Yorkie Obesity Exploring the Link Between Gut Health and Weight

Is there a link between gut health and weight loss?

Is there a link between gut health and weight loss? While weve long known that the key to losing weight is a consistent deficit in calories, the latest research shows that there may indeed be a connection between gut health and weight loss too. So could improving our digestive health help us to shed unwanted pounds?

A study published in the Gastroenterology journal suggests that the composition of our gut microbiome could predict how successful we are at achieving our goals. However, scientists are only just beginning to explore this novel gut-weight concept. And its not an easy task.

Our metabolism is a highly complex mechanism. If youve ever embarked on a weight loss journey, you may know that its not as straightforward as energy in versus energy out. How efficient our bodies are at using calories and regulating appetite will depend on a wide range of factors. Some of them cannot be changed, like our genetic make-up or age. But others, like our gut microbiota, can be modified.

If there is a connection between gut health and weight loss, this could open up new possibilities. For example, probiotics and prebiotics could be used in the fight against obesity. But how do these ideas stack up against science?

Here, we discuss what we know so far about the role of gut bacteria in weight management, and look into ways to improve our gut health. And if you want to give your gut bacteria a boost, make sure to check our guide to the best probiotic for useful tips and advice.

What is the gut-weight connection?

Gut hormones

The constant communication between our nervous and digestive systems is central to regulating our metabolism and appetite. Gut hormones play a critical role in this exchange of information, passing on signals of nutritional status from our gut to the brain, so the brain can interpret the bodys energy needs and respond to them accordingly.

Our gastrointestinal system releases over 20 different hormones involved in maintaining energy balance. The levels of these gut hormones depend on a number of factors, including the food we eat, the state of our health, and the compounds produced by the gut bacteria.

Some of these hormones will directly affect our eating behavior. According to the Journal of Obesity, cholecystokinin, peptide YY, pancreatic polypeptide, glucagon-like peptide-1, and oxyntomodulin will suppress your appetite, whereas ghrelin will make you more hungry.

Studies employing advanced neuroimaging techniques have shown how powerful these hormones are at changing our brain activity. Interestingly, one of the aims of a vertical sleeve gastrectomy a procedure in which part of the stomach is removed to restrict the amount of food people can consume is to impact this endocrine appetite control. According to the Annals of Surgery, this type of surgery leads to a marked decrease in the levels of hunger-boosting ghrelin.

Gut hormones are critical to weight loss. Low-calorie diets will inevitably alter their levels to promote appetite and a less efficient metabolism, as reported in the Hormone and Metabolic Research journal. Thats why so many people on weight loss diets may struggle with controlling their appetite and the dreaded yo-yo effect.

Gut microbes and obesity

Is there a link between gut health and obesity? Theres growing evidence that people who carry excess weight tend to have a different composition of gut microbes compared with lean individuals. According to a review published in the Nutrients journal, gut microbiota of obese people may be less diverse and contain less of the beneficial bacterial strains.

However, the Genes & Nutrition journal reports that certain strains associated with obesity and metabolic disorders in Western populations may not have the same effect on Eastern populations. For example, Prevotella and Ruminococcus were obesity-associated genera in studies from the West but lean-associated in the East. Roseburia and Bifidobacterium were lean-associated genera only in the East, whereas Lactobacillus was an obesity-associated strain in the West. Therefore it is unclear whether these differences are a cause or result of excess body weight. More studies are needed to fully understand this issue and what it may mean for weight loss interventions.

There is also mixed evidence when it comes to using fecal transplants as a treatment for obesity, as stated in the Nutrients journal. Fecal microbiota transplantation (FMT) is a procedure in which fecal bacteria is transferred from one individual into another individual. The idea is that the lean persons microbiota will help balance the microbiome of an obese person, triggering weight loss in the process. However, no significant changes in blood sugar levels, BMI or cholesterol were detected in those who underwent this procedure.

Nevertheless, studies have shown that certain microbial by-products tend to be consistently elevated in obese individuals. People carrying excess body weight tend to test more for metabolites like amino acids, lipids and lipid-like metabolites, bile acid derivatives, and other compounds which have been shown to increase the risk of insulin resistance, hyperglycemia, and dyslipidemia.

Gut microbes and weight loss

What does science say about gut health and weight loss interventions? According to a meta-analysis published in the Gut Microbes journal, losing weight tends to result in an increase in the diversity of gut microbes. It also favors the growth of more beneficial strains.

There is also evidence that your gut health may dictate how quickly you are able to shed unwanted pounds. As stated in the Gastroenterology journal, the baseline gut microbiota the composition of gut microbes at the start of a weight loss program may be one of the most important predictors of successful end results.

