Microbiome Links Cigarette Smoke-Induced Chronic Obstructive Pulmonary Disease and Dietary Fiber via the Gut-Lung Axis: A Narrative Review

Abstract

Existing comprehensive management strategies for COPD effectively relieve the symptoms of patients, delay the deterioration of lung function, and prevent the progression of COPD through various means and multidisciplinary interventions. However, there has been limited progress in therapies that address the underlying causes of COPD pathogenesis. Recent studies have identified specific changes in the gut and pulmonary microbiota in response to exposure to smoke that can cause or exacerbate CS-COPD by regulating the inflammatory immune response in the lungs through the gut-lung axis. As a convenient and controllable intervention, modifying the diet to include more dietary fiber can effectively improve the prognosis of CS-COPD. Gut microbiota ferment dietary fiber to produce short-chain fatty acids, which connect the microbial communities in the lung and gut mucosa across the gut-lung axis, playing an anti-inflammatory and immunosuppressive role in the lungs. Given that the effect of dietary fiber on gut microbiota was highly similar to that of quitting smoking on gut microbiota, we assume that microbiota might be a potential therapeutic target for dietary fiber to alleviate and prevent CS-COPD. This study examines the similarities between pulmonary and gut microbiota changes in the presence of smoking and dietary fiber. It also highlights the mechanism by which SCFAs link pulmonary and gut microbiota in CS-COPD and analyzes the anti-inflammatory and immunomodulatory effects of short-chain fatty acids on CS-COPD via the gut-lung axis.

Keywords:

• CS-COPD
• gut microbiome
• lung microbiome
• dietary fiber
• SCFAs
• gut-lung axis

Introduction

Chronic obstructive pulmonary disease (COPD) is a highly pathological and potentially fatal lung disease [1], which produces irreversible airway obstruction accompanied by a progressive decline in lung function [2]. With more than 3 million deaths per year [3], COPD is the third leading cause of death worldwide [4,5]. The treatment of COPD focuses on optimizing lung function and inhibiting disease progression by utilizing drug and non-drug intervention. These interventions include long-acting beta-2 agonists (LABA), long-acting muscarinic antagonists (LAMA), inhaled corticosteroids (ICS), and macrolide antibiotics (MA). Non-drug interventions include smoking cessation, pulmonary rehabilitation, and vaccination. Existing management strategies are effective in stabilizing the progression of the disease, but they are not ideal for preventing and delaying the deterioration of lung function.

Dietary fiber includes carbohydrates with a degree of polymerization of 3 to 9 monomeric, which are neither digested nor absorbed in the small intestine [6]. Grains, legumes, vegetables, fruits, nuts, and seeds are the primary sources of dietary fiber [6]. High dietary fiber intake can reduce the incidence of COPD in current and former smokers [7,8], while decreased lung function is associated with low dietary fiber intake [9–11]. Increased dietary fiber consumption, especially in people with current or previous exposure to tobacco smoke, can help prevent cigarette smoke-induced COPD (CS-COPD) and inhibit its progression. Dietary fiber intake can also be used as a supplement to the non-drug treatment of CS-COPD. Through immunity, hypoxia, and biofilm formation, cigarette exposure can directly or indirectly enter the microbiome [12]. This leads to changes in gut and lung microbiota, which are associated with lung inflammation and immune response [13,14]. Gut microbiota may play an important role in CS-COPD [15], while microorganisms, as a powerful plastic therapeutic target, undergo bacterial remodeling under the influence of a specific diet [13]. It is now widely recognized that both cigarette smoke and fiber-deficient diets can cause dysbiosis of the gut microbiota. Short-chain fatty acids (SCFAs), a product of dietary fiber fermentation by gut microbiota, inhibit CS-COPD inflammation and immune response [16,17]. As a result, dietary fiber supplementation probably improves the prognosis of CS-COPD. It is plausible that gut microbiota may serve as a therapeutic target that links CS-COPD to dietary fiber supplementation [18]. However, no study has explored whether there is a connection or similarity between the changes in gut microbiota caused by these two intervention factors. Therefore, in this study, we analyze the effects of dietary fiber and cigarette smoke on changes in gut microbiota, in an attempt to further support the argument that gut microbiota are related to dietary fiber supplementation and CS-COPD as a potential therapeutic target. At the same time, in CS-COPD, both the gut microbiota and the lung microbiota are altered. A growing number of studies suggest a link between the lung microbiome and chronic lung disease [19], possibly influencing COPD progression by manipulating inflammatory and immune processes [20]. Similarly, nutritional changes affect the composition of lung microbiota [21]. However, there are few epidemiological studies and animal experiments on the direct or indirect effects of dietary fiber on lung microbiota through the gut-lung axis, which is a limitation of most conventional culture techniques for detecting lung microbiota [22]. Smoking is the main cause of COPD, which is in turn closely related to the abundance and diversity of gut microbiota and lung microbiota.

