The gut microbiota and its relationship to diet and obesity: new insights

Obesity develops from a prolonged imbalance of energy intake and energy expenditure. However, the relatively recent discovery that the composition and function of the gut microbiota impacts on obesity has lead to an explosion of interest in what is now a distinct research field. Here, research relating to the links between the gut microbiota, diet and obesity will be reviewed under five major headings: (1) the gut microbiota of lean and obese animals, (2) the composition of the gut microbiota of lean and obese humans, (3) the impact of diet on the gut microbiota, (4) manipulating the gut microbiota and (5) the mechanisms by which the gut microbiota can impact on weight gain.     

Prebiotic fiber modulation of the gut microbiota improves risk factors for obesity and the metabolic syndrome

Prebiotic fibers are non-digestible carbohydrates that promote the growth of beneficial bacteria in the gut. Prebiotic consumption may benefit obesity and associated co-morbidities by improving or normalizing the dysbiosis of the gut microbiota. We evaluated the dose response to a prebiotic diet on the gut microbiota, body composition and obesity associated risk factors in lean and genetically obese rats. Prebiotic fibers increased Firmicutes and decreased Bacteroidetes, a profile often associated with a leaner phenotype. Bifidobacteria and Lactobacillus numbers also increased. Changes in the gut microbiota correlated with energy intake, glucose, insulin, satiety hormones, and hepatic cholesterol and triglyceride accumulation. Here we provide a comprehensive analysis evaluating the results through the lens of the gut microbiota. Salient, new developments impacting the interpretation and significance of our data are discussed. We propose that prebiotic fibers have promise as a safe and cost-effective means of modulating the gut microbiota to promote improved host:bacterial interactions in obesity and insulin resistance. Human clinical trials should be undertaken to confirm these effects.     

Melatonin prevents obesity through modulation of gut microbiota in mice

Excess weight and obesity are severe public health threats worldwide. Recent evidence demonstrates that gut microbiota dysbiosis contributes to obesity and its comorbidities. The body weight‐reducing and energy balancing effects of melatonin have been reported in several studies, but to date, no investigations toward examining whether the beneficial effects of melatonin are associated with gut microbiota have been carried out. In this study, we show that melatonin reduces body weight, liver steatosis, and low‐grade inflammation as well as improving insulin resistance in high fat diet (HFD)‐fed mice. High‐throughput pyrosequencing of the 16S rRNA demonstrated that melatonin treatment significantly changed the composition of the gut microbiota in mice fed an HFD. The richness and diversity of gut microbiota were notably decreased by melatonin. HFD feeding altered 69 operational taxonomic units (OTUs) compare with a normal chow diet (NCD) group, and melatonin supplementation reversed 14 OTUs to the same configuration than those present in the NCD group, thereby impacting various functions, in particular through its ability to decrease the Firmicutes‐to‐Bacteroidetes ratio and increase the abundance of mucin‐degrading bacteria Akkermansia, which is associated with healthy mucosa. Taken together, our results suggest that melatonin may be used as a probiotic agent to reverse HFD‐induced gut microbiota dysbiosis and help us to gain a better understanding of the mechanisms governing the various melatonin beneficial effects.     

Effects of gut microbiota on obesity and atherosclerosis via modulation of inflammation and lipid metabolism

Recent studies have revealed a close relationship between inflammatory and metabolic pathways, and inflammation is now recognized to have a major role in obesity and metabolic diseases such as insulin resistance and atherosclerosis. The human body is home to a large number of distinct microbial communities, with the densest population in the distal gut (the gut microbiota). Bacteria have long been known to activate inflammatory pathways, and recent data demonstrate that the gut microbiota may affect lipid metabolism and function as an environmental factor that influences the development of obesity and related diseases. Here, we review how the gut microbiota may affect metabolic diseases by activating the innate immune system.     

Exposure to air pollutants and the gut microbiota: a potential link between exposure,obesity, and type 2 diabetes

ABSTRACT

Work has shown that increased exposure to air pollutants independently contributes to obesity and type 2 diabetes risk, yet the exact mechanisms underlying these associations have not been fully characterized. The current review summarizes recent findings regarding the impact of inhaled and ingested air pollutants on the gut microbiota. Animal and human studies provide evidence that air pollutants, such as particulate matter, nitrogen oxides, and ozone, have the potential to alter the gut microbiota. Further, studies suggest that such exposure-induced alterations to the gut microbiota may contribute to increased risk for obesity and type 2 diabetes through inflammatory pathways. Future work is needed to fully understand the complex interactions between air pollution, the gut microbiome, and human health. Additionally, advanced sequencing methods for gut microbiome research present unique opportunities to study the underlying pathways that link increased air pollution exposure with obesity and type 2 diabetes risk.     