At the same time, researchers from The American Journal of Clinical Nutrition point out that gut microbes may be quite resistant to change. The scope of these changes may also depend on the type of a weight loss diet. For example, a study published in the Journal of Personalized Medicine points to the Mediterranean diet as potentially the most beneficial.

Physical activity may also change the composition of our gut bacteria. According to a review published in the Nutrition, Metabolism & Cardiovascular Diseases journal, exercise can promote the growth of the beneficial strains, while decreasing the obesity-related Proteobacteria.

So there is certainly a strong link between gut health and weight loss, but we still do not know what truly works, and what doesnt. Having said this, we have a good understanding as to which individual foods can benefit our gut health and taking care of our little intestinal residents can benefit our body nonetheless.

What are the best foods for gut health?

Foods rich in dietary fiber:

• Fruits
• Vegetables
• Wholegrains
• Beans
• Legumes
• Avocado

Foods rich in probiotics:

• Fermented dairy products, such as yogurt and kefir
• Fermented soya products, such as tempeh and natto
• Miso soup
• Sauerkraut
• Kimchi
• Kombucha

Foods rich in prebiotics:

• Garlic
• Onions
• Chicory root
• Chickpeas
• Artichokes
• Beans
• Leeks
• Bananas
• Oats
• Almonds

Do probiotics help with weight loss?

Can you take probiotics to lose weight? It is difficult to answer this question with certainty. The science exploring the links between probiotic supplementation and weight loss is still in its infancy.

It may largely depend on the type of bacterial strains used. According to a review published in the International Journal of Obesity, these include Lactobacillus plantarum, Lactobacillus rhamnosus, Lactobacillus curvatus, Lactobacillus gasseri, Lactobacillus amylovorus, Lactobacillus acidophilus and Lactobacillus casei. However, they may need to be combined with a low-calorie diet to bring about the best results. Scientists are also investigating the potential of lesser-known Akkermansia strains. As stated in a review published in the Archives of Physiology and Biochemistry, they may help manage obesity and associated metabolic complications.

This article is for informational purposes only and is not meant to offer medical advice.

The Influence of the Gut Microbiome on Obesity in Adults and the Role of Probiotics, Prebiotics, and Synbiotics for Weight Loss

INTRODUCTION

The prevalence of several chronic diseases are growing worldwide; of these, obesity is the primary culprit and has been major concern for decades (Gentile and Weir, 2018; Wilkins et al., 2019). Although several methods for treating excessive weight gain are used, obesity remains a major public health problem, which requires novel nutritional and/or medical solutions. Being overweight [body mass index (BMI) between 25 and 30 kg/m²] or obese (BMI higher than 30 kg/m²), and the related comorbidities (cardiovascular diseases, diabetes, and cancer) are leading causes of death; thus, researchers strive to find novel efficient treatments for these conditions (Wilkins et al., 2019). A high-calorie diet is a causal factor for obesity and may induce changes in the function of the gut microbiome (Guirro et al., 2019). In addition to nutritional, lifestyle and genetic factors, it has been suggested that obesity may also result from perturbation of the gut microbiome, which affects metabolic function and energy homeostasis (Guirro et al., 2019).

Approximately 10¹⁴ bacteria and archaea of more than 1,000 species exist in the human gastrointestinal tract; together, these are known as the gut microbiota (Lv et al., 2019). The impact of the gut microbiome on health has been a major focus of interest for the past couple of decades, since an adequate gut microbiota and probiotic supplementation have positive effects on many health conditions, including type 2 diabetes, cardiovascular diseases, and immune and infectious diseases (Mohajeri et al., 2018; Valdes et al., 2018). The role of the gut microbiome in affecting the wellbeing of individuals is encouraging researchers to find new treatments for different health conditions, such as obesity and weight gain. A reciprocated relationship exists between the gut flora and diet, whereby dietary factors regulate the role and structure of the microbiota. Microbes in the human intestines impact the absorption, breakdown, and storage of nutrients, and have potential consequences on host physiology (Gentile and Weir, 2018). Furthermore, overuse of antibiotics has been linked to the onset of obesity (Podolsky, 2017; Leong et al., 2018). Gut dysbiosis (an imbalance of gut microbiota composition) due to dietary or environmental changes can promote overgrowth of pathogenic organisms that cause chronic inflammation, thereby playing a major role in the pathology of chronic metabolic and intestinal diseases (Turroni et al., 2014). In contrast, a healthy balance of intestinal microbiota may play a role in preventing or alleviating obesity and metabolic diseases (John and Mullin, 2016). Increases in certain beneficial bacterial species and decreases in other damaging species may impact the health and the wellbeing of the host (Fischer and Relman, 2018).

