antioxidant, hypoglycemic, and lipid-lowering effects. This study aimed to investigate the beneficial effects of ginger on the prevention of obesity through the modulation of gut microbiota.

Methods

This study was carried out as a systematic review in 2024 by searching on the reliable databases of PubMed, Web of Sciences, and Scopus using the keywords "Obesity", "Gut-Microbiota", "Ginger" and their MeSH were analyzed with no time limit. Articles published in English that specifically focused on the beneficial effects of ginger in the prevention of obesity through the modulation of gut microbiota were included. Abstracts, letters to the editor, protocols, review articles and studies were inaccessible were excluded from consideration. To assess the quality of the included studies, a tool comprising 10 items was developed.

Findings

Generally, 3192 papers were retrieved from the above-mentioned databases and nine papers were considered for the present study after reading titles and abstracts and by considering the inclusion and exclusion criteria. In all these studies, the impact of ginger on gut microbiota has been examined, with a consistent focus on its effects on obesity. Overall, the existing evidence suggests that ginger not only positively influences gut microbiota but also serves as an effective agent in the prevention and management of obesity.

Conclusion

These findings highlight the potential of ginger as a natural and effective option in obesity management programs and for improving overall health. Nonetheless, it is clear that the amount of ginger ingested may influence its effects, and more research is required to establish the proper dosage and understand the exact how ginger supplementation works.

Introduction

Obesity is a complex and chronic condition that often recurs, classified as a non-communicable disease [1–3]. It involves low-grade inflammation and various metabolic dysfunctions. This condition represents a major global health challenge for both adults and children. Obesity is characterized by an abnormal or excessive accumulation of body fat that can lead to serious health risks [3]. Since 1975, the global prevalence of obesity has nearly tripled, leading to an estimated five million deaths in 2019, largely due to associated comorbidities such as diabetes, It currently affects about 19% of women and 14% of men worldwide [3, 4].

An umbrella systematic review and meta-analysis conducted in 2024 reported an overall obesity prevalence of 10.91% among the Iranian population, including 9.93% in males, 9.67% in females, 6.51% among children and adolescents, and 17.20% in adults [5]. Obesity, is a critical risk factor for type 2 diabetes mellitus (DM), hypertension, cardiovascular morbidity, and heart failure [1, 6, 7]. Its diagnosis should involve a comprehensive assessment of health risks, including psychological and behavioral factors, rather than solely focusing on abnormal fat accumulation [8, 9]. Several modalities, including intensive behavioral and lifestyle counseling, obesity pharmacotherapy, and metabolic surgery, may aid in achieving and maintaining meaningful weight loss and reducing obesity-associated health risks [10]. Dietary patterns are closely associated with obesity, and emerging evidence suggests that gut microbiota significantly contribute to this relationship. Consequently, the hypothesis that obesity management may be achieved through the modulation of gut microbiota presents a promising avenue for developing effective therapeutic interventions [11].

The human gut microbiota (GM) is a complex community comprising approximately 100 trillion microorganisms. These microorganisms maintain a symbiotic relationship with the host and perform a variety of essential physiological homeostasis functions, including the development of the immune system, nutrient synthesis, vitamin production, and energy metabolism [12–14]. The composition of the gut microbiota is established early in life and becomes more stable in adulthood, influenced by factors such as age, ethnicity, medication use, and most importantly, diet [15]. An imbalance in intestinal microbes can disrupt the function of gut barriers and gut-associated lymphoid tissues (GALT), allowing components like lipopolysaccharides (LPS) to penetrate the intestinal wall. This can trigger the production of inflammatory cytokines, such as tumor necrosis factor, and promote insulin resistance, which may further contribute to weight gain [16–18]. Metabolites derived from the gut microbiota—mainly short-chain fatty acids (SCFAs), intermediate bile acid (BA) metabolites, amino acid-derived metabolites, and membrane-associated lipids—have properties that facilitate communication with the host's immune system. These metabolites directly affect immune cell behavior, including activation, differentiation, migration, and cytokine production. Through receptor interactions, they can enhance or suppress immune responses depending on the specific metabolite and context. This precise modulation is essential for maintaining immune system. In particular, SCFAs exert a significant impact on immune cells in the gut mucosa, influencing their activation and regulation, especially the differentiation and activation of regulatory T (Treg) cells. Current studies suggest that these metabolites could serve as beneficial agents in addressing obesity [19, 20]. Therefore, the gut microbiota plays a significant role in both the onset and management of obesity, highlighting the importance of considering these microorganisms in effective treatment strategies [21].