Smoking and gut microbiome

The microbiome is a collection of all microorganisms living in a specific location, including the gastrointestinal tract, skin, and respiratory tract [14]. There are trillions of microbes in the gut, and this "gut microbiome" constitutes a complex community that has interactions between its constituents as well as with the host. These regulatory processes are critical to the health of the host [23]. Chronic airway inflammation is one of the major drivers of the pathogenesis of COPD, and it is usually attributed to persistent acute inflammation caused by the inhalation of cigarette smoke [24]. However, the effects of cigarette smoke do not only occur in the lungs, as smoking has also now been shown to affect the distal gut microbiota [14,25]. Besides, smoking may reduce the "immune tolerance" conferred by the gut microbiota, thereby amplifying the immune response in the lungs [14]. "Healthy" gut microbiota were mainly characterized by the phyla Bacteroidetes, Firmicutes, Actinobacteria, Proteobacteria, and Verrucomicrobia [26]. The gut microbiome varies with smoking status, with current smokers generally having fewer Firmicutes and more Bacteroidetes [27]. Similarly, another study determined that the gut microbiota of healthy smokers were different from nonsmokers’. Soon after quitting smoking, the proportion of Firmicutes and Actinobacteria increase, while the quantity of Bacteroides and Proteobacteria fall [28]. The consistency of these two results indicates that smoking has a down-regulatory effect on intestinal Firmicutes, while it has an up-regulatory effect on Bacteroidetes, and this change can be reversed after the cessation of smoking. Firmicutes metabolize dietary plant-derived polysaccharides into SCFAs [29]. Not all the bacterial under Firmicutes shows consistent changes when exposed to smoke. In an epidemiological study of 248 people, the relative abundance of erysipelotrichia-catenibacterium was significantly higher in current smokers compared to people who had never smoked [30]. This bacterium is a gram-positive, non-stomatal forming, and anaerobic bacterium in the genus Firmicutes that produce SCFAs from glucose. These results also suggest that some Firmicutes may have a negative feedback effect on the reduction of Firmicutes caused by smoke. Clostridium, found to increase after exposure to smoke and belonging to the phylum Firmicutes, also produces SCFAs [31,32]. In an animal study, Lachnospiraceae, which is beneficial to the host by producing SCFAs [33], was found to have increased in the colon after 24 weeks of smoking exposure [34]. This further suggests the possibility that some Firmicutes respond negatively to changes in smoke exposure. Prevotella, which is an SCFA-beneficial bacterium in the phylum Bacteroidetes, decreases after smoking cessation, suggesting that some bacteria in Bacteroidetes may also have negative feedback changes [35,36]. In one study, the cecal microbiota of female mice were adjusted to be similar to those of male mice by conducting an ovariectomy to eliminate estrogen interference. Consistent with Allais’s conclusion, the abundance of Lachnospiraceae increased after being exposed to smoke. Besides, Alistipes, which is related to the production of SCFAs, was found to decrease with continuous exposure and was positively correlated with the bodyweight of mice [37]. Weight loss is often indicative of the advanced disease progression of COPD and indirectly suggests an association between gut microbiota and COPD. In the study of mice with CS-COPD treated by fecal microbial transplantation (FMT) and a high fiber diet (HFD), it was found that the severity of emphysema by the mean linear intercept (MRI) increased with smoke exposure, while it decreased with FMT and HFD intervention. Additionally, the family level of SCFA-producing Bacteroidaceae and Lachnospiraceae increased under the intervention of FMT and HFD [38]. Of them, the changes in Lachnospiraceae were contrary to the results of the study conducted by Allais, which may be related to different sampling sites and the influence of estrogen. In one study, Bifidobacteria decreased after smoke exposure, with the cecal levels of organic acids also falling [39]. As already mentioned, smoking can down-regulate Firmicutes and up-regulate Bacteroidetes. However, after smoking cessation, both Firmicutes and Bacteroidetes return to their original levels. Smoking is detrimental to dietary fiber-friendly SCFA-producing bacteria, but there seems to be a negative feedback compensation mechanism, that is, there is an opposite reaction to smoking within the same phylum (Figure 1).

Figure 1. Changes in the abundance of SCFA-beneficial bacteria in different phyla after smoke exposure or smoking cessation [27–31, 35, 37, 39].

Many observational studies, as well as animal experiments, have proven that smoking is a decisive factor in altering the composition of gut microbiota. Although these studies do not provide a direct link between gut microbiota and CS-COPD, it is interesting to note that some articles on the treatment of COPD by probiotics suggest that gut microbiota have a therapeutic effect on COPD. For example, gastric supplementation of Lactobacillus rhamnosus and Bifidobacterium reduced airway inflammation and alveolar loss in COPD mice [40], and an isolated strain of Parabacteroides Goldstein relieved the symptoms of CS-COPD [15]. In conclusion, SCFAs produced by gut microbiota play an important role in the pathogenesis and progression of CS-COPD. Thus, the comprehensive interventions of potentially beneficial intestinal strains combined with dietary fiber and smoking cessation may become a future direction in COPD prevention and treatment.

Smoking and lung microbiome

Lung microbiota, in contrast to fecal samples of gut microbiota, were considered sterile under the traditional culture mode of microorganisms [41,42]. Due to the application of sequencing methods, such as 16S ribosomes, RNA sequencing, and metagenomic sequencing, as well as the emergence of next-generation sequencing technologies, the way we observe the microbial community on the surface of human mucosa has changed significantly [43]. Thus, the in-depth study of lung microbiota has only begun in recent years. In the pathogenesis of COPD, reduced bacterial complexity is associated with inflammation [44], which alters the dynamics of host–microorganism interactions in the respiratory tract, subsequently leading to COPD [45]. Acute exacerbation of COPD is also associated with less diversity in lung microbiota, which results in a reduced ability to prevent the colonization of pathogenic bacteria [46,47]. Therefore, lung microbiota are an important parameter in early immune maturation [48]. Similar to the gut microbiota, lung microbiota may also have a "core microbiome", which Erb-Downward found to be mainly composed of Pseudomonas, Streptococcus, Prevotella, Fusobacterium, Haemophilus, Veillonella, and Porphyromonas [19]. Lung microbiota vary between populations and races, possibly due to environmental exposure or diet, of which smoke exposure is an important risk factor [44] since smoking affects the diversity of lung microbes [49]. In a bronchial study, Hilty et al. found low levels of different types of bacteria in the lungs of healthy smokers, with Prevotella more widespread and protein-based bacteria such as Haemophilus less common than in the COPD control group [50]. Sze et al. classified the composition of microbial communities into three different types of lung tissue by terminal restriction fragment length polymorphism analysis and sequencing. The three groups were the nonsmokers and smokers group, GOLD (Global Initiative for Chronic Obstructive Lung Disease) Stage 4 group, and cystic fibrosis (CF) positive control group. It was found that an increase of Lactobacillus in the GOLD Stage 4 group led to a rise in Firmicutes compared with other groups [51], which was consistent with the previous experimental results of Erb-Downward and Huang [19,52]. Both of these researchers believe that low diversity of lung microbiota may lead to more Proteobacteria, while a large variety of lung microbiota may result in more Firmicutes. In a cross-sectional study with a sample size of 14 people, a preliminary analysis of the microbiome and stratified lung function indicated that the microbiota diversity of moderate and severe COPD patients were very limited. Besides, by examining multiple discrete tissue sites in the lungs of six subjects removed at the time of transplantation, significant microscopic anatomical differences were found in different areas of the same lung in patients with advanced COPD [19]. At present, studies on the changes in lung microbiota in CS-COPD patients are mostly cross-sectional studies, and the results are inconsistent. This may be related to the recent emergence of new culture methods, the diversity and relative abundance of lung microbiota in different individuals, the influence of some therapeutic interventions such as bronchodilators or glucocorticoids, or variations in lung microbiota within the same lung. With advances in research, future studies should focus on large sample cohort studies, as well as longitudinal studies of the same individuals and lung tissue at the same site over time to clarify the causal association between specific lung microbiota and CS-COPD.

Microbiome, gut-lung axis, and CS-COPD

There is a relationship between the lungs and the intestine in functional structure, inflammatory response, and immunity, which is collectively referred to as the gut-lung axis [53,54]. Microorganisms play an important role in this process and affect metabolic, informational, and physiological processes. Gut microbiota are the dominant group, regulating local and systemic inflammatory responses and maintaining human immune tolerance [51,55,56]. Both directly and indirectly, gut and lung microbiota are altered in several chronic respiratory diseases, including COPD [28,51]. The regulation of COPD caused by microbiota is associated with inflammasome [16]. The NLRP3 inflammasome is thought to regulate the inflammatory cell recruitment of lung and intestinal immune response on conversion [57,58]. Also, some living bacteria or proteins from dead bacteria can colonize the lungs in cases of inflammation, microbiota disorders, or antibiotic treatments [59]. The activation of the NLRP3 inflammasome by commensal bacteria and SCFAs causes lung inflammation and immune cell activation [16], thus playing a protective role in the human body (Figure 2). Moreover, gut microbiota can secrete SCFAs, of which butyrate can reduce the lung damage caused by CS-COPD. It does this by inhibiting the Mevalonate pathway in the gut, lungs, and liver [60]. These studies suggest that the lung and the gut microbiota can influence the underlying mechanism of the cause or exacerbation of CS-COPD through the gut-lung axis, and the targeted treatment of inflammasome NLRP3 for CS-COPD may become a new therapeutic strategy in the future. The mechanism of the interaction between microbiota and inflammasome NLRP3 at both ends of the gut-lung axis has yet to be further studied. At present, it has been found that SCFAs produced by the fermentation of bacterial dietary fiber protect CS-COPD mice through NLRP3 inflammasome response [61]. Dietary fiber is currently known as a dietary intervention that links gut microbiota with CS-COPD, and high dietary fiber intake is beneficial in the treatment of CS-COPD.

Figure 2. Activation of inflammasome has different effects under various conditions. Inflammasomes, activated by commensal bacteria and/or SCFAs, maintain the intestinal epithelial barrier. When activated by inflammation, microbiota disorders or antibiotic treatments lead to systemic inflammation [16].

Dietary fiber and CS-COPD

In the ARIC cross-sectional study, Kan presented the first evidence that dietary fiber was independently associated with better lung function and reduced incidence of COPD in the U.S. [10]. On this basis, Brigham further summarized dietary patterns representatively into "Western" and "prudent" diets, by analyzing the main components of food. She found that a "Western" dietary pattern was associated with respiratory symptoms, lower lung function, and COPD in ARIC participants [11]. Similarly, Steinemann investigated the protective effect of a diet rich in fruits, vegetables, fish, and nuts on age-related chronic diseases in the SAPALDIA cohort [62]. In the National Health and Nutrition Examination Survey (NHAMES), Hanson also obtained similar results that low fiber intake was associated with reduced lung function [12]. In a case-control study with a sample of 164 people, adherence to a DASH (dietary approaches to stop hypertension) dietary pattern among patients with COPD was significantly lower than in the control group [63]. A DASH dietary approach mainly involves higher consumption of fruits, vegetables, legumes, nuts, low-fat dairy products, and whole grains along with a lower intake of red meat, processed products, salt, and sweetened beverages. All of these studies have found an association between dietary patterns of fiber intake and COPD, although they cannot determine the time frame of these associations. Besides, some of these studies did not include lung function measurements or incorrectly measured the lung function, confusing pre-bronchodilator, and post-bronchodilator readings. Therefore, a selection bias may be caused by the mistaken inclusion of asthma patients in the COPD population.

In contrast to previous studies, to minimize residual conflict by cigarette smoking, the analyses of two large U.S. prospective cohorts were stratified according to smoking status. Results indicated that a diet high in fiber, specifically cereal fiber, may reduce the risk of developing COPD [64]. In line with these studies, in two Swedish prospective cohorts, Kaluza et al. found that high consumption of fruit and vegetables was associated with reduced COPD incidence in both current and former smokers but not in people who had never smoked [8,9]. These findings both supported and expanded upon previous studies. Current epidemiological evidence indicates that high dietary fiber intake is a modifiable lifestyle factor that may decrease CS-COPD risk (Table 1). In animal studies, Jang et al. discovered that a high-fiber diet containing non-fermentable cellulose and fermentable pectin reduced the emphysema progression and inflammatory response in CS-exposed emphysema mice. Moreover, the therapeutic effects on CS-COPD observed from the diet include increasing factors that affect the diversity and metabolism of gut microbiota in CS-exposed emphysema mice [12]. High dietary fiber intake is believed to result in the production of SCFAs, which are the product of fibrous fermentation by gut microbiota. Dietary fiber is independently associated with better lung function and reduced prevalence of COPD.

Table 1. Summary of observational studies on the association between dietary fiber and COPD.

Year	Title	Reference	Study design, study population, country	n	Dietary fiber measure	Dietary fiber type	Follow-up period	Main findings
2008	Dietary Fiber, Lung Function, and Chronic Obstructive Pulmonary Disease in the Atherosclerosis Risk in Communities Study	[9]	Cross-sectional study on lung function and COPD odds, ARIC, United States	11,879	66-item semiquantitative FFQ	Meat, dairy, fruits and vegetables,refined grains, and whole grains		The first known evidence that dietary fiber is independently associated with better lung function and reduced prevalence of COPD
2018	Diet Pattern and Respiratory Morbidity in the Atherosclerosis Risk in Communities Study	[10]	Cross-sectional study on evaluating patterns of dietary intake in relation to respiratory morbidity and objective measures of lung function ,ARIC, United States	15,256	66-item semiquantitative FFQ	Meat, dairy, fruits and vegetables, refined grains, and whole grains		A "Western" dietary pattern was associated with respiratory symptoms, lower lung function, and COPD in ARIC participants.
2018	Associations between Dietary Patterns and Post-Bronchodilation Lung Function in the SAPALDIA Cohort	[52]	Cross-sectional study on investigating the associations between dietary patterns and parameters of lung function related to COPD, SAPALDIA, Switzerland	2,178	127-item FFQ	The "prudent dietary pattern" characterized by the predominant food groups vegetables, fruits, water, tea and coffee, fish, and nuts		a protective effect of a diet rich in fruits, vegetables, fish, and nuts against age-related chronic respiratory disease
2016	The Relationship between Dietary Fiber Intake and Lung Function in the National Health and Nutrition Examination Surveys	[11]	Cross-sectional study on Determining the association between fiber intake and measures of lung function,NHANES, United States	1,921	interviewer administered 24 h recalls	Fruits, vegetables, and whole grains		Low fiber intake was associated with reduced measures of lung function. A diet rich in fiber-containing foods may play a role in improving lung health
2017	Adherence to Dietary Approaches to Stop Hypertension (DASH) Dietary Pattern in Relation to Chronic Obstructive Pulmonary Disease (COPD): A Case-Control Study	[53]	Case-Control Study on investigating the association between adherence to the Dietary Approaches to Stop Hypertension (DASH) diet in patients with chronic obstructive pulmonary disease (COPD) in comparison to subjects without COPD,subjects from Alzahra University Hospital of Isfahan, Iran	164	FFQ	The DASH dietary pattern mainly focuses on higher consumption of fruits, vegetables, legumes, nuts, low-fat dairy products, and whole grains and lower consumption of red meat, processed products, salt, and sweetened beverages.		Adherence to a DASH dietary pattern among patients with COPD was significantly lower compared to the control group. Cough was significantly decreased by increments in adherence to a DASH dietary pattern.
2010	Prospective study of dietary fiber and risk of chronic obstructive pulmonary disease among US women and men	[54]	Prospective study of the association between dietary fiber intake and risk of newly diagnosed COPD , 2 large prospective US cohorts,United States	11,1580	a food frequency questionnaire designed to assess average food intake over the previous 12 months	Total fiber intakes including cereal fiber, fruit fiber, and vegetable fiber intakes	16 years	A diet high in fiber, and possibly specifically cereal fiber, may reduce risk of developing COPD.
2017	Fruit and vegetable consumption and risk of COPD:a prospective cohort study of men	[7]	prospective cohort study on association between fruit and vegetable consumption and risk of COPD by smoking status in men, a population-based prospective Cohort of Swedish Men,Sweden	44,335	96-item FFQ	Fruit items (apples and pears; fresh and frozen berries; bananas; orange and citrus fruits; and other fruits) and 13 questions about vegetables (lettuce; spinach; cabbage; cauli-flower; broccoli and Brussels sprouts; carrot; beetroot; pepper;tomatoes; onion and leek; garlic; green peas; and mixed frozen vegetables.	13.2 years	high consumption of fruits and vegetables is associated with reduced COPD incidence in both current and ex-smokers but not in never-smokers
2019	Long-term dietary fiber intake and risk of chronic obstructive pulmonary disease: a prospective cohort study of women	[8]	Prospective cohort study on association between fruit and vegetable consumption and risk of COPD by smoking status in women, a population-based prospective Cohort of Swedish Women,Sweden	35,339	67-item FFQ	Cereal, fruit, and vegetable fiber	10 years	That high fiber intake is a modifiable lifestyle factor which may decrease COPD risk Primarily in current and ex-smokers

Annotation: ARIC: Atherosclerosis Risk in Communities; SAPALDIA: Swiss Adult Air Pollution and Lung and Heart Disease in Adults; DASH dietary pattern: diet pattern mainly focuses on higher consumption of fruits, vegetables, legumes, nuts, low-fat dairy products, and whole grains and lower consumption of red meat, processed products, salt, sweetened beverages.