Gut microbiota may also play a role in the brain and the central nervous system, which may help explain relationship between the gut microbiota and overall health (Lankelma et al., 2015). The gut, referred to as the second brain, is composed of trillions of microorganisms that directly affect the brain and brain signals, influencing stimulants for hunger and appetite. The diversity and composition of the gut microbiome are influenced by multiple factors, such as birth mode, dietary habits, the use of antibiotics and medications, aging, and other environmental factors (Azad et al., 2016). Human microbial colonization commences at birth, and then progresses and modifies species profusion for 3 years until the microbiota grows into its adult form. The human microbiota is composed of 5 different families of microbiota (Bacteroidetes, Firmicutes, Actinobacteria, Proteobacteria, and Verrucomicrobiai, of which the Bacteroidetes and Firmicutes make up 90% of the species of bacteria (Lv et al., 2019).

This review will discuss the relationship between the gut microbiota and obesity, to increase understanding of the mechanism by which the gut microbiome affects weight gain. Moreover, this review will examine the effects of probiotics, prebiotics, and synbiotics supplementation on body weight.

RESULTS AND DISCUSSION

Obesity and the gut microbiome

The prevalence of obesity has increased worldwide; sedentary lifestyles and increased consumption of food are considered the primary causes for this epidemic (Baothman et al., 2016). The main physiological functions of the gut microbiota are digestion, vitamin synthesis, and metabolism. It has been reported that the gut microbiota increases energy production from food, provides low-grade inflammation, and impacts fatty acid tissue composition. These mechanisms may link the gut microbiota with obesity (Baothman et al., 2016; Duca et al., 2018).

Animal studies: Obese subjects tend to have a greater amount of Firmicutes species, and a higher Firmicutes to Bacteroidetes ratio than individuals of normal weight (John and Mullin, 2016). Firmicutes have been shown to be negatively proportional to resting energy expenditure, whereas Bacteroides have been shown to be positively correlated with the percentage of body fat (Gomes et al., 2018).

A large depletion of Bacteroides species are present in obese mice, including Bacteroides thetaiotaomicron, which protects against adiposity. Transfer of B. thetaiotaomicron to mice that received a normal diet resulted in a significant reduction in total fat, and prevented weight gain in mice that received a high fat diet (Liu et al., 2017). Mice that received a high fat diet and were supplemented with B. thetaiotaomicron also had increased levels of bacteria of the Akkermansia genus (Liu et al., 2017). Akkermansia muciniphila have been linked to lower subcutaneous adiposity diameters, waist to hip ratios, and fasting blood glucose levels (Dao and Clment, 2018). A. muciniphila have also been shown to counteract inflammation and adiposity after consumption of a high fat diet in rodent models (Schneeberger et al., 2015). A. muciniphila produce acetate and propionate, which can be used as sources of energy by other species of bacteria (Schneeberger et al., 2015). Furthermore, this phylum may also induce a noticeable improvement in insulin sensitivity (Dao and Clment, 2018) and host metabolism (Dao et al., 2016), thus preventing and alleviating obesity.

Surprisingly, high-fat diets (HFD) and high-sucrose diets (HCD) may have different effects on the gut microbiota. Kong et al. (2019) studied obese mice that received either a HFD, HCD, or normal diet for 13 weeks. During the last 4 weeks of the intervention, mice received probiotics consisting of Lactobacillus acidophilus, Bifidobacterium longum, and Enterococcus faecalis in a 1:1:1 ratio. Mice that received the HFD or HCD showed increases in body weight during the first 9 weeks; however, once probiotics were introduced during the last 4 weeks, weight gain slowed in both groups. Furthermore, the HCD and HFD had different effects on the gut microbiota (Kong et al., 2019). The HFD tended to decrease the diversity of the gut microbiota, whereas the HCD completely changed the structure of the bacteria related to obesity. Some favorable bacteria (Allobaculum, Bifidobacterium, Olsenella, Faecalibacterium, and Ruminococcus) were reduced in the microbiota of mice that received the HFD, whereas significantly more obesity-related bacteria (Acinetobacter, Blautia, and Dorea) were observed in the HCD group. Following ingestion of probiotics, Allobaculum, Lactococcus, and Bifidobacterium were significantly increased in both groups. Kong et al. (2019) suggested that dietary sucrose impacts the obesity-induced intestinal microbiota to a greater extent than dietary fat.

Supplementation of obese mice with other species of bacteria, such as Lactobacillus plantarum, reduces adipose deposition and upregulates expression of lipid oxidative genes compared with the control group (Park et al., 2017); this suggests that these species of bacteria may be used in combination with dietary management to treat obesity. In addition, anti-obesity effects of administering specific species of Lactobacillus sakei from probiotics were observed in obese murine models (Ji et al., 2019a; Ji et al., 2019b). However, further studies are needed to better understand the mechanism by which Lactobacillus species reduce fat storage in human.

Human studies: Microbial diversity shows a preventive effect on long-term weight gain in healthy individuals (Menni et al., 2017). Microbial composition differs between people; for example, most studies have noted that the ratio of Firmicutes to Bacteroidetes is significantly higher in obese subjects (John and Mullin, 2016). Furthermore, previous studies have shown correlations between an increased amount of Bacteroidetes in stools and weight loss, and between Firmicutes and development of obesity (Ley, 2010; John and Mullin, 2016).

In addition, a study was performed to report the differences in gut microbiota between obese and non-obese Japanese subjects. Obese subjects had significantly reduced numbers of Bacteroidetes and higher Firmicutes to Bacteroidetes ratios compared with non-obese subjects. The diversity of the bacteria was also significantly greater in the obese subjects than the non-obese subjects (Kasai et al., 2015).

In a study of obese and lean Chinese college males, there was a negative correlation between BMI and gut microbiota diversity. Therefore, obese male subjects had a less diverse microbiome than individuals in the lean group. In addition, fecal microbial composition was more complex for lean males and contained a higher ratio of Bacteroides to Firmicutes (Lv et al., 2019).

Interestingly, aside from a higher number of Firmicutes in obese subjects, a recent study noted that overweight and obese individuals who start therapy with high Firmicutes/Bacteroides ratios have better health outcomes when following a high fiber and whole grain diet than those with low Firmicutes/Bacteroides ratios (Hjorth et al., 2018).

Ley (2010) suggested that obese participants receiving a low caloric diet for 12 months show increases in Bacteroidete counts associated with weight loss. However, contradictory data exists regarding Bacteroidetes species in the gut flora of obese compared with non-obese individuals, with other studies showing no correlation or even a positive correlation with obesity (Schwiertz et al., 2010). Such discrepancies between studies may be due to host physiology and/or various dietary habits, as well as the techniques used for analysis.

The remarkable effect of A. muciniphila on metabolism has also been observed in human studies. A. muciniphila have shown protective effects against gut permeability and endotoxemia, to reinforce the immune system, and to improve glucose homeostasis. Thus, individuals with higher amounts of A. muciniphila have a better status of health (Dao et al., 2016).

Mechanism of action

Change in energy harvest and nutrient metabolism: The gut microbiome can be associated with carbohydrate and lipid metabolism. Despite a reduced food intake, transplantation of normal mouse microbiota into germ-free mice increases body fat content (by 60%) and insulin resistance within 14 days, and increases triglyceride levels through activating de novo fatty acid synthesis (Bckhed et al., 2004). One important function of the gut microbial function is the ability to alter bile acid signaling and to produce distinct pathophysiological bile acid profiles (Sanmiguel et al., 2015). Approximately 510% of bile acids are bio-transformed by anaerobic gut microbiota (Bacteroides, Eubacterium, and Clostridium), with the rest secreted in faeces. This demonstrates the role of the gut microbiome in the digestion and metabolism of dietary fat (Mazloom et al., 2019).

The gut microbiome has also been linked to metabolism of essential amino-acids (EAA). Genetic biomarkers relating to EAA metabolic pathways are significantly increased in germ-free murine recipients of the obese-twin gut microbiome. The germ-free recipients of lean-twin microbiomes were found to be richer in genes relating to the breakdown and fermentation of dietary polysaccharides (Ridaura et al., 2013). These results emphasize the major of the gut microbiome in the breakdown and metabolism of macronutrients in the human diet. Diet is a crucial contributor to microbial change; however, the exact dietary interventions that increase microbiota diversity and affect metabolic state vary between individuals (Stephens et al., 2018).

Nitrogen, a major source of dietary protein, is essential for microbial growth, assimilation of carbohydrates, and assembly of short chain fatty acids (Zhang et al., 2018). Hence it is crucial to consume a varied diet with adequate daily intake of protein from different food sources.