The metabolic activity of gut microbiota in obese children is increased compared with normal-weight children and exhibits more exhaustive substrate utilization

Objective:

The gut microbiota contribute otherwise impossible metabolic functions to the human host. Shifts in the relative proportions of gut microbial communities in adults have been correlated with intestinal disease and have been associated with obesity. The aim of this study was to elucidate differences in gut microbial compositions and metabolite concentrations of obese versus normal-weight children.

Materials and methods:

Fecal samples were obtained from obese (n=15; mean body mass index (BMI) s.d. score=1.95) and normal-weight (n=15; BMI s.d. score=−0.14) Swiss children aged 8–14 years. Composition and diversity of gut microbiota were analyzed by qPCR and temperature gradient gel electrophoresis (TGGE).

Results:

No significant quantitative differences in gut microbiota communities of obese and normal-weight children were identified. Microbial community profiling by TGGE revealed a high degree of both intra- and intergroup variation. Intergroup comparison of TGGE profiles failed to identify any distinct populations exclusive to either obese or normal-weight children. High-pressure liquid chromatography analysis identified significantly higher (P<0.05) concentrations of short-chain fatty acids (SCFA) butyrate and propionate in obese versus normal-weight children. Significantly lower concentrations of intermediate metabolites were detected in obese children, suggesting exhaustive substrate utilization by obese gut microbiota.

Conclusions:

Our results indicate that a dysbiosis may be involved in the etiology of childhood obesity. In turn, aberrant and overactive metabolic activity within the intestine could dictate survival or loss of individual microbial communities, leading to the altered population ratios previously identified in adult obesity.     

CONSORT-Characteristics and metabolic phenotype of gut microbiota in NAFLD patients

Patients with nonalcoholic fatty liver disease (NAFLD) have symptoms of a gut microbiota disorder with abnormal amino acid and glycolipid metabolism. This study was designed to analyze the characteristics of gut microbiota in patients with NAFLD, predict the gut microbiota phenotype, explore its role in the diagnosis of NAFLD, and establish its significance in disease progression.The characteristics of the gut microbiota in NAFLD patients (n = 28, 45.8 ± 14.2 years, male/female = 18/10) and healthy subjects (n = 20, 49.6 ± 4.8 years, male/female = 14/6) during March–May 2020 were analyzed using 16S rRNA sequencing technology and the phenotypes with large differences were predicted using the Tax4Fun method. The metabolites in the fecal samples of the patients were analyzed using mass spectrometry, and their correlation with different microorganisms was examined. The accuracy of the gut microbiota in diagnosing NAFLD was investigated by receiver operating characteristic curve analysis.We found that the microbial diversity and Bacteroides/Firmicutes (BF) ratio changed significantly (P < .05) in the feces of NAFLD patients. Phenotypic prediction showed that there were significant differences in the phenotypes of amino acid, glucose, and lipid metabolism of gut microbiota in the NAFLD group (P < .05). receiver operating characteristic curve analysis revealed that combination of Bacteroides and the BF ratio resulted in 88% and 100% sensitivity and specificity, respectively, when used for NAFLD diagnosis. Metabolomics and bioinformatics analysis revealed changes in the metabolism of nicotinate, nicotinamide, and pyrimidine; signaling pathways of calcium and oxytocin; pancreatic secretion with metabolites such as uracil, xanthine, and biliverdin; and enzymes such as xanthine dehydrogenase and xanthine oxidase (P < .05).Therefore, the phenotypic changes may be a potential marker for NAFLD and we considered that a combined analysis of Bacteroides and BF ratio had good diagnostic accuracy for NAFLD.     

The therapeutic potential of manipulating gut microbiota in obesity and type 2 diabetes mellitus

Obesity and type 2 diabetes mellitus (T2DM) are attributed to a combination of genetic susceptibility and lifestyle factors. Their increasing prevalence necessitates further studies on modifiable causative factors and novel treatment options. The gut microbiota has emerged as an important contributor to the obesity--and T2DM--epidemic proposed to act by increasing energy harvest from the diet. Although obesity is associated with substantial changes in the composition and metabolic function of the gut microbiota, the pathophysiological processes remain only partly understood. In this review we will describe the development of the adult human microbiome and discuss how the composition of the gut microbiota changes in response to modulating factors. The influence of short-chain fatty acids, bile acids, prebiotics, probiotics, antibiotics and microbial transplantation is discussed from studies using animal and human models. Ultimately, we aim to translate these findings into therapeutic pathways for obesity and T2DM in humans.     

The gut microbiota keeps enteric glial cells on the move; prospective roles of the gut epithelium and immune system

The enteric nervous system (ENS) coordinates the major functions of the gastrointestinal tract. Its development takes place within a constantly changing environment which, after birth, culminates in the establishment of a complex gut microbiota. How such changes affect ENS development and its subsequent function throughout life is an emerging field of study that holds great interest but which is inadequately explored thus far. In this addendum, we discuss our recent findings showing that a component of the ENS, the enteric glial cell network that resides in the gut lamina propria, develops after birth and parallels the evolution of the gut microbiota. Importantly, this network was found to be malleable throughout life by incorporating new cells that arrive from the area of the gut wall in a process of directional movement which was controlled by the lumen gut microbiota. Finally, we postulate on the roles of the intestinal epithelium and the immune system as potential intermediaries between gut microbiota and ENS responses.     