SCFAs and microbiome

In gut microbiota, Firmicutes, Bacteroidetes, and Actinomycetes all contain SCFA-producing bacteria [29,36,39]. The SCFAs produced by dietary fiber fermentation, particularly acetate, propionate, and butyrate [65], are all important sources of energy and also protect enteric cells. Activating inflammasome maintains the epithelial barrier and is associated with inflammation and immune cell activation in the lungs [16]. Moreover, SCFAs alleviate innate immune-mediated CS-COPD through the enteric-hepato-lung axis [66]. The addition of fermentable fiber has a positive impact on patients with chronic diseases because of its ability to promote the growth of a healthy gut microbiome and increase SCFA production by commensal bacteria [67]. Agricultural diets increase the diversity of fecal microbes and encourage the growth of "good" bacteria that produce SCFAs [29]. A high-fat and low-fiber diet in mice reduces the microbiome composition of Bacteroides and increases Firmicutes and Proteobacteria [68], a trend that is highly similar to that seen in the gut microbiota of healthy people who have quit smoking [35]. Therefore, we speculate that the effects of smoking and a low-fiber diet on gut microbiota may overlap and be largely consistent. Additionally, many patients with CS-COPD will continue to experience a deterioration in health after quitting smoking [66]. This clinical phenomenon suggests that other mechanisms lead to the onset and progression of CS-COPD in addition to the localized lung effects directly caused by smoking. The evidence mentioned above strongly suggests that smoking may alter the abundance and function of SCFA-producing bacteria and reduce the ability of gut microbiota to metabolize SCFAs in an unbalanced diet, especially a low-fiber diet. This consequently amplifies the innate pulmonary immune response mediated by the gut-liver-lung axis. In one study, Daniel et al. noticed an increase in Proteobacteria of diesel exhaust particles (DEP)-exposed mice with a high-fat diet, since a high-fat diet promotes persistent and sustained inflammation caused by bacterial alterations [69]. There is no direct evidence to prove the protective effect of dietary fiber on lung microbiota. However, according to the results of this experiment, it can be surmised that dietary fiber may alleviate smog-induced changes in lung microbiota. Nevertheless, a greater number of studies are still required to verify the effect of dietary fiber on the abundance and diversity of lung microorganisms.

Future research directions

To date, several observational studies have suggested that dietary fiber is related to better lung function and the reduced prevalence of CS-COPD. To further demonstrate the protective role of dietary fiber supplementation on CS-COPD, we still need to conduct a randomized controlled trial to investigate the role of dietary fiber intake on subjects categorized into three groups: never-smokers, smokers without COPD, and smokers with COPD. Additionally, most microbial community studies have focused on gut microbiota, and the causal relationship between specific lung microbiota and CS-COPD remains unclear. Therefore, further researches are required to clarify this, and studies on how the exposure of lung microbiota to smoke affects the host should be conducted. Moreover, there is still a limited understanding of how dietary fiber affects lung microbiota directly or indirectly through the lung-gut axis, and this should be further clarified. Besides, the mechanisms by which gut and lung microbiota treat CS-COPD through the gut-lung axis have still to be explored in depth. In recent years, much progress has been made in understanding the role of microbiota in CS-COPD and the multi-system interaction of SCFAs in the human body. Therefore, in the future, new therapeutic strategies designed around the lung and gut microbiota, such as comprehensive diet, probiotic supplements, and microbiota transplantation, will play an important role in the prevention and treatment of CS-COPD and provide new clinical ideas.

Conclusions

Ever-increasing evidence suggests that smoking has certain effects on the composition of gut and lung microbiota. The effectiveness of treatments that target gut microbiota, such as probiotic supplements and supplemental dietary fiber intake, has indirectly confirmed the association between gut microbiota and CS-COPD. Gut composition-dominated microbial metabolism inhibits lung inflammation and immune cell activation by affecting the NLRP3 inflammasome through the gut-lung axis. Epidemiological studies have shown that high dietary intake may decrease the risk of CS-COPD, promote healthy gut microbiota growth, and increase SCFA production by commensal bacteria. The effects of a low-fiber diet and smoking exposure on gut microbiota are similar and generally consistent. Overall, microbiota may be a potential internal mechanism of dietary fiber that can both prevent and alleviate CS-COPD.

Declaration of interest

No potential conflict of interest was reported by the authors.