Short chain fatty acids (SCFAs): The gut microbiota plays a role in energy metabolism through production of SCFAs. SCFAs are produced by colonic fermentation involving anaerobic catabolism of dietary fiber and protein (Baothman et al., 2016; Zhang et al., 2018). SCFAs are microbial waste products produced by microbes to balance homeostasis of the gut (Baothman et al., 2016). SCFA, specifically acetate, propionate, and butyrate, may have an impact on human metabolism. The beneficial effects of these products have been observed on body weight, insulin sensitivity, and glucose balance. SCFAs are also able to strengthen the intestinal barrier, thus reducing inflammation, and have a positive effect on lipid metabolism (Chambers et al., 2018). SCFAs are able to regulate satiety and reduce appetite (Hamilton and Raybould, 2016; Li et al., 2018), thus playing a major role in food intake and energy consumption. Furthermore, SCFAs are able to act on free fatty acid receptor 2 to stimulate the release of the hormone peptide YY (PYY), thus playing a direct and significant role in inducing satiety (Brooks et al., 2016).

The quantities of SCFA differ in overweight or obese subjects compared with lean subjects: obese individuals had higher amounts of (Fernandes et al., 2014) fecal butyrate, acetate, and propionate produced by Bacteroidetes species (Baothman et al., 2016) compared with lean individuals. Previous studies have shown that dietary supplementation with butyrate decreases insulin resistance (via increasing mitochondrial function and energy expenditure) and is protective against obesity caused by high calorie diet (Lin et al., 2012; Baothman et al., 2016). Consumption of higher-quality whole grains or bran can increase butyrate production, thus helping increase the biodiversity of the gut microbiota (McClave and Martindale, 2019).

In summary, SCFA are known for their advantageous modulatory effects on human immunity, gastrointestinal epithelial cell integrity, lipid metabolism, glucose homeostasis, and appetite (Tandon et al., 2019).

Inflammation: Gut bacteria may alter inflammatory factors by modulating inflammatory cytokine secretion. High levels of interleukin (IL)-6, tumor necrosis factor (TNF), and C-reactive protein are biomarkers for inflammation and appear to be associated with obesity (Rastelli et al., 2018; Singer-Englar et al., 2019). Probiotic studies have shown that a decrease in inflammatory factors (IL-6 and TNF) lower inflammation, which makes this pathway clearer for interpreting the impact of probiotics on obesity. Moreover, Chang et al. (2019) has stated that studies have identified several potential next generation probiotics due to rapid development of advanced genetic sequencing tools: Bacteroides fragilis decreases inflammation and Parabacteroides goldsteinii is a potential anti-obesity probiotic.

Chang et al. (2019) and Wu et al. (2019) have shown that water extract from Hirsutella sinensis, a medicinal mushroom, decreases obesity, insulin resistance, and inflammation in HFD fed mice. The isolated polysaccharides within the water extract also reduced body weight by 50%. Analysis of the gut microbiota showed that Gram-negative P. goldsteinii was decreased in the microbiome of HFD-fed mice, whereas this bacterium was elevated in mice treated with mushroom polysaccharides. These results demonstrated the effectiveness of mushroom polysaccharides for mediating including the recently identified probiotic P. goldsteinii and anti-inflammatory, anti-obesity, and anti-insulin resistance biomarkers (Chang et al., 2019; Wu et al., 2019). H. sinensis polysaccharides and the gut bacterium P. goldsteinii may be described as prebiotics and probiotics useful for the treatment of obesity.

Antibiotic use and dysbiosis: Use of antibiotics is correlated with an increased risk of developing multiple inflammatory disorders (Le Roy et al., 2019a) and has been linked to alterations in the gut microbiome (Hamilton and Raybould, 2016). Antibiotic-induced dysbiosis induces weight gain and increases very low-density lipoprotein/high-density lipoprotein ratios in animal studies (Le Roy et al., 2019b). Moreover, exposure to antibiotics at 2 years of age increases the likelihood of developing obesity later in life (Stark et al., 2019), and alterations to the gut microbiota after use of antibiotic may lead to weight gain (Podolsky, 2017; Leong et al., 2018; Stark et al., 2019). However, how antibiotic-induced changes to the microbiota increase the risk of inflammation and weight gain in humans is currently uncertain.

Hormone and neurotransmitter secretion: Bacterial dysbiosis, related to increases in the Firmicutes species (Clostridium, and Eubacterium rectale, Clostridium coccoides, Lactobacillus reuteri, A. muciniphila, Clostridium histolyticum, and Staphylococcus aureus) has been linked to alterations in gastrointestinal peptides (gastrin, cholecystokinin, somatostatin, and ghrelin). Eventually, these changes may result in decreased satiety and increased appetite and food intake (Gomes et al., 2018).

Probiotics and prebiotics effect on obesity and weight gain

Use of probiotics and prebiotics as a prevention and treatment for different chronic diseases has largely increased in the last decade (Cerd et al., 2019). Synbiotics (supplements including probiotics and prebiotics that may have a beneficial effect on health) are now often used as functional foods (nutraceutical supplemental additives for healthy eating). Emerging evidence has demonstrated that probiotics may be organic compounds of the microbiome and may ameliorate its function (Wang et al., 2019b).

Probiotics: Probiotics consist of live bacteria, typically Lactobacilli and Bifidobacteria, beneficial for improving the composition of colonic microbiota and promoting health of the host (Okeke et al., 2014; Qian et al., 2019).

Animal studies: In a previous study, obese mice were fed one or more strains of probiotics (Lactobacillus rhamnosus, Bifidobacterium breve, and Lactobacillus paracasei) or placebo. Mice receiving probiotics showed decreased levels of serum lipopolysaccharides (LPS), neutral lipids in the liver and IL-6 (Plaza-Diaz et al., 2014). Deconjugation of bile acids by SCFA may explain reductions in fat mass observed in individuals consuming probiotics, due to fermentation of non-digestible carbohydrates (Brusaferro et al. 2018). These findings indicate probiotics are highly effective for improving BMI and body weight and for increasing fat loss, and suggest that altering the gut microbiome with probiotics is more predictable.

Chemerin has recently been recognized as an adipokine that plays a major role in the metabolism of adipocytes and increases adipogenesis. elik and nl St (2019) evaluated the impact of probiotic supplementation on levels of chemerin, inflammation, and metabolic syndrome parameters in obese rats. Rats were fed either a control diet, a HFD, or a HFD supplemented with probiotics after induction of obesity. Weight and changes in weight and BMI were statistically different in the obese intervention group compared with the control group. Rats in the obese group also exhibited increased fasting plasma glucose, insulin and insulin resistance, inflammatory markers, and leptin compared with the control groups. Treatment with probiotics decreased weight gain significantly; these positive effects were observed at the level of insulin and fasting blood glucose, inflammatory markers, leptin, and chemerin levels (elik and nl St, 2019).

Human studies: Use of probiotics has been shown to reduce BMI and total body fat, specifically visceral fat (Osterberg et al., 2015; Mazloom et al., 2019). A clinical study conducted by Osterberg et al. (2015) showed that probiotics prevented increases in body weight and body fat in 20 healthy males who consumed a high fat diet for 4 weeks.

A meta-analysis was conducted to examine the effect of probiotics on body weight and glycaemic control in overweight or obese adults. Adults who received probiotics had significant reductions in body weight, BMI, waist circumference, fat mass percentage compared with adults in the control group (Wang et al., 2019b). A greater reduction in fat mass was observed with 1) use of high versus low doses of probiotics, 2) probiotics of a single strain versus multiple strains, and 3) probiotics administered in the form of foods compared with capsules or powder. In addition, when compared with the control group, individuals in the probiotic groups had reduced insulin levels. Overall, Wang et al. (2019b) and Koutnikova et al. (2019) claim that use of probiotics both has a positive effect on weight loss and improves other metabolic parameters.

Probiotics containing Lactobacillus and Bifidobacterium appear to have some benefit for gram negative gut bacteria, thus preventing overgrowth of pathogenic bacteria in the flora (Okeke et al., 2014). In addition, probiotics can improve the intestinal epithelial barrier and reduce gut permeability, which is a major factor in preventing inflammation and endotoxemia due to transfer of foreign bodies into blood (He and Shi, 2017). SCFA play a key role in this process. Moreover, since dietary therapy may alter the function and composition of microbes found in the gut, it has an influential benefit on the host (Koutnikova et al., 2019; Qian et al., 2019). In a study done by Qian et al. (2019), subjects were randomly assigned to four groups: HFD; dietary intervention (DI), in which the HFD was replaced by a low-fat diet; HFD with probiotics (L. acidophilus, B. longum, and E. faecalis); or DI with probiotics. Fecal samples were obtained after 4 months and 16S rDNA sequencing was carried out to pinpoint how probiotics with DI change the microbiota composition. Results showed that the combination of probiotics with DI raised microbial diversity, as compared with individual application, of the two butyrate-producing families Ruminococcaceae and Lachnospiraceae. Moreover, they observed a reduction in the ratio of Bacteroidetes/Firmicutes in those with HFD-obesity, which may be inversely increased by diet adaptation. Various studies have indicated that this ratio is not a causal factor in human obesity but may be related to dietary intake. Thus, intake of probiotics with DI appeared to expand the phyla of beneficial species, and reduce that of certain harmful species, providing a natural possibility to treat HFD-obesity (Cerd et al., 2019; Qian et al., 2019). Studies conducted on probiotics and their effect on obesity causing factors are briefly summarized in .

