A brief overview on the use of probiotics to treat overweight and obese patients

KEYWORDS:

• Obesity
• Probiotics
• Lactobacillus
• Bifidobacterium; Metabolic syndrome
• Expert review

1. Introduction

World Health Organization and Food and Agricultural Organization of the United Nations defined probiotics as ‘Live microorganisms which when administered in adequate amounts confer a health benefit on the host’ [1]. Beneficial effects of consuming probiotics in the improvement of intestinal flora balance have been shown in many studies and needless to mention, occurrence of probiotics adverse effects differs in different populations and as a health complication should be considered carefully [2].

Table 1. Human and animal studies of gut microbiota.

Author/Year	Type of Study	Investigated Mechanism	Study Result
Turnbaugh et al. 2006 [6]	Human study	Alteration in F/B ratio Methylation and expression of obesity and CVD related genes	Increased capacity to harvest energy as a result of hormonal changes
Haro et al.2016 [7]	Human study	Alteration in F/B ratio	Alteration through changes in Bacteroidetes in men and alteration through changes in Firmicutes in women
Turta et al.2016 [8]	Human/Animal study	Dysbiosis of the gut’s normal flora Interfering the development of gut microbiota	Transmission of maternal vaginal flora during delivery to the baby Childhood/life time central obesity as results of exposure to antibiotics during prenatal period
Del Chierico et al. 2014 [9]	Human study	Escalating the amount of Lactobacillus, Bifidobacterium, and Prevotella and also reduced the amount of Clostridium	Obesity and deterioration of lipid profile while using Mediterranean diet
Reijnders et al. 2016 [11]	Human study	Upregulation of adipose tissue gene expression of oxidative pathways and downregulation of immune-related pathways	Antibiotic-induced obesity through gut microbiota dysbiosis
Sotoudegan et al. 2019 [5]	Animal study	Dysbiosis of the gut’s normal flora	Transmission of maternal flora or probiotics through lactation
Ley et al.2005 [12]	Animal study	Dysbiosis of the gut’s normal flora through maternal abundance of the dominant gut microbiota	Obesity and harvesting energy from carbohydrate-rich food
Bäckhed et al. 2007 [13]	Animal study	Expression Of AMPA And Fiaf	Weight gain from foods containing fat and carbohydrate

The human normal flora contains microorganisms that can be found on the skin, oral, vaginal and nasal cavities, and also in the colon. More bacteria are present in the intestine which play an essential role in the metabolism, especially carbohydrate fermentation. Prebiotics, probiotics, diet, antibiotics, and surgery may alter gut microbiota, which directly have an impact on the prevalence of metabolic diseases and obesity [3].

Increasing prevalence of obesity is a worldwide concern, and obesity is defined as excessive amounts of fat in the body, mainly visceral fat, measured by body mass index (BMI: weight in kilograms divided by height in meter squared) and stems from an imbalance of energy intake and expenditure. The J shape diagram of BMI and morbidity/mortality risk is revealed in many studies [4]. Increased BMI greatens risk of hypertension, dyslipidemia, cardiovascular diseases (CVD), diabetes, gallstones, inflammatory skin diseases such as psoriasis and atopic dermatitis and atherosclerosis, as well as some types of cancers [3,4].

Recently, the gut microbiota is seen as an extra contributing factor in the pathophysiology of obesity [1–4]. Changes in the redundancy of Bacteroidetes and Firmicutes as dominant bacterial divisions have been implicated in the role of the gut microbiota in obesity. To understand the therapeutic role of probiotics, especially Lactobacillus, and Bifidobacterium in adjusting gut dysbiosis has been examined to find out their intestinal microbiota balance capacity and management of obesity [3,4]. In the present study, PubMed and clinicaltrials.gov searching databases were used to find studies undertaken over the past two decades. The following keywords, either alone or in combination: obesity, probiotics, Lactobacillus, Bifidobacterium, metabolic disease, over-weight were used. The main aim of this study has been to consider the role of probiotics in the treatment of obesity as a metabolic disease.

2. Gut microbiota and obesity

In obesity as a metabolic-associated disease, the balance of gut microbiota and baseline ratios of normal flora disturbs, to illustrate, in over-weight patients, the baseline ratio of two dominant bacterial divisions (Firmicutes to Bacteroidetes) becomes greater [2–13]. Firmicutes consist of more than 274 genera such as Bacillus, Lactobacillus, Mycoplasma, and Clostridium and also there are about 20 genera of Bacteroidetes including Bacteroids. Moreover, some studies reported controversial data about the impact of Bacteroidetes on the development of obesity [3,4].

Three main possible mechanisms of gut microbiota balance to modulate body weight are reported; short-chain fatty acid (SCFA) production, regulation of bile acid metabolism, and induction/protection from metabolic endotoxemia. In addition, SCFAs are produced through fermentation of starch, unabsorbed sugars, cellulosic and non-cellulosic polysaccharides, and mucins that controls directly the lipid metabolism and energy harvesting. Also, apoptosis of adipocytes and a decrease in fat accumulation occurs through inhibition of insulin signaling pathways by SCFAs [4,5].

2.1. Human studies

Increased amounts of Firmicutes to Bacteroidetes results in methylation of the genes which are related to obesity and CVD in order to promote gene expression and also it leads to impact hormones that influence metabolic function through increased capacity to harvest energy [6]. Indeed, F/B ratio differs by gender and BMI, e.g. men with BMI >33 amount of Bacteroidetes decreases while in women no changes in Bacteroidetes were reported and as a substitute, the overall changes in the ratio seemed to be higher in women through high amounts of fluctuation of Firmicutes [7].

Also, exposure to broad-spectrum or narrow range antibiotics during pregnancy or prenatal periods plays a vital role in childhood or lifetime central obesity and fat accumulation (large hiatal hernia) through dysbiosis of the gut’s normal flora or interfering the development of gut microbiota in the baby [8].

In the Mediterranean diet consumers, obesity and lipid profile deteriorate in comparison with routine diet consumers. Studies confirmed that these complications are caused by escalating the amount of Lactobacillus, Bifidobacterium, and Prevotella and also reduced the amount of Clostridium in the intestine [9]. However, the role of S. cerevisiae, S. boulardii, Parabacteroides goldsteinii, Akkermansia muciniphila, Enterobacter halii have been elucidated as a new generation of probiotics [9,10].

Antibiotics upregulate the expression of adipose tissue genes and downregulate the immune system pathways as well. These changes can be counted as microbiota dysbiosis through antibiotic administration, which is directly effective in the currency of obesity [11].

2.2. Animal studies

Animal studies stressed that the transfer of normal maternal flora to the fetus occurs in both the prenatal and postnatal periods, which is associated with the metabolic syndrome, fat deposition, and obesity [10,11]. Accumulated bacteria in the maternal lymph nodes are transferred through the placenta to the fetus, and also the vaginal flora are transmitted to the fetus during delivery [5,8]. Besides, the bacteria are also transmitted through lactation. These bacteria can be normal flora or probiotics consumed [5].

Harvesting energy from carbohydrate-rich food mostly occurs in ob/ob mice. Moreover, the maternal abundance of the dominant gut microbiota can influence the development of obesity [12]. Furthermore, transplantation of microbiota to an obesity-resistant germ-free mice resulted in more calorie uptake and obesity [7].

Furthermore, the gut microbiota is responsible for the expression of AMP-activated protein kinase (AMPA) and fasting-induced adipose factor (Fiaf), which both trigger weight gain from foods containing fat and carbohydrate [13]. Both human and animal studies are summarized in Table 1.

3. Role of probiotics in current treatments

To conceive the role of probiotics, human studies reported improvements in lipid profile, in particular, decreased level of total cholesterol, LDL cholesterol, and plasma TG and increased amount of HDL cholesterol and also insulin sensitivity as probiotics consumption’s merits [14]. Also, in a study on DIO mice, Lactobacillus rhamnosus, L. acidophilus, and Bifidobacterium bifidumi were administered to modulate gut microbiota. An improvement in insulin sensitivity and therefore in obesity was resulted through the hypothalamic control of food intake, and insulin and leptin signaling beside equilibrium of the flora [15].

Most of the studies support anti-obesity benefits of some types of probiotics such as Lactobacillus (L. casei strain Shirota (LAB13), L. gasseri, L. rhamnosus, and L. plantarum, among others) and Bifidobacterium (mainly B. infantis, B. longum, and B. breve B3) during 4 to 6 weeks of consumption [16–18]. Also, probiotics such as L. rhamnosus CGMCC1.3724 is beneficial in the prevention of obesity-related problems and showed an anti-obesogenic property [17]. Whereas some other studies reported the same result while using placebos [17], or deleterious consequences from the use of other strains [5].

In another definition, obesity is regarded as a subclinical low-grade inflammation and associates the effects of probiotics with the regulation of cytokines (IL-10, IL-17, and IL-22) and reduction of pro-inflammatory genes [17]. In some in-vitro and in-vivo studies of Lactobacillus acidophilus, suppression of pro-inflammatory cytokines such as IL-6, tumor necrosis factor-a, IL-1b, and IL-17 and also increased amounts of IL-10 and regulatory T cells were resulted [18].

A recent study showed that L. rhamnosus LS-8 and L. crustorum MN047 alleviate the inflammatory response through normalizing mRNA expression levels in obese mice with high fat and high fructose diet (HFFD) [19].

Also, fibroblast growth factor 21 (FGF21) manages the regulation of lipid metabolism and the profitable impact of probiotics (Lactobacillus rhamnosus GG) have been shown to alleviate the metabolic disorder and obesity in both human and mice [20].

To sum up, Lactobacillus and Bifidobacterium species were reported as the genera with the most attractive results of losing weight, but overall use of probiotics in risky populations should be limited, whereas common adverse effects such as heartburn, headache, and diarrhea, may lead to irreparable problems or death [2].

4. Conclusion

Burdensome results of obesity not only cause irreparable problems for the individual but can also cause a financial impact on society; therefore, its prevention and treatment should be of great interest. Due to various adverse effects of medications of obesity, they were removed from the market, and in that case, many animal and human studies shed light on the role of gut microbiota, in particular (Firmicutes and Bacteroidetes) in the development of metabolic diseases and obesity. Consumption of probiotics as an anti-obesity and anti-obesogenic agent, lead to the correction of gut dysbiosis. Several studies demonstrated that Lactobacillus and Bifidobacterium genera are the most potential ones to manage treatment. Further, some reported deleterious effects from the use of other strains. Further studies are needed to specify the exact dosage, duration of administration, and also to characterize side effects before probiotics can be widely prescribed for the prevention and treatment of overweight patients.

5. Expert opinion

Due to the beneficial effect of probiotics in adjusting the gut dysbiosis to rebalance intestine microbiota, the focus of many recent studies have been given to the role of these microorganisms in the management of metabolic diseases and obesity, a serious global concern, which is directly affected by the imbalance of normal flora. Probiotics anti-obesity property has been linked to the following mechanisms: improvement in lipid profile and insulin sensitivity, control of leptin signaling, regulation of cytokines and reduction of pro-inflammatory genes.

In conclusion, animal and human studies showed weight reduction property and many factors described this characterization. Nevertheless, lifestyle interventions, including dietary changes and physical activity, remain the best way to treat overweight patients.

Declaration of interest

The authors have no relevant affiliations or financial involvement with any organization or entity with a financial interest in or financial conflict with the subject matter or materials discussed in the manuscript. This includes employment, consultancies, honoraria, stock ownership or options, expert testimony, grants or patents received or pending, or royalties.

Reviewer disclosures

Peer reviewers on this manuscript have no relevant financial or other relationships to disclose.

Additional information

Funding

This study was not funded.