The gut microbiota keeps enteric glial cells on the move; prospective roles of the gut epithelium and immune system

The enteric nervous system (ENS) coordinates the major functions of the gastrointestinal tract. Its development takes place within a constantly changing environment which, after birth, culminates in the establishment of a complex gut microbiota. How such changes affect ENS development and its subsequent function throughout life is an emerging field of study that holds great interest but which is inadequately explored thus far. In this addendum, we discuss our recent findings showing that a component of the ENS, the enteric glial cell network that resides in the gut lamina propria, develops after birth and parallels the evolution of the gut microbiota. Importantly, this network was found to be malleable throughout life by incorporating new cells that arrive from the area of the gut wall in a process of directional movement which was controlled by the lumen gut microbiota. Finally, we postulate on the roles of the intestinal epithelium and the immune system as potential intermediaries between gut microbiota and ENS responses.     

肠道菌群及其代谢物与溃疡性结肠炎的关系

溃疡性结肠炎(ulcerative colitis,UC)是一种慢性非特异性结肠和直肠炎性疾病,属于炎症性肠病(inflammatory bowel disease,IBD)中的一种。病变主要局限于大肠黏膜和黏膜下层,通常涉及直肠和乙状结肠,也可延伸至整个结肠。病程漫长,常反复发作,严重影响患者的生活质量[1]。流行病学调查发现,UC见于任何年龄,但初发以20~30岁多见,男女比例为1.0:1~1.3:1。     

Recent progress on the role of gut microbiota in the pathogenesis of inflammatory bowel disease

In recent years investigations of inflammatory bowel disease (IBD) have advanced rapidly with regard to the relationship between the host immune response and gut microbiota. Patients with IBD have been shown to have an abnormal composition of gut microbiota and host immune dysregulation. Abnormal components of gut microbiota, to which the host mounts aberrant immune responses in genetically vulnerable individuals, appear to play a critical role in the pathogenesis of IBD. Therefore, inappropriate innate and adaptive host immune responses to abnormal components of gut microbiota and their products form the basis of IBD pathogenesis. Modern molecular genetic methods should be utilized to help to illuminate the pathogenetic mechanism of IBD and to develop personalized therapeutic strategies for this disease.     

肠道微生物群组与肠道免疫的关系

人类肠道是一个生态系统,存在大量的微生物。肠道微生物群与肠道天然免疫及获得性免疫之间存在动态的相互作用,影响着肠道免疫系统的形成和功能。当这种相互作用中的一步或多步失效时,自身免疫性疾病和炎症性疾病就会发生。回顾肠道微生物群组与肠道免疫功能的关系,有助于提高微生物对免疫系统失调相关的肠道疾病治疗应用的认识。     

Microbiome‐immune‐metabolic axis in the epidemic of childhood obesity: Evidence and opportunities

Obesity epidemic responsible for increase in diabetes, heart diseases, infections and cancer shows no signs of abating. Obesity in children is also on rise, indicating the urgent need of strategies for prevention and intervention that must begin in early life. While originally posited that obesity results from the simple concept of consuming more calories, or genetics, emerging research suggests that the bacteria living in our gut (gut microbiome) and its interactions with immune cells and metabolic organs including adipose tissues (microbiome‐immune‐metabolic axis) play significant role in obesity development in childhood. Specifically, abnormal changes (dysbiosis) in the gut microbiome, stimulation of inflammatory cytokines, and shifts in the metabolic functions of brown adipose tissue and the browning of white adipose tissue are associated with increased obesity. Many factors from as early as gestation appear to contribute in obesity, such as maternal health, diet, antibiotic use by mother and/or child, and birth and feeding methods. Herein, using evidence from animal and human studies, we discuss how these factors impact microbiome‐immune‐metabolic axis and cause obesity epidemic in children, and describe the gaps in knowledge that are warranted for future research.     

Lingguizhugan decoction attenuates diet-induced obesity and hepatosteatosis via gut microbiota

BACKGROUND Obesity is a major risk factor for a variety of diseases such as diabetes,nonalcoholic fatty liver disease, and cardiovascular diseases. Restricting energy intake, or caloric restriction(CR), can reduce body weight and improve metabolic parameters in overweight or obese patients. We previously found that Lingguizhugan decoction(LZD) in combination with CR can effectively lower plasma lipid levels in patients with metabolic syndrome. However, the mechanism underlying CR and LZD treatment is still unclear.AIM To investigate whether CