Abstract
From the emerging studies, the more diverse the microbial population in the gut, the healthier the gut. Health benefits are associated with the functional characteristics of these diverse microbial genes. Extrinsic factors causing dysbiosis are extensively studied however, linking the varying degree of consequences to the respective factors and therapeutic possibilities are not explored at length. This review aims to examine from previous studies and put forward the types of dysbiosis, the immediate consequences and the scientific approaches to restore disrupted microbiota. Dietary supplements are found to be one of the factors contributing profoundly to the alteration of gut microbiota. While diet rich in fibre and fermented food established a diverse microbiome and produce vital metabolites, high fat, animal proteins and high caloric carbohydrate are as well relative to dysbiosis among infants, adult or diseases individuals. The intermittent fasting, feeding methods, the pH and water quality are among the factors associated with dysbiosis. Prebiotics and Probiotics maintain and restore gut homeostasis. Antibiotic-induced dysbiosis are relatively on the spectrum of activity, the pharmacokinetics properties, the dose taken during the treatment route of administration and the duration of drug therapy. The higher the altitude, the lesser the diversity. Extreme temperatures as well are related to reduced microbial activity and metabolism. Delivery through caserium-section deprived the newborn from restoring valuable vaginal bacterial species and the baby will instead assumed intestinal microbiota-like. While exercise and oxidative stress contribute even though moderately, fecal microbial transfer (FMT) also influence gut microbiota.
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Introduction
One of the recent human health and diseases are the factors associated with dysbiosis. Dysbiosis is the reduced diversity of gut microbiota and restoring the lost microbiota to a much diverse composition is eubiosis. Are dysbiosis a result or causation is still in the mystery, partly due to circumstantial or speculative nature of the gut mechanisms. These factors influencing gut microbiota are in a constant flow and the gut with repertoire of microbes is resilient enough to adjust to any variation. In addition to natural variations, the immune system, the intestinal mucosa, microbiota itself, diet and ingested drugs are major factors influencing dysbiosis. What lies illusive until today are the mechanisms underpinning dysbiosis. These mechanisms are not thoroughly explored due to our limited characterizing techniques. The intricate interactions among species such as, the role of parasites, virus, bacteriophages and fungi in addition to natural variations such as, stress, secretions of bacterial toxins etc. when explored, will add weight to the current existing knowledge. Until the science regarding the above pathological effects is bridged to the effects they do cause to dysbiosis, the role of microbiota in health and disease would not be better understood (Travisano and Velicer 2004; Sartor and Mazmanian 2012; Ma et al. 2016).
Vegan’s diet
The debate on vegans eating healthy food better than non-vegans is still strong and to extent a sensitive topic. Considering the bad experiences with food, our apetite can be influenced and this affect the next food to choose. Advertisement, culture or people around can influence what meal we have on the table. Several studies including the one that recruited 15 vegans and 16 omnivores revealed amazing results. Despite, the differences in the serum metabolites between both groups, the gut bacterial community shows insignificant diversity (Wu et al. 2016). This must not be a good news for both the vegans and omnivores group. Furthermore, another randomized trial on 10 human omnivores were on either a high fat and low fibre diet or low fat and high fibre for a period of 10 days corroborated the results of this finding. Again, the microbiome composition has not been shaken and the differences in short chain fatty acid production was not significant. Perhaps the experiments should be extended for a longer period of time. This may assure bacterial derived metabolome to be influenced by being a vegan or not (Wu et al. 2016).
Gluten
Based on the studies of micro nutrients, gluten-free bread reduces the microbiota dysbiosis. Meaning they created a well-balanced microbial community as seen in vitro animal study (Bonder et al. 2016). People with gluten sensitivity or coeliac disease must have welcomed this news after this study was published. 21 healthy people with a profound diversity in the gut microbiota, just after 4 weeks on a gluten-free diet showed a balance diversity. However, among these, are good number who showed a lower abundance of the most common and important microbial species in the gut (Lebwohl et al. 2017). It may be too soon to conclude anything as scientists are still in the lab. In contrast to the coeliac disease related research above, until today, some people avoid gluten and yet they do not have the coeliac diseases or even proven gluten intolerance. In fact, from one of the observational studies, heart diseases were seen with an increasing rate among gluten avoiders (Schroeder et al. 2018). Moreover, it is speculated that perhaps the reduced consumption of whole grains is not good for maintaining the health of some organs. However, more knowledge is required to shed more light on these assumptions.
Dietary gut therapy
With the overfeeding hypothesis, homeostatic are disrupted due to over feeding, leading to dysbiosis, metabolic disorders and diseases (Lachnit et al. 2019; Kim et al. 2014). This is eminent in diet with low-fibre content, easily digestible and energy-dense, all influence the functional genes. Intermittent fasting is ascertained to confer changes in cellular pathways, preventing the development of diseases such as rheumatoid arthritis, obesity, hypertension and asthma, and delay in aging (Longo and Mattson 2014). Human has a set of factors that form mucosal environment and any uncontrolled growth of bacterial population through overfeeding with western-style diet (WSD) impairs carbon to nitrogen to phosphorous ration. Since these diets are easily digestible by both human cells and the microbes, diets rich in sugars, fats, and proteins with small amounts of fiber, lead to imbalance nutrient in the gut. This result to depilation of mucosal barrier and the onset of infections. However, the release of bacterial by-products stimulate the functionalities of immune cells through non-self-recognition of immune reactions thereby initiating immune response (Sakaguchi et al. 2020; Lachnit et al. 2019). This area of research is an inexhaustible discipline and until today, not much has been done especially when it comes to the bad experiences with food. Much often, many people are still struggling with the side effects of popular restrictive diets on gut health. The strict vegans would attest to this and those feeding on raw food or “clean eating” diets, diets free of gluten. Also with side effects are those on FODMAP (fermentable oligosaccharides, disaccharides, monosaccharide, and polyols), irritable bowel syndrome (IBS) treatment alternative diets (Lebwohl et al. 2017).
Antibiotics and drugs
The effects of antibiotics can be attributed to the mode of mechanism, the class of antibiotic, the degree of resistance of the antibiotic used and the dosage used during the treatment. In addition, the route of administration, the pharmacokinetic and pharmacodynamics properties and the spectrum (broad or narrow) all relatively alters gut microbiota composition (Rogers and Aronoff 2016). Non-steroidal anti-inflammatory drugs are commonly used daily however, these are causative agent for stomach ulcers. Among the consequences, metabolic disorders are extensively studied (Freedberg et al. 2015). Microbes themselves are studied to regulate the drug mechanisms. To have a profound insight as to gut dysbiosis, in addition to the type of drugs used, the existing microbiota, immune system and the intestinal mucosa are the prerequisites. While it is understood that only the bacterial communities are explored in the quest to establishing the role of gut in health, other gut microbial species are somehow contributing to the dysbiosis status of the gut microbiota. Until today, long term natural fluctuations such as diseases outbreaks and mutations of the strain might as well rendering alteration to the gut even before antibiotic treatments. Proton pump inhibitors (PPIs), antidepressants, metformin, laxatives and oral steroids are all studied to confer profound dysbiotic effects on the gut.
Prebiotics
Among the well characterized bioactive compounds are phytochemicals and Prebiotics, polyunsaturated fatty acids (PUFAs). Prebiotics have proven to be source of fermentation products such as SCFAs that confer diverse biological benefits to the gut (Hill et al. 2014). While PUFA effects advantage to the host immunity and metabolism, phytochemicals are effective bioactive for anti-inflammatory effects, antioxidants, immune modulatory, anti-carcinogenic and anti-estrogenic effects. In addition to these effects, phytochemicals are studied to exert Prebiotics-like effects on gut, thereby inhibiting pathogenic bacteria. In doing so, they are stimulating the growth of the benign bacteria (Laparra and Sanz 2010).
Oxidative stress
A good number of studies have shown a correlation between increased oxidative stress and reduced gut microbial diversity. The modern dietary habit or the so called western-style diet is rich in fat and refined sugars. These in large quantities, cause an increase of the inflammatory status with reactive oxygen species (ROS) production. Subsequent ROS stimulate the inflammatory cascade (Bellavia et al. 2013). The stress induced by ROS production defined as oxidative stress. Oxidative stress consist of biological system for the process of detoxification and secondary damage repair (Liu et al. 2018). The new study though not supported with enough literature is the potential role of heat shock proteins (HSPs) in the pathogenesis of IBD. HSPs are indentified to play a role in folding, translocation and degradation of intracellular proteins under normal and stressful conditions. They can stimulate an immune response, both innate and adaptive and hence primary targets of the autoimmune response. They are conserved molecules with similar sequences in bacterial and human orthologs (molecular mimicry) (Zhang et al. 2013).
The scoioeconomic status
The variation in diversity and composition of gut microbes is largely determined by the economic status of the country or region the baby is born and a child is raised. This is due to the available food choices left as the options for mothers to feed their babies. It is a fundamental scientific principle that malnourished individuals are prone to unsteady health conditions and this implies to undernourished infants. Infants that are undernourished lead to dysbiosis condition and abundance of enteropathogens such as Enterobacteriacea being prominent in their gut (Reijnders et al. 2016). A comparative analysis done on two separate studies, that involves infants from rural Africa and European children showed pattern that are directly correlating with the type of diet they consume. Diet dominated by starch, plant polysaccharides and fibre enable the abundance in Bacteroides phyla at 57% and Actinobacteria at 10% (Lee et al. 2017). For the European children, due to their diet rich in sugar, animal protein and starch, the abundance of the bacterial population showed a reduce diversity (Alexander et al. 2017). Furthermore, Pretovella, which is a major SCFA were found exclusive to the rural African children microbiota and the same trend is persisting even in healthy human adult consuming high amounts of carbohydrates and some forms of simple sugars (O’Keefe et al. 2015). SCFAs are found to be very significant to the health of gut microbiome and this is manifested in its role in anti-inflammatory mechanisms (Spanogiannopoulos et al. 2016). Furthermore, SCFAs (acetate, butyrate and propionate) are studied to be signaling molecules that help in the maintenance of the integrity of colonic epithelium, lipid metabolism, appetite regulation and glucose homeostasis (Morrison et al. 2016).
However, a decreased condition is found among individual feeding on low MACs, the part of dietary fibre that bacteria in large intestine can feed on (Spanogiannopoulos et al. 2016). Unfortunately, nowadays the abundance of MACs is observed in a decreasing trend in the western diet. The establishment of MACs as a major factor for restoring the gut diversity. Mice supplied with a diet of low MAC results to a massive reduction in their gut microbial diversity (Deehan et al. 2017). There is hope for children affected with under nutrition since the study using gnotobiotic mice ascertained that some microbial species have the power to restore growth impairments transmitted by microbiota isolated from malnourished children (Martínez et al. 2010). Varying causative factors to dysbiosis in the gut microbiota with consequences of which some have alternative therapeutic approaches (Table 1).
When we lose the diversity of our intestinal microbiota, we are prone to other factors that can be internal or external. Dwelling on these factors, at first, the restoration of these diversities needs to be checked. The administration of MACs and in combination of supplementing the missing taxa is studied to be very efficient (Hooper et al. 2003). In line with this intervention, a study that dealt with malnourished children shows correlating results; gnotobiotic mice revealed that, there are specific microbial species found in malnourished individuals that can cause growth impairments. The administration of some missing taxa are seen to have the ability to restore these impairments. If this study holds for similar results, then there is a big hope that microbes can be used to restore growth impairments from malnourished children and hence another new therapeutic intervention in countering the negative effects of under nutrition (Odenyo et al. 2001). Host intrinsic factors such as genetics can influence the microbial population. However it is not well pronounced when compared with the effects of diet and antibiotics on the microbiota. This was in agreement with results emerging from studies on individuals with contrasting geography and locations, twin studies, and people settling in rural and industrial settlements (Ayeni et al. 2018; Vangay et al. 2018).
Dietary interventions to mitigate and establish positive response of our gut microbes would definitely pave a great way as to determining the effects of microbes and our metabolic response. For example, fibre as is a key nutrient for a healthy microbial composition is hoped to remedy series of autoimmune disorders while the fat and sugar are yet to proof beyond any medicinal evidence. From the time of the edition of this review and even beyond, clinical trial based studies are underway and are not far reaching scientific grounds to prevent the human population against autoimmune and inflammatory diseases. The intervention of the Probiotics and Prebiotics and the FMT are also a competing factor to bring in a desirable change in the gut to ascertain a healthy and normal composition. FMT proves C. difficile infection cured more than 90% of cases (Garza and Dutilh 2015).
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Abbreviations
- GI:
-
Gastrointestinal tract
- IBD:
-
Inflammatory bowel diseases
- MACs:
-
Microbiota-accessible carbohydrates
- SCFAs:
-
Short chain fatty acid
- LPS:
-
Lipopolysaccharide
- UC:
-
Ulcerative colitis
- CD:
-
Crohn’s disease
- WSD:
-
Western-style diet
- FODMAP:
-
Fermentable oligosaccharides, disaccharides, monosaccharide, and polyols
- IBS:
-
Irritable bowel syndrome
- PPIs:
-
Proton pump inhibitors
- PUFAs:
-
Polyunsaturated fatty acids
- ROS:
-
Reactive oxygen species
- HSPs:
-
Heat shock proteins
- CLA:
-
Conjugated linoleic acid
- LDL:
-
Low-density lipoprotein
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Additional file 1: Figure 1.
Factors causing alteration to gut microbiota. Diet rich in protein, amimal fats and high carbohydrate, sucralose and diet containing gluten all contributed to dysbiosis. Exercise and intermittent fasting are studied to both starve the bad microbes and clean the gut. Method of delivery for the newborn baby and the feeding methods determine the childhood immunity and this period is crucial for the development of human life. The pH level or water quality are as well among the factors associated with dysbiosis. In addition, drugs including antibiotics, non-steroids anti-inflammatory drugs, Prebiotics and Probiotics adversely affected the gut microbiota composition. Other factors are vitamin D deficiency, oxidative stress, temperature and fecal microbial transfer.
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Ba**ka, O., Tan, Y., Abdelhalim, K.A. et al. Extrinsic factors influencing gut microbes, the immediate consequences and restoring eubiosis. AMB Expr 10, 130 (2020). https://doi.org/10.1186/s13568-020-01066-8
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DOI: https://doi.org/10.1186/s13568-020-01066-8