Urbanisation and its associated factors affecting human gut microbiota: where are we heading to?

Abstract Context The continuous rise in urbanisation and its associated factors has been reflected in the structure of the human gut ecosystem. Objective The main focus of this review is to discuss and summarise the major risk factors associated with urbanisation that affect human gut microbiota thus affecting human health. Methods Multiple medical literature databases, namely PubMed, Google, Google Scholar, and Web of Science were used to find relevant materials for urbanisation and its major factors affecting human gut microbiota/microbiome. Both layman and Medical Subject Headings (MeSH) terms were used in the search. Due to the scarcity of the data, no limitation was set on the publication date. Relevant materials in the English language which include case reports, chapters of books, journal articles, online news reports and medical records were included in this review. Results Based on the data discussed in the review, it is quite clear that urbanisation and its associated factors have long-standing effects on the human gut microbiota that result in alterations of gut microbial diversity and composition. This is a matter of serious concern as chronic inflammatory diseases are on the rise in urbanised societies. Conclusion A better understanding of the factors associated with urbanisation will help us to identify and implement new biological and social approaches to prevent and treat diseases and improve health globally by deepening our understanding of these relationships and increasing studies across urbanisation gradients. HIGHLIGHTS Human gut microbiota have been linked to almost every important function, including metabolism, intestinal homeostasis, immune system, biosynthesis of vitamins, brain processes, and behaviour. However, dysbiosis i.e., alteration in the composition and diversity of gut microbiota is associated with the pathogenesis of many chronic conditions. In the 21st century, urbanisation represents a major demographic shift in developed and developing countries. During this period of urbanisation, humans have been exposed to many environmental exposures, all of which have led to the dysbiosis of human gut microbiota. The main focus of the review is to discuss and summarise the major risk factors associated with urbanisation and how it affects the diversity and composition of gut microbiota which ultimately affects human health.


Introduction
In the twenty first century, urbanisation represents a major demographic shift in developed and developing countries (Zuo et al. 2018).According to the United Nations, half of the population of the world is currently residing in urban areas and by the end of 2050, approximately 68% of the world's population is projected to be urbanised (United Nations 2018).We cannot contradict the truth that urbanisation has contributed to the development of today's society but sadly during this process of urbanisation, humans have been exposed to many changes which have created a noxious effect on our wellbeing (Mamka and Peterson 2021).Alteration in dietary habits along with the adaptation to the altered urban diet, pervasive usage of antibiotics, increased pollution, sedentary lifestyles, limited outdoor activities, and limited early-life microbial exposure, especially by children, are a few examples of major environmental exposures to which humans have adapted during the era of modernisation (Popkin 1999;Turner et al. 2004;Ojiambo et al. 2012;Tasnim et al. 2017;Zuo et al. 2018).Subsequently, all these environmental exposures during the period of urbanisation have also affected our gut microbiota (Zuo et al. 2018), a set of approximately trillions of microbes, including bacteria, fungi, viruses, and parasites that are residing in our gastrointestinal tract (Brushett et al. 2020).The gut microbiota has been linked to almost every important biological function and disruption in its quantity and composition can then lead to gut dysbiosis (Gebrayel et al. 2022).Gut dysbiosis is a serious concern as it shows its association with disease (Br€ ussow 2019).Our knowledge in understanding the association between the human gut microbiota and diseases is rapidly expanding.Yet, there is still a significant gap in our knowledge in understanding how the microbial community is evolving in response to recent urbanisation.The main focus of this review is to discuss and summarise the major risk factors associated with urbanisation and how it affects the diversity and composition of gut microbiota that affects human health.

Urbanisation-associated factors affecting gut microbiota
Replacing the traditional diet with non-traditional urban diet The dietary habits of humans have evolved drastically with rising incomes and urbanisation (Guo et al. 2019).In today's industrialised societies, an urban diet which mainly comprises red meat, processed meat, pre-packaged food, refined food, sugary items, and fatty items with reduced fibre intake, less consumption of fruits, vegetables, and whole grains (a traditional diet) has become the most accessible and common choice among people (WHO 2020).This nutrition transition across the globe during the period of urbanisation is one of the major factors that affect human health (Johnson et al. 2021) as well as altering the structure of gut microbiota (Leeming et al. 2019).A growing number of studies have supported the fact that the transition of dietary patterns globally among industrialised societies leads to an overall reduction in bacterial diversity and composition along with a decrease in some beneficial bacteria such as Lactobacillus spp., Roseburia spp., and Eubacterium rectale, and an increase in Bacteroides spp., Alistipes spp., and Bilophila spp.(Beam et al. 2021).Fast foods which are quite common and easily accessible in industrialised societies are low in dietary fibres.These dietary fibres are an excellent source of microbiotaaccessible carbohydrates (MACs), and when the gut microorganisms consume this, it provides energy to the host cells (Guan et al. 2021).Upon consumption of fast foods including saturated fats, animal proteins, and red meat, the gut microorganisms metabolise this food into metabolites such as secondary bile acids, heterocyclic amines (HCAs), and hydrogen sulphide (Huang and Liu 2019).These metabolites are detrimental to host cells and further increase the risk of cancers, such as colorectal cancer (Huang and Liu 2019).Furthermore, long-term intake of red meat and high-fat diets might increase the proportion of pathogens such as Fusobacterium nucleatum, Escherichia coli, and Bacteroides fragilis in the gut (Sears and Garrett 2014;Tilg et al. 2018;Huang and Liu 2019;Phipps et al. 2020).As the composition of these potentially pathogenic bacteria increases, it also causes an increase in their metabolites which can then lead to inflammation, barrier dysfunction, and other deleterious changes to the host cells (Sears and Garrett 2014;Tilg et al. 2018;Phipps et al. 2020).Species of Alistipes and Bilophila, that are also associated with inflammatory diseases, are found to be in increased composition in diets that are rich in fats and animal proteins (Feng et al. 2017;Singh et al. 2017;Parker et al. 2020).Apart from increasing the inflammation-causing bacteria, it also reduces beneficial bacteria, such as Akkermansia muciniphila and Lactobacillus, which are beneficial for human health (Singh et al. 2017).Human studies have shown that the urban diet causes intestinal dysbiosis that can lead to endotoxemia, mainly due to damage to intestinal permeability and barrier functions, which further supports pathogen colonisation (Martinez-Medina et al. 2014).Consumption of high dietary sugars in today's commercialised foods, which is again a favourite choice among today's kids and youngsters, leads to dysbiosis (Satokari, 2020).It causes a reduction in bacterial diversity, reduced abundance of Bacteroidetes, and an increase of Proteobacteria (Do et al. 2018).Proteobacteria are a minor part of the human gut microbiome.However, their disproportionate increase may cause non-specific inflammation (Mukhopadhya et al. 2012;Satokari 2020).More recently, a study conducted in the USA showed that switching from a high fibre diet to a low fibre, high simple-sugar diet triggered functional gastrointestinal disorders (FGIDs) related symptoms and decreased small intestinal microbial diversity while increasing small intestinal permeability (Saffouri et al. 2019).Artificial sweeteners (AS) have grown in popularity as a non-caloric sweetening agent in recent times and have been linked with harmful effects, including disrupted gut microbiota, impaired glucose homeostasis, and higher risk of obesity (Palmn€ as et al. 2014;Suez et al. 2014;Azad et al. 2016;Olivier-Van Stichelen et al. 2019;Nettleton et al. 2020;Wang et al. 2021).A recent study demonstrated the effects of AS on gut bacterial pathogenicity and gut epithelium-microbiota interactions (Shil and Chichger 2021).Their findings reveal that AS differentially increases the ability of bacteria to form a biofilm.Co-culture with human intestinal epithelial cells (Caco-2 cells) shows an increase in the ability of gut bacteria to adhere to, invade and kill the host epithelium (Shil and Chichger 2021).Food sources rich in dietary fibres (from whole grains, vegetables, fresh fruits, nuts, seeds, etc.) which are unfortunately ignored in today's urbanised world, support the overall health of the intestine by increasing the proportions of probiotic bacteria including Bifidobacterium and Lactobacillus (Huang and Liu 2019).Food that is rich in complex carbohydrates is packed with more nutrients and also causes a reduction in the pathogenic species such as Mycobacterium avium subspecies paratuberculosis and Enterobacteriaceae (Brown et al. 2012), as compared to a diet which has high proportions of proteins and fats (Brown et al. 2012).

Excessive usage of antibiotics
In today's urbanised era, the misuse and over-prescription of antibiotics have led to an increase in their consumption by 46% in the last two decades (Brown et al. 2012).Antibiotics are used extensively in agriculture, livestock, and animal husbandry to increase productivity, treat sick animals, and as growth promoters (Mann et al. 2021).This excessive usage of antibiotics has also caused detrimental effects on the gut microbial population (Zhang and Chen 2019).A growing number of studies have proved that antibiotics can cause short-term and long-term effects on gut microbial populations (Panda et al. 2014;Yang, Bajinka, et al. 2021;Yang, Sakandar, et al. 2021).Antibiotic usage has been linked to a decrease in gut microbial diversity.Following antibiotic treatment, the recovery of microbial diversity in children has been found to take about a month (Yassour et al. 2016).In adults, a combination of meropenem, gentamicin, and vancomycin increased the incidence of Enterobacteriaceae and other pathobionts while decreasing Bifidobacterium and butyrate-producing species (Palleja et al. 2018).Moreover, after the completion of antibiotics, the gut microbiota baseline composition was mostly recovered within 1.5 months, but certain common species remained undetectable (Palleja et al. 2018).More often, the routinely prescribed broad-spectrum antibiotics such as amoxicillin can lead to a reduction in some of the beneficial species such as Bacteroides spp., Bifidobacterium spp., and Lactobacillus spp., thus negatively affecting the gut microbiota taxonomic richness and diversity (Elvers et al. 2020).It is important to mention here that the antibiotic's direct toxicity can induce pathogenic bacterial overgrowth by altering digestive functions, resulting in antibiotic-associated diarrhoea (AAD) (Song et al. 2008).It has been observed that antibiotics such as clindamycin or tigecycline reduce gut bacterial diversity and make the host cell vulnerable to Clostridium difficile infection (Buffie et al. 2012;Bassis et al. 2014).Similarly, the usage of streptomycin and vancomycin has been associated with increased vulnerability to Salmonella typhimurium infections (Sekirov et al. 2008).Another damage that broad-spectrum antibiotics are causing to gut microbial communities is that they can indirectly kill the commensal or good bacteria of the gut indiscriminately (Willing et al. 2011).For example, the antimicrobial activity of vancomycin is limited to gram-positive bacteria, however, during the treatment, it was observed that gram-negative populated bacteria were also significantly reduced (Robinson and Young 2010).Antibiotic usage has been linked to a decrease in gut microbial diversity.Following antibiotic treatment, the recovery of microbial diversity in children has been found to take about a month (Yassour et al. 2016).In adults, a combination of meropenem, gentamicin, and vancomycin increased the incidence of Enterobacteriaceae and other pathobionts while decreasing Bifidobacterium and butyrate-producing species (Palleja et al. 2018).Moreover, after the completion of antibiotics, the gut microbiota baseline composition was mostly recovered within 1.5 months, but certain common species remained undetectable (Palleja et al. 2018).

Preference for caesarean delivery over vaginal delivery
In today's world, the rates of caesarean deliveries (CD) are rising at an alarming rate (World Health Organization 2021a).CD accounts for more than one-fifth (21%) of all childbirths.This figure is expected to rise further over the next decade, with nearly one-third (29%) of all births likely to be delivered via caesarean by 2030 (World Health Organization 2021a, 2021b).CD can prevent maternal and new-born death and disability (Gupta and Saini 2018), However, not all CDs performed at the moment are medically necessary (World Health Organization 2021a, 2021b).Unnecessary medical interventions can be harmful to both the mother and her child (Gupta and Saini 2018).Studies have confirmed different intestinal microbiota patterns between CD and vaginal delivery (VD) babies.Infants born through VD get their intestinal flora mainly through the mother's vaginal tract and faecal flora (Yang, Bajinka, et al. 2021;Yang, Sakandar, et al. 2021).Unfortunately, the infants that are born through caesarean do not get this direct contact (Yang, Bajinka, et al. 2021;Yang, Sakandar, et al. 2021).The gut microorganisms of VD infants contain an increase of Lactobacillus, Prevotella, or Sneathia species during the initial days, which reflects the high load of lactobacilli in the vaginal flora of their mothers (Dominguez-Bello et al. 2010).In contrast, the infants that were born through CD have depleted microbiota and delay in the colonisation of the intestinal flora such as bifidobacteria, Bacteroides, and lactobacilli (Hall et al. 1990;Adlerberth et al. 2006;Jakobsson et al. 2014), at least for the first few months after birth (Gr€ onlund et al. 1999;Jakobsson et al. 2014).Moreover, pathogens from the hospital setting, such as Enterococcus, Enterobacter, and Klebsiella have been observed in the intestines of the new-borns (Shao et al. 2019).It was observed that the gut flora of infants born with CD was quite different from the ones born through VD via microbial cultures.This difference was quite obvious when they compared the rate of colonisation of Bacteroides fragilis in the gut which was 36% in CD infants as compared to VD.This percentage was less than half when compared with VD infants in which the rate was 76% (Gr€ onlund et al. 1999).Bacteroides fragilis has been demonstrated to generate a range of bacteriocins that are useful for inhibiting closely related species (Bjerke et al. 2011).Moreover, fluctuations of Bacteroides fragilis colonisation have been linked to asthma (Vael et al. 2008) and pollen allergy (Odamaki et al. 2007).CS babies are more colonised by facultative anaerobes such as Clostridium species and a few other harmful bacteria such as Staphylococcus and Acinetobacter which are commonly found in hospitals (Dominguez-Bello et al. 2010).This also explains why CS babies are more vulnerable to certain pathogens as compared to VD infants.Studies have shown that gut bacteria have played a significant role in the development of the immune system in new-borns (Sanidad and Zeng 2020).Nevertheless, this also means that, if the colonisation of intestinal microbiota is different according to the mode of delivery, then there are possible chances that the immune system development in an infant after birth may also differ (Cardwell et al. 2008;Neu and Rushing 2011;Nunez et al. 2021).Epidemiological studies have shown that CS babies have a prediction of atopic diseases as compared to the VD babies (Bager et al. 2008;Keshet et al. 2020;Kolokotroni et al. 2012;Chen et al. 2017).For example, the data of 219 children born by VD and CD have shown that the frequency of asthma at the age of seven years was considerably greater in children born by CD than in those children who were delivered through VD (Kero et al. 2002).A similar type of study was conducted with the aim of understanding the relationship between CD and atopic diseases.After analysing the data of 2,500 infants, their findings imply that CD might be an additional risk factor for wheeze and allergy sensitivity to food allergens in children under the age of two (Negele et al. 2004).Apart from allergic diseases, the risk of other diseases, including coeliac disease (Decker et al. 2010), obesity (Pei et al. 2014;Mueller et al. 2017), type-1 diabetes (Cardwell et al. 2008;Tanoey et al. 2019), and even hypertension in young adults (Ferraro et al. 2019), has also been observed in CS-delivered subjects.The association between mode of delivery and its consequent effect on gut microbiome dysbiosis has been of interest lately.

Trend of immigration from developing countries to developed nations
Globally, immigration is transforming societies (Porter and Russell 2018).According to new data from the United Nations Department of Economic and Social Affairs, the number of international migrants has now reached 272 million, surpassing the world's population growth rate (United Nations News 2019).The process of human migration not only involves the movement of people across borders, but this movement is coupled with changes in their food patterns, lifestyle behaviours, and geographical environment (D'Alonzo and Garsman 2020).It is an established fact that intestinal microorganisms are highly adaptable to the environment (Tasnim et al. 2017).Therefore, it can be justified to link an association between the increasing trend of immigration in today's industrialised world with the gut microbiome.Unfortunately, despite having a strong reason to believe their interconnection, very few studies are available which have determined the effects of migration on human gut microbiota, as it is connected with humans in both health and disease.Human knowledge has just been initiated to analyse the effects of immigration on the gut microbiome.A study conducted in the year 2018 showed that the gut microbiota structure of Thai immigrants who migrated to the United States began to alter in just a short period of approximately six to nine months.DNA sequencing for gut microbial population identification revealed a loss in bacterial diversity along with a loss in native strains, loss of fibre degradation capability, and shifts from Prevotella dominance to Bacteroides dominance (as the urban diet has more protein contents) in Thai immigrants as compared to their native Thai residents (still living in Thailand).Moreover, the prevalence of obesity was also found to be gradually increased within just one generation of Thai immigrants (Vangay et al. 2018).A recent study conducted among United States (US) Hispanics/Latinos adults revealed that US immigration was linked with decreased gut microbiome diversity along with a reduction in gut microbiome functions and alterations in gut bacterial taxa including an increase in Acidaminococcus, decreased Roseburia, and Prevotella.However, these alterations in the gut microbiome have possibly been linked to their urban diet during the adaptation process while settling in the US (Wang et al. 2021).Moreover, changes in gut microbiome features associated with the US immigration were also linked to obesity, implying that the gut microbiome may play a role in the development of obesity among Latin American immigrants to the United States (Wang et al. 2021).Here the important point is the loss in bacterial diversity which is a serious concern, and this diversity loss can also be linked with obesity as suggested in many studies.Similarly, a study conducted on Australian Chinese immigrants (children) showed that they have an increased incidence of atopy, allergies to food, and wheezing compared to Chinese-born Chinese children (Guo et al. 2019).Interestingly, the authors also found an abundance of gramnegative bacteria in Chinese-born Chinese children as compared to the immigrants (Guo et al. 2019).Apart from bacterial diversity loss, immigration can also cause an increase in gut microbiome antibiotic resistance gene (ARG) richness.Even after half a year of their settlement in the host country, the immigrants had shown increased beta-lactam, tetracycline, vancomycin, macrolide-lincosamide-streptogramin, aminoglycoside, and multidrug ARG subtypes (Le Bastard et al. 2020).Considering the profound role of immigration on the gut microbiota in this era of industrialisation, the scientific community sees the loss of microbial species as a potential health threat, which will compromise the health of future generations.

Lifestyle: active and sedentary lifestyle
The lifestyle patterns of humans have changed drastically because of urbanisation and globalisation (Gupta and Jadon 2019).A sedentary lifestyle, which involves little or no physical activity has now become a new normal, especially among youth (Castellanos et al. 2019).Human as well as animal models have proven that physical exercise is a positive influencer on gut health (Evans et al. 2014;Lambert et al. 2015;Liu et al. 2017).The effects of a sedentary lifestyle on the human gut microbiome have not been examined directly.However, an indirect way by which one can understand the importance of being active is by analysing the effects of exercise on the gut microbiome.In humans, a study conducted on Irish rugby players showed significantly higher bacterial diversity as compared to the controls (Clarke et al. 2014).The gut microbiota of the players revealed lower abundances of Bacteroides and Lactobacillus and increased abundances of Akkermansia muciniphila along with a decrease in inflammatory cytokines and an increase in levels of anti-inflammatory cytokines (Clarke et al. 2014).Akkermansia muciniphila is a mucin-degrading bacterium (Geerlings et al. 2018) whose low abundance is found in diabetic and obese patients (Everard et al. 2013).In another study, Estaki et al. investigated the gut microbiota of 39 healthy adults with different cardiorespiratory fitness (CRF) levels.After performing high throughput sequencing for the gut microbiota analysis, they observed that CRF was associated with higher diversity of gut bacteria regardless of diet amongst physically fit participants along with an increased abundance of butyrate-producing taxa, such as Clostridiales, Roseburia, Lachnospiraceae, and Erysipelotrichaceae (Estaki et al. 2016).This further suggests that physical exercise could be employed as therapeutic support in the treatment of dysbiosis-related disorders.Similarly, athletes' guts were found to be more diversified and richer in terms of bacterial species as compared to sedentary healthy individuals' controls (Kulecka et al. 2020).Interestingly, the genus Veillonella was found to be abundant in athletes (Kulecka et al. 2020).This is consistent with a previous study that demonstrated the performance-enhancing capabilities of Veillonella atypica (Scheiman et al. 2019).A recent study conducted in less active people with Type 2 diabetes (T2D) showed that moderate-intensity exercise with longer duration increased Bifidobacterium and Escherichia genera along with an increase in Akkermansia muciniphila (Torquati et al. 2022).Even minimal physical activity as suggested by the WHO (Physical activity 2022) can be beneficial for promoting gut health (Bressa et al. 2017).Individuals who exercise regularly and eat a diet high in fibres and low in sugars have a more complex microbiota network, which can lead to a more resilient microbiota than sedentary individuals (Castellanos et al. 2019).A study conducted in Spain between females of sedentary (SED) and active (ACT) lifestyles showed that Bifidobacterium, Barnesiellaceae, Odoribacter, Paraprevotella, Turicibacter, Clostridiales, Coprococcus, Ruminococcus, and two unknown genera of Ruminococcaceae family were significantly different between ACT and SED (Bressa et al. 2017).Interestingly, the qPCR analysis revealed that the bacterial species, specifically Akkermansia muciniphila, Faecalibacterium prausnitzii, Roseburia hominis, and Bifidobacterium longum, were found to be significantly greater in ACT women in comparison with the SED women (Bressa et al. 2017).It is noteworthy to mention here that these bacterial species are known for their health-promoting effects.For example, both Roseburia hominis and Faecalibacterium prausnitzii are beneficial for human health as they produce butyrate, which improves gut health and also aids in the metabolism of lipids (Nie et al. 2021;Maioli et al. 2021).

House environment and practices
Our microbial communities are likely shaped by our surroundings, including the people whom we live and interact with (Song et al. 2013).In recent times, families have become smaller as compared to the past, which may reduce the transmission of microorganisms between siblings.
Moreover, older siblings in the family are also believed to be playing an essential part in shaping the gut microbial profiles of the younger siblings (Laursen et al. 2015).Children with older siblings have more diversified gut microorganisms and are richer especially in Firmicutes and Bacteroidota phyla as compared to those children without elder siblings (Laursen et al. 2015).These two phyla are the key players in adult microbiota.Studies have also shown that the gut microbiota in younger siblings is more colonised with Lactobacillus, Bacteroides, and reduced proportions of Clostridium, lower levels of Peptostreptococcaceae, increased levels of Bifidobacterium, and lower levels of Enterobacteriaceae (Yap et al. 2011;Penders et al. 2013;Azad et al. 2016).Another study had shown that infants without elder siblings showed lower levels of facultative anaerobes as compared to the ones who have older siblings (Adlerberth et al. 2007).The authors further suggest that it is likely that the older children are a possible source of transferring strict anaerobic bacteria to the younger ones (Adlerberth et al. 2007).However, all these effects on the gut microbiome of the younger siblings increase during the initial stages of life, when they are more in contact with their siblings (Laursen et al. 2015).Customs and traditions are also known to play their part in shaping the gut microbiota.In this context, a study was conducted to analyse the impact of the Japanese bathing cultural tradition on the gut microbiome.In Japanese culture, the purpose of bathing is somewhat more than just personal hygiene and relaxation.For them, bathing is especially performed to create family bonding, such as between parent and child, between siblings, or between close friends.As per this custom, the family members before entering the bathtub must clean themselves with soap to avoid contamination of the water in the bathtub.In this way, they don't replace the bathtub water, until the last family member has completed his/her bathing.By performing 16S gene sequencing, their findings revealed that the diversity and composition of gut microbiota isolated from stool samples were significantly similar between the family members who share this custom as compared to those family members who do not engage in this practice.The researchers concluded that this tradition of sharing the bathtub water acts as a significant environmental vehicle/factor for the transmission and exchanging of gut microorganisms between family members and close friends (Odamaki et al. 2020).This is just one example showing the effects of culture and traditions on the effect of gut microbiota.However, this science is still young, and much research is still needed.

Increased environmental pollution
It is indisputable that the increased rates of urbanisation that our world is facing since the beginning of the industrial revolution are heavily responsible for environmental pollution (Aslan et al. 2021).Limited data from a growing body of recent research have shown that pollutants from the environment have the potential to change the composition and the function of the gut microbiota in both human and animal models (Jin et al. 2015;Zhang et al. 2015;Jin et al. 2017).The association between urbanisation, environmental pollution, and gut dysbiosis is a triangular process, in which urbanisation (and its associated activities) is largely responsible for environmental pollution which in turn becomes a risk factor for urbanisation-associated gut dysbiosis.A recent study conducted among healthy adults from Southern California has shown that exposure to air pollutants was associated with alterations in gut microbiota including lesser gut bacterial diversity and numerous gut bacterial species with the exception of Bacteroides caecimuris which was increased with higher exposure to ozone (Fouladi et al. 2020).Heavy metals are well-known environmental pollutants and studies have found that toxicity due to exposure to heavy metals has been associated with gut dysbiosis.For example arsenic, a ubiquitous environmental toxicant, induced gut microbiota modification that can further lead to alterations in gut permeability (Choiniere and Wang 2016).Pesticides are another major environmental contaminant whose usage has been increasing year by year and have the potential to alter the gut microbiota and cause additional symptoms in animals due to their antimicrobial activity (Jin et al. 2017).In offspring female mice, perinatal exposure to nitenpyram caused alterations in the gut microbiota and faecal metabolites, resulting in an increase in Akkermansia and a decrease in Desulfovibrionaceae and Lactobacillus.In addition, metabolites in faeces, primarily related to purine and branched-chain amino acids (BCAA) metabolism, as well as the tricarboxylic acid (TCA) cycle, were altered, resulting in an increase in host energy consumption (Yan et al. 2020).At low dosages and with ongoing treatment in rats, permethrin (PEM), a pesticide, can lower the number of Bacteroides, Prevotella, and Porphyromonas while elevating the abundance of Enterobacteriaceae and Lactobacillus (Nasuti et al. 2014).A similar type of study was conducted in Southern China with the purpose of analysing the effects of particulate matter (PM) pollution on gut microbiota.They observed that exposure to PM2.5 and PM1 was linked to lower gut bacterial alpha diversity.Exposure to PM was also shown to be negatively linked with the gut microbial taxa Firmicutes, Proteobacteria, and Verrucomicrobia, as well as positively and negatively associated with various species from the phylum Bacteroidota (Liu et al. 2019).The air pollution caused by transportation vehicles is also another serious concern.A study was conducted in Southern California among obese and overweight adolescents on the effect of traffic-related air pollution (TRAP) on gut bacteria (Alderete et al. 2018).They found that the exposure was linked to gut microbial dysbiosis and fasting glucose levels.These findings imply that exposure to air pollution may have a deleterious influence on metabolic health via changes in the gut microbial populations.

Increased stress and depression
Increased stressors and factors like overcrowding and pollution, high crime rates, and a lack of social support all have an impact on mental health as a result of urbanisation (Srivastava 2009).Chronic stress increases the likelihood of depression which on average affects 3.8% of the world's population (World Health Organisation 2021a, 2021b).Dysbiosis of the intestinal bacteria has been found in patients with mental illnesses, including depression (Limbana et al. 2020).Studies have shown that alteration in the gut microbiome including reduced bacterial diversity has been associated with social stress (Tannock and Savage 1974;Bailey et al. 2011;Bangsgaard Bendtsen et al. 2012;Galley et al. 2014;Marin et al. 2017;Partrick et al. 2018).A study conducted on rats showed that one hour of daily stress treatment resulted in a clear differentiation in both microbial populations (microbial species and distribution) and metabolism (Xu et al. 2020).However, the differences in microbial populations were reduced three weeks after the stress was removed, but the differences in microbial metabolic profiles persisted into adulthood.Stressors are also involved in reducing the beneficial microbes.Two hours daily of social stressors caused a reduction in beneficial Lactobacillus and Parabacteroides in mice along with altering the microbiota associated with the colonic mucosa and changing the structure of gut bacterial beta diversity (Galley et al. 2014).The gastrointestinal epithelium can be compromised by disruptions to the richness and evenness of the intestinal microbiota, which can lead to bacterial translocation and a proinflammatory immune response.The permeability of the gut barrier can be increased by stress and depression.This results in a "leaky gut," which allows bacteria to enter the bloodstream and cause an inflammatory response (Madison and Kiecolt-Glaser 2019).Both depression and stress have been linked to increased inflammation (Kiecolt-Glaser et al. 2018;Glaser and Kiecolt-Glaser 2005) and gut leakiness (Glaser andKiecolt-Glaser 2005, Maes et al. 2012).The relationship between gut microbiota and stress that ultimately affects mental health is a relatively new research topic that has gained importance in recent years (Limbana et al. 2020).However, much research on humans is needed to further explain this association.