Table 1

Studies of the effects of probiotics on indicators of obesity

Possible mechanism of probiotics: Supplementation with probiotics may increase SCFA-providing bacteria, reduce quantitative LPS producers, and reduce tissue loss and organic inflammation caused by LPS. Opportunistic pathogens with their metabolites (trimethylamine, LPS, and indole) are also reduced by probiotics. Probiotics may also inhibit fat accumulation, reduce inflammation and insulin resistance, and regulate neuropeptides and gastrointestinal peptides (Sivamaruthi et al., 2019; Wang et al., 2019b).

Prebiotics: Traditionally, prebiotics were considered to be non-metabolized food ingredients, which reach the intestinal lumen and are selectively utilized by beneficial microbes in the host (Tandon et al., 2019; Wiese et al., 2019). Inulin, galacto-oligosaccharides (GOS), and fructo-oligosaccharides (FOS) are the most frequently analysed prebiotic supplements in recent studies (Wiese et al., 2019). Fermentable carbohydrate inulin is able to increase the density of cells that produce the appetite suppressing hormone PYY by 87%, thus showing its role in reducing food intake and enhancing obesity treatment (Brooks et al., 2016). Supplementation with GOS in healthy individuals have been shown to raise the number of Bifidobacterium spp. and decrease the number of Bacteroides (Davis et al., 2011). Further, studies examining prebiotics have indicated that these compounds promote changes in both the composition and function of the gut microbiota. Prebiotics increase the number of Bifidobacterium species and other butyrate producers, leading to improvements in metabolic outcomes and the gut barrier against pathogens (Beserra et al., 2015). In other studies, this increase in Bifidobacterium has been shown to be accompanied by a rise in Lactobacillus species following addition of FOS, resulting in a decline in ghrelin levels, PYY, and food intake (Gomes et al., 2018).

FOS is known for its bifidogenic capabilities (Gomes et al., 2018; Wiese et al., 2019). In a randomized, double-blinded, placebo-controlled trial, human subjects received FOS at three dose levels (2.5, 5, and 10 g/d) or placebo (maltodextrin 10 g/d) with microbial DNA extracted from fecal samples at specific time-points (Wiese et al., 2019). FOS consumption increased the phyla of Bifidobacterium and Lactobacillus. Moreover, higher doses of FOS promoted selective proliferation of phyla belonging to Lactobacillus. However, withdrawal of prebiotic consumption reduced the abundance of this phyla. Furthermore, there was a significant change in certain butyrate-producing microbes (Faecalibacterium, Ruminococcus, and Oscillospira). These results indicate that prebiotic consumption reinforces microbial diversity and has beneficial effects on the health of the host (Wiese et al., 2019).

In addition, high fat diet-induced leptin resistance is improved by a single dose of prebiotic treatment. Bifidobacterium and GOS, studied alone and as synbiotics, showed no additional benefit when used together (Krumbeck et al., 2018). Clinical trials investigating their use in the treatment of obesity are still on-going. Several studies have reported that cocoa flavanols, dark chocolate (DC), and lycopene have a systemic effect on gut microbiota and a prebiotic potential. A study of obese subjects (Wiese et al., 2019) showed regular intake of lycopene for one-month, with or without DC, resulted in significant alterations in the composition of the gut microbiome. The lycopene formulations prompted a dose-depended rise in mainly Bifidobacterium species. Whereas in the DC formulation, there was a rise in Lactobacillus. In addition, these formulations led to a significant decrease in Bacteroidetes (Wiese et al., 2019). In conclusion, sufficient data on the effect of these prebiotics on weight reduction are still unavailable.

Obesity treatment methods and gut microbiome

Dietary intervention: Different diets have different influence on intestinal microbial composition and diversity (Oriach et al., 2016), which can contribute to onset of inflammatory diseases during adulthood. The effect of different dietary interventions for treatment of obesity on the gut microbiome are briefly summarized in . The correlation between different diets and their effects on obesity may be interpreted by the consequence of each diet on the gut microbiota and different mechanisms by which gut bacteria may affect body weight.

Table 2

The influence of different modalities of obesity treatment on gut microbiome diversity and composition

Westernization of dietary habits has led to microbial dysbiosis (Noble et al., 2017). Studies have revealed that African children who consume low fat/high fiber diets have a higher diversity of intestinal microbes and fewer pathogenic bacteria. These children also have larger amounts of Bacteroidetes than European children, who have higher amounts of Firmicutes and Enterobacteriaceae (Shigella and Escherichia) (De Filippo et al., 2010). In contrast, a high fat/low fiber diet has been shown to reduce intestinal microbial diversity (Simpson and Campbell, 2015), protective gut bacteria and SCFA (Agus et al., 2016). Dietary intake of high fiber foods (e.g. fruits, vegetables, and legumes) increased microbial diversity (Simpson and Campbell, 2015; Zhang et al., 2018), and was associated with reduced weight gain in humans, independently of energy intake (Menni et al., 2017).

Finally, Astaxanthin, an antioxidant derivative of carotenoids, and the medicinal mushroom Antrodia cinnamomea has been shown to enhance gut microbiota in obese mice induced by a HFD; both prevented weight gain, improved lipid and glucose metabolism, and regulated the gut microbiota (Chang et al., 2018; Wang et al., 2019a), through optimising Bacteroides to Firmicutes ratios and enhancing Akkermansia (Wang et al., 2019a).

Exercise: Behavioural and environmental changes can regulate the activity and structure of the gut microbiota. Studies have shown that aerobic exercise enhances microbial variation (largely bacteria producing butyrate) and increases the turnover of macromolecules, specifically carbohydrates and proteins, in the gut microbiome of athletes (Allen et al., 2018). A cross sectional study performed by Whisner et al. (2018) compared changes to gut microbial diversity and composition in young adults who undertake moderate-to-vigorous physical activity (MVPA). The study found increases in microbial diversity, especially in participants who received an adequate amount of fiber per day in addition to MVPA. This change has been observed in other studies; furthermore, an increase in Bacteroidetes and decrease in Firmicutes has been reported in obese adults following aerobic moderate-to-intense physical activity (Santacruz et al., 2009). In a study by Allen et al. (2018), sedentary lean and obese subjects participated in a 6-week endurance exercise program, which included 30 to 60 min of moderate-to-vigorous workouts. Fecal samples were taken at baseline and post intervention. Results showed that physical activity altered the gut microbiome, and that these changes were dependent on obesity status. The regimen increased fecal levels of SCFA (acetate and butyrate) in lean subjects but not in obese subjects. However, exercise did reduce body fat percentage in both groups. In summary, exercise induced compositional and functional changes to the human gut microbiota dependent on obesity status and exercise sustainment, and independent of diet.

To conclude, it is currently unclear whether exercise confers benefits for health by altering the gut microbiota as there is a lack of well-designed and prospective controlled trials.

Other therapeutic methods:Obesity non-nutritive therapies have been shown to alter the diversity and composition of the gut microflora. The medication metformin has been shown to induce increases in A. muciniphila (Maniar et al., 2017). Moreover, bariatric surgeries induced changes to the gut microbiome that could last for a decade, and induced a significant increase in Bacteroides species (Liu et al., 2017). Patients who undergo Rouex-en-Y gastric bypass (RYGB) experience enhanced metabolism that cannot be explained by caloric restriction and weight loss alone.

Alterations to the gut microbiome play a role in shifting bacterial composition (Baothman et al., 2016). This has been demonstrated by Liou et al. (2013) whom demonstrated that transplantation of fecal matter from RYGB- treated mice to germ-free mice caused a decrease in weight and fat mass in the latter.

Furthermore, Aron-Wisnewsky et al. (2019) performed a study on severely obese subjects who were candidates for bariatric surgery. In these subjects, improvements in metabolism and inflammation were observed following microbiome modification. The effects of different therapeutics that affect the gut microbiome for treating obesity are briefly summarized in .

Finally, multiple factors impact the diversity and composition of the gut microbiota and may lead to dysbiosis, which is associated with weight gain and obesity. Specifically, diet, physical activity, dietary supplementation, medications, and bariatric surgery affect the gut microbiome. The influence of the intestinal microbiome on metabolism, hormone balance, neurotransmitter function, and the brain can play a major role in weight management and treatment of obesity. Moreover, the use of probiotics and prebiotics improves gut bacterial composition, and has achieved promising outcomes for prevention and treatment of obesity.

Further studies are needed to determine the ideal formulation(s) for supplementation, identify the populations of obese patients who may benefit from gut microbiome modulation, and to assess the durability and long term impact of probiotic and prebiotic supplementation on obesity and health.