Ginger is the rhizome of the plant Zingiber officinale in the Zingiberaceae family, which has traditionally been used in herbal medicine duos due to its numerous health benefits, and now is widely distributed worldwide [22–25]. Ginger's extensive pharmacological actions include anti-inflammatory, antioxidant, hypoglycemic, and lipid-lowering effects [23, 24, 26]. Moreover, ginger essential oil (GEO) and citral not only modulate gut microbiota composition but also inhibit trimethylamine-N-oxide (TMAO) formation, a gut bacteria-derived metabolite linked to metabolic disorders. Additionally, GEO and citral have shown promise in reducing pro-inflammatory cytokine levels, thereby enhancing insulin sensitivity and significant anti-obesity activity [27]. Research has revealed various physiological effects of ginger and its bioactive components (such as gingerol, shogaol, and gingerone A) through in vivo supplementation studies. Of particular interest are the effects of ginger on the gastrointestinal tract and metabolic health. New studies have demonstrated that ginger exosome-like nanoparticles (ELNs) can alter the gut microbiome, specifically through metabolite interactions with beneficial bacteria such as Lactobacillus rhamnosus [26, 28, 29]. These results provide a basis for understanding the pharmacological effects of ginger and suggest a potential link between ginger consumption, changes in gut microbiota structure, and its effects on metabolic disorders such as hyperlipidemia and obesity. This emerging area of research offers new insights into the mechanisms by which ginger may influence metabolic health through its interactions with the gut microbiome [25, 27]. This review study is the first to examine the impact of ginger on gut microbiota modulation as a novel strategy for obesity prevention. While previous studies have focused on the individual effects of ginger or gut microbiota, this research specifically addresses the relationship between the two and their role in improving metabolic health.

The objectives of this study are as follows: collecting and analyzing existing evidence regarding the effects of ginger on the composition of the gut microbiota and exploring how these microbiome changes could play a role in preventing obesity and improving body metabolism. Additionally, this study will focus on examining the effects of ginger on reducing intestinal inflammation, which is directly associated with obesity and metabolic disorders. Ultimately, the findings of this study will assist researchers, physicians, and healthcare professionals who are seeking to develop innovative therapeutic strategies for managing obesity.

Methods

Study design

This research was conducted as a systematic review in 2024 by conducting a search in databases PubMed, Scopus and Web of Science using the following keywords: (1)‘’Obesity’’ OR ‘’Overweight’’ OR ‘’ Overnutrition’’ (2)’’Gut-Microbiota’’ OR ‘’ Gastrointestinal Microbiomes’’ OR ‘’ Gut Microflora’’ (3)’’Ginger’’ OR ‘’ Zingiberales’’ OR ‘’ Ginger rhizome’’.

The search strategy was by composition keywords. To search for relevant articles, keywords, synonyms and their combination with OR and AND operators were used to increase search sensitivity. The search strategy for the PubMed database is as follows: ((((((((obesity) OR (overweight)) OR (Overnutrition)) AND (Gut-Microbiota)) OR (Gastrointestinal Microbiomes)) OR (Gut Microflora)) AND (Ginger)) OR (Zingiberales)) OR (ginger rhizome).

Eligibility criteria

The inclusion criteria for this analysis consisted of articles published in English that specifically focused on the beneficial effects of ginger in the prevention of obesity through the modulation of gut microbiota. Abstracts, letters to the editor, protocols, Review articles and studies were inaccessible were excluded from consideration.

Quality assessment of methodology of the studies

This systematic review adhered to the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) guidelines to ensure a thorough and transparent reporting of the evidence gathered from the included studies [30]. Additionally, the accuracy of the search results was confirmed through cross-referencing the cited articles. To assess the quality of the included studies, a tool comprising 10 items (Table 1) was developed based on information from two previously reviewed studies. Each item in this assessment received a score of either 0 or 1.

Table 1.

Serious health risks of obesity

Obesity side effects	Definition	References
Type 2 diabetes mellitus	Characterized by insulin resistance and insufficient insulin secretion	[39]
Cardiovascular disease	A complex, multifactorial condition characterized by excess body fat accumulation	[40]
Chronic kidney disease	A decline in glomerular filtration rate (GFR) to < 15 mL/min/1.73 m2 or the presence of kidney damage persisting for at least three months	[41]
Metabolic syndrome	A cluster of metabolic dysregulations including insulin resistance, atherogenic dyslipidemia, central obesity, and hypertension	[42]
Polyneuropathy	A disease of the peripheral nervous system that usually results in distally emphasized, often symmetrical sensory and motor stimulation and deficits	[43]

Data extraction and synthesis

Following a comprehensive search across various databases, all identified articles were imported into EndNote software, where duplicates were eliminated. The remaining studies were then independently evaluated by two researchers with relevant expertise. At this stage, the PRISMA guidelines were employed to finalize the selection of articles. Initially, titles and abstracts were screened to identify studies that met the inclusion and exclusion criteria. Subsequently, full-text articles of the selected studies were meticulously reviewed to determine eligibility. In cases where the two researchers disagreed on the selection, a third researcher was consulted to resolve any discrepancies.

Results

A total of 4,893 records were initially retrieved through a systematic search in three major databases: PubMed, Web of Science, and Scopus. After removing 1,701 duplicates using EndNote software, 3,192 unique studies remained for title and abstract screening. Based on the exclusion criteria, 1,534 review articles, 646 unrelated by title or abstract, 976 irrelevant to the research objective, and 24 low-quality studies were excluded. Ultimately, 12 full-text articles were reviewed, and 9 were selected for final analysis based on the predefined inclusion and exclusion criteria (Fig. 1). No additional studies were identified through reference list screening.

Fig. 1.

Article selection chart based on PRISMA flowchart

The flowchart of the study selection process is illustrated in Fig. 1 according to PRISMA guidelines. Characteristics of the selected articles, including study design, geographic location, and methodology, are summarized in Table 2.

Table 2.

The tool used for measuring the quality of studies

Quality evaluation criteria	Score
1) The study objectives have been clearly stated	1
2) The type of ginger intervention has been clearly specified	1
3) The properties and active compounds of ginger have been clearly outline	1
4)) The data collection method has been clearly described	1
5) The study population has been clearly defined	1
6) The intervention has been clearly explained	1
7) The impact of ginger on gut microbiota has been reviewed	1
8)) The study design has been clearly elucidated	1
9) The study setting has been clearly identified	1
10) The study limitations have been fully reported	1
Maximum points	10

Geographically, the majority of the included studies (6 out of 9) were conducted in China, indicating a regional concentration of research on this topic. The remaining studies were conducted in the USA, Australia, and Japan. Regarding study design, seven (77%) were preclinical in vivo animal experiments, one (11%) was a double-blind, placebo-controlled randomized clinical trial, and one (11%) was an in vitro experimental simulation study.

All selected studies focused on the impact of ginger on gut microbiota composition in the context of obesity prevention or management. Despite variations in dosage, duration of intervention, and analytical methods, the findings were largely consistent. Ginger was shown to modify the Firmicutes/Bacteroidetes ratio, increase beneficial bacteria such as Lactobacillus and Akkermansia, and decrease LPS-producing bacteria—changes associated with reduced systemic inflammation and improved insulin sensitivity.

Specifically, the in vivo studies reported significant reductions in body weight, triglycerides, LDL cholesterol, and inflammatory markers such as TNF-α and IL-6 following ginger supplementation. The clinical trial observed improvements in gastrointestinal symptoms, reduced bloating, and an increase in beneficial microbiota populations. The in vitro study demonstrated ginger’s inhibitory effects on pathogenic bacteria and its support of probiotic fermentation processes.

The methodological quality of the included articles was assessed using a 10-item evaluation checklist (Table 3). Three studies received a score of 6 (33%), three scored 7 (33%), and the remaining articles received scores of 8, 9, and 10 (11% each), indicating moderate to high overall study quality.

Table 3.

Characteristics of the selected studies

Ref	Author name	Country of study	Year of study	Study type	Method	Result
[31]	Wang	China	2019	Preclinical in vivo experimental study	HFD-G group (n = 12): 500 mg/kg/day dried ginger powder- oral administration for 16 weeks	In this study, the results indicate that supplementation with ginger significantly reduces body weight, hepatic steatosis, and low-grade inflammation in mice fed a high-fat diet. Furthermore, ginger leads to alterations in the gut microbiota composition and increases beneficial bacterial species such as Bifidobacterium and short-chain fatty acid (SCFA)-producing bacteria
[38]	Panyod	USA	2023	Preclinical in vivo experimental study	125 mg/kg bw/day GEO—oral administration for 3 weeks	Healthy dietary interventions significantly reversed the progression of non-alcoholic steatohepatitis (NASH). Following 12 weeks of a harmful diet, the mice underwent healthy dietary interventions that resulted in reduced obesity, improved lipid profiles, and restoration of gut microbiota composition and function. Additionally, supplementation with ginger essential oil (GEO) and the drug obeticholic acid (OCA) synergistically contributed to the reduction of pro-inflammatory cytokines and mediated inflammatory signaling pathways
[33]	Crichton	Australia	2023	Double-blind placebo-randomized controlled trial	Intervention group: 84 mg active ingredients (64 mg gingerols, 20 mg shogaols)	In this study, the consumption of ginger root powder (Zingiber officinale) was administered for 14 days to 51 healthy participants. The results indicated a significant increase in the relative abundance of the Actinobacteria phylum following ginger supplementation (P = 0.033). Additionally, ginger led to an increase in the abundance of the genera Parabacteroides, Bacillus, and Ruminococcaceae incertae sedis, while the abundance of the genus Blautia decreased (P < 0.05). Furthermore, a significant improvement in dyspeptic symptoms was observed with ginger use (P = 0.015), whereas no significant changes were recorded in alpha and beta diversity, gut function, or other secondary outcomes
					- 4 capsules/day for 2 weeks
[35]	Alhamoud	China	2023	Preclinical in vivo experimental study	HG group (n = 10): HFD + 6G (50 mg/kg)	The effects of 6-gingerol (6G) on gut microbiota changes and serum metabolites were examined in obese mice fed a high-fat diet. The results indicated that 6G significantly altered the composition of the gut microbiota, leading to an increase in the abundance of weight-reducing genera such as Muribaculaceae, Alloprevotella, and Akkermansia, while decreasing the abundance of obesity-related bacteria like Lachnospiraceae and Lactobacillus reuteri. Additionally, 6G induced significant changes in serum metabolites associated with fat metabolism, revealing a strong correlation between alterations in gut microbiota and serum fat metabolites
					- Gavage administration for 16 weeks
[36]	Li	China	2022	Preclinical in vivo experimental study	HFD + 0.2% (wt/wt) zingerone	The study found that supplementation with zingerone significantly reduced final body weight, liver weight, and epididymal white adipose tissue weight in high-fat diet (HFD) induced obese mice, without altering food intake. Zingerone administration also improved hyperlipidemia by lowering plasma triglyceride and cholesterol levels, and It decreased lipid content In the liver. Additionally, zingerone was shown to bind to the PPARα receptor, promoting the expression of thermogenic genes such as UCP1, PGC-1α, and PRDM16 in brown and inguinal white adipose tissues. Notably, zingerone altered gut microbiota composition, reducing the Firmicutes to Bacteroidetes ratio and increasing the abundance of Akkermansia_mucinphila
					Dietary supplementation for 16 weeks
[37]	Wang	China	2022	Preclinical in vivo experimental study	HFD + MGO:	The study investigates the effects of Bentong turmeric (BGO) as a dietary supplement for improving non-alcoholic fatty liver disease (NAFLD). Over 14 weeks, BGO significantly reduced diet-induced obesity and serum cholesterol levels from 4.76 ± 0.30 to 3.54 ± 0.49 mmol/L. Liver fat scores returned to normal levels (1.6 ± 0.55), Indicating improved liver function. BGO demonstrated cholesterol-lowering effects and enhanced fat metabolism, reducing fat accumulation in the liver. BGO positively influenced gut microbiota by decreasing specific bacterial groups like Lachnospiraceae_NK4A136 and Fournierella, which may correlate with improved metabolic status and liver health
					1. low dose BGO (20 mg/kg) group
					2
					Moderate dose (65 mg/kg) group
					3. High dose (130 mg/kg) griup
					- Gavage of BGO, once a day for 14 consecutive weeks
[26]	Wu	China	2023	Preclinical in vivo experimental study	Model group (n = 8)	In this study, the effects of ginger polysaccharides (GPS) on hyperlipidemic rats were investigated. The results showed that the consumption of GPS significantly mitigated the adverse effects of a high-fat diet (HFD). Specifically, improvements were observed in blood lipid levels, serum inflammatory markers (such as TNF-a and IL-6), and antioxidant capacity (including the activities of superoxide dismutase and glutathione peroxidase). Additionally, 16S rDNA gene sequencing of fecal samples indicated that GPS increased the growth of the beneficial bacterium Akkermansia muciniphila and decreased the ratio of Firmicutes to Bacteroidetes. These changes in gut microbiome structure appear to help prevent diet-induced metabolic diseases
					GPS groups (n = 7):
					1. low dose (50 mg/kg) group
					2. mid dose (100 mg/kg) group
					3. high dose (200 mg/kg) group
					- intragastric administration (10 ml/kg) for 8 weeks
[34]	Nishiyama	Japan	2020	Preclinical in vivo experimental study	BTS group: 5% BTS	Ginger has been Identified as one of the components of Bofutsushosan (BTS). This study indicates that BTS may have positive effects on the gut microbiome and contribute to weight reduction. Specifically, a significant increase in the population of *Akkermansia muciniphila*, recognized as an anti-obesity microbe, was observed in the group of mice fed with BTS. This increase could help Improve metabolic activities and reduce obesity
					- Dietary administration for 4 weeks
[32]	Wang	China	2020	In vitro experimental simulation study	0.5 g of dried ginger extract (GE)	This study Investigated the effects of ginger extract on polyphenol profiles and Its impact on gut microbiota by simulating digestion and fermentation in vitro. The results showed that after simulated digestion, 85% of the polyphenols were still detectable, with the main polyphenol constituents identified as 6-, 8-, and 10-gingerols and 6-shogaol. After fermentation, changes in microbial populations were measured using 16S rRNA gene sequencing. The digested ginger extract (GE) significantly modulated the fecal microbiota structure and promoted the growth of beneficial bacteria such as Bifidobacterium and Enterococcus. Additionally, incubation with GE elevated the levels of short-chain fatty acids (SCFAs) while decreasing the pH. Notably, 6-gingerol was found to significantly increase the abundance of Bifidobacterium

Collectively, the existing evidence suggests that ginger may serve as a natural, effective, and safe strategy for obesity prevention and management by modulating the gut microbiota. Further high-quality clinical trials are needed to deepen our understanding of the molecular mechanisms involved and to translate these findings into clinical practice (Table 4).

Table 4.

Quality score of the 9 adopted articles

Quality evaluation criteria	[26]	[34]	[32]	[35]	[36]	[37]	[33]	[38]	[31]
The study objectives have been clearly stated	1	1	1	1	1	1	1	1	1
The type of ginger intervention has been clearly specified	1	0	1	1	1	1	1	1	1
The properties and active compounds of ginger have been clearly outline	0	0	1	1	1	0	0	0	1
The data collection method has been clearly described	1	1	1	1	1	1	1	1	1
The study population has been clearly defined	1	1	0	1	1	1	1	1	1
The intervention has been clearly explained	1	0	1	1	1	1	1	1	1
The impact of ginger on gut microbiota has been reviewed	1	1	1	1	1	1	1	1	1
The study design has been clearly elucidated	0	1	0	0	0	1	1	1	1
The study setting has been clearly identified	0	0	0	0	0	0	1	1	1
The study limitations have been fully reported	0	1	0	0	0	0	0	1	1
Total scores	6	6	6	7	7	7	8	9	10

Discussion

Obesity is one of the major public health challenges worldwide, influenced by a complex interplay of genetic, behavioral, environmental, and microbial factors. In recent years, the gut microbiota has emerged as a key player in regulating energy metabolism, appetite, and fat storage.

This study aimed to assess the beneficial effects of ginger on the prevention of obesity through the modulation of gut microbiota. The review of available studies indicates that utilizing ginger demonstrates positive effects on obesity prevention by influencing gut microbiota composition. In all studies examined, ginger consumption was associated with improvements in obesity-related outcomes and consistently reported positive effects.

Experimental and clinical evidence indicates that ginger consumption leads to a relative increase in beneficial bacteria such as Lactobacillus, Bifidobacterium, and akkermansia muciniphila, while reducing pro-inflammatory and obesity-associated microbes, including certain firm cutes species and lipopolysaccharide (LPS)-producing bacteria. These microbial shifts may contribute to improved intestinal permeability, reduced systemic inflammation, and enhanced insulin sensitivity all of which play critical roles in the pathogenesis of obesity. [31]

"The reviewed studies exhibited substantial heterogeneity in ginger dosage (ranging from 20 mg/day to 500 mg/day) and administration forms (such as powder, extract, or capsules). This variation makes it challenging to define an optimal dose or formulation for clinical application. Future research should establish standardized dosing regimens and supplementation protocols to more effectively assess ginger’s role in regulating gut microbiota and preventing obesity.

Studies such as those conducted by Zhang et al. (2019) and Wang et al. (2021) have demonstrated that ginger supplementation in animal models of obesity not only helps restore gut microbiota balance but is also associated with reductions in body weight, visceral fat, and inflammatory cytokine levels. The proposed mechanisms underlying these effects include inhibition of inflammatory pathways such as NF-κB, activation of the AMPK signaling pathway, and modulation of bile acids and short-chain fatty acids (SCFAs), all of which contribute to improved energy metabolism and glucose homeostasis.

Furthermore, bioactive compounds in ginger, such as gingerols and shogaols, possess antioxidant and anti-inflammatory properties along with selective antimicrobial activity, which can beneficially influence the gut microbial ecosystem. These attributes position ginger as a functional and natural therapeutic agent with promising potential for use in dietary strategies aimed at obesity management. [21, 32]

In a study Megan Crichton et al. investigate the effects of ginger powder supplementation on the gut microbiome and related outcomes in healthy adults were investigated. In a randomized clinical trial, 51 participants were divided into two groups: one receiving ginger (1.2 g per day) and the other receiving a placebo. The results indicated that ginger consumption led to an increase in the abundance of the phylum Actinobacteria and changes in the abundance of certain bacteria such as Parabacteroides and Bacillus, while symptoms of dyspepsia improved. However, no significant differences were observed in microbial diversity, gut function, or quality of life between the two groups. [33]

This article is important because it systematically reviews how ginger can help prevent obesity by affecting gut microbiota. It highlights the potential benefits of ginger for weight management based on credible and recent research. The article explains how ginger’s anti-inflammatory properties can help restore a healthy microbial balance in the gut, which may be beneficial in preventing obesity.

However, there are some significant limitations. For instance, the review mainly includes studies published in English, which might overlook valuable research published in other languages. Moreover, the absence of human clinical trials means that much of the evidence comes from animal studies or laboratory models. These limitations indicate a need for more comprehensive research to enhance our understanding of how ginger influences obesity and gut health.

Conclusion

This review highlights the potential role of ginger in obesity prevention through modulation of gut microbiota. Evidence suggests that bioactive compounds in ginger support microbial balance, potentially reducing obesity risk. However, the effectiveness of ginger appears to depend on dosage, and further research is needed to determine optimal intake levels and clarify the underlying mechanisms of action.

Recommendations: Based on the findings of this review, Future research should focus on clinical trials to confirm ginger’s role in obesity prevention, standardize effective dosages, and clarify its mechanisms through gut microbiota. Long-term studies, diverse populations, and advanced microbiome analysis are also recommended.

Author contributions

N.GH. wrote the protocol, helped with the search strategy, and wrote the article's first draft. A.R.K. took part in authoring the article's first draft, revising it, and managing the search strategy. E.G. and SH.SH.A. took involved in the management of the study selection, data extraction, and article quality evaluation. M.R.M.H. and M.D. wrote the study protocol, helped with study design, and revised the article's first draft critically for important intellectual content. All authors reviewed the manuscript.

Funding

There is no funding source.

Data availability

The article and its supplementary files contain the datasets that this work uses to support its conclusions.

Declarations

Conflict of interests

The authors declare that they have no conflict of interest.

Consent for publication

Not Applicable.

Ethics approval

Not Applicable.