Positive effects of urbanisation on human health
It is highly important to mention here that humans along with the environment are affected in two different ways with urbanisation (Shao et al. 2022).Greater accessibility to healthcare care facilities, improved water quality, upgraded lifestyle, advances in food and nutrition, and hygienic infrastructure are all made possible because of urbanisation (Shao et al. 2022).For example, if we look at nutrition where increased consumption of fast food has negatively affected human health and gut bacteria, on the other hand advances in supplements, for example probiotics, are benefitting humans in many ways.The market for probiotics is rapidly expanding, especially in the past two decades (Paraskevakos 2022), and is becoming a prominent effective therapeutic approach by healthcare experts (Sanders et al. 2018) for regulating intestinal microbial communities and suppressing the growth of pathogens, inhibiting the colonisation of pathogenic bacteria in the intestine digestive and immune health (Hemarajata and Versalovic 2013).However, their usage is not limited to human health.They are now widely used in the field of agriculture (Porto de Souza Vandenberghe et al. 2017), aquaculture (Mart ınez Cruz et al. 2012), dermatological therapy and skincare (Al-Ghazzewi and Tester 2014), to increase growth performance, disease resistance, anti-ageing and anti-inflammation as well as a substitute for antibiotics.Similarly, where sedentary lifestyles and lack of exercise in the urban environment increases the likelihood of being overweight and obese (Silveira et al. 2022), on the other hand the global gym and health and fitness clubs market has also grown significantly in recent times (Ramos 2021).Urban population growth has resulted in a lifestyle change.The pace of life has greatly increased, and stress levels are growing.Because of the multiple sources of awareness available in recent times for staying fit, healthy, and in shape, the urban population are joining gyms and health clubs in their leisure time which has resulted in a positive effect on overall well-being (Warburton et al. 2006), along with benefits to the gut microbiota which are already discussed above.In urban cities, it is faster and more affordable to build, maintain, and run environmentally friendly infrastructure and public services like piped water, sanitation, and waste management.More individuals now have easy access to affordable, environmentally friendly services because of urbanisation (Wan 2018).Moreover, because of the advancements in the past thirty years, healthcare systems around the world have seen significant changes, reforms, innovations, and improvements (Durrani 2016).Sufficient access to healthcare is linked to decreased risk of death, especially in older ages (Hao et al. 2020).For example, in the case of a medical emergency, an individual can get assistance faster in the city as there are various methods to contact healthcare facilities for assistance.If someone is unable to contact the facility via phone, they can use the internet.In the case of requiring immediate medical attention, there are several ambulances ready to transfer people to the hospital; as there aren't as many hospitals in the rural areas as there are in the city, therefore, healthcare options and treatments are also restricted relative to the urban environment.

Conclusion
Globally, our world is becoming urbanised day-by-day and an increasing number of individuals are transitioning from traditional rural to industrialised urban lifestyles (Zuo et al. 2018;United Nations 2018).Undoubtedly, urbanisation also comes with costs.Metropolitan settings can result in stressful and sedentary lifestyles, nutritionally imbalanced diets, and other factors that are related to ill health.Moreover, this continuous rise in urbanisation has also been reflected in the structure of the human gut ecosystem, as the diversity of gut microbiota was found to be "very high" in the guts of ancient remote hunter-gatherers as compared to the rural agriculture-based populations and further compared with the urban population (Tasnim et al. 2017;Gupta et al. 2017).Even though urbanisation has contributed to the development of today's urbanised society, there is ongoing research available that describes the association of urbanisation with disease (Br€ ussow 2019).As the gut bacterial community is gained through both vertical transmission (mother to offspring) (Li et al. 2021) and horizontal transmission from the environment (Leeming et al. 2019), therefore, the environment in which we are living may shape the gut microbiota that can effect related health outcomes.By looking at the declining trend of the gut microbiota as society progresses, it is very important for us to understand how this modern lifestyle and the environment is affecting our gut microbiota and ultimately leading us to enter the world of diseases.
Changes in hygiene, diet, early-life microbiota exposure, pollution, and socioeconomic status, as well as other environmental factors, have long-term effects on the human intestine microbiota (Jin et al. 2017;Tanaka and Nakayama 2017;Bowyer et al. 2019).Human knowledge regarding the consequences of urbanisation on the gut microbiome, and its association with health and disease is still very limited (Winglee et al. 2017).Understanding the factors of urbanisation on gut microbiota will help us to minimise the risk of diseases.This review highlights a few of the many factors associated with urbanisation that affect the gut microbiota and health outcomes in different ways.Studies on indigenous and industrialised populations should be continued across the globe to strengthen our understanding and knowledge of how the gut microbiome influences humans in both health and disease conditions, and factors related to urbanisation that can impact health outcomes should be properly considered.Moreover, by better understanding the factors associated with urbanisation and expanding studies across urbanisation gradients, we will be able to determine and introduce new biological and social strategies to prevent and treat diseases and improve health globally.

Disclosure statement
No potential conflict of interest was reported by the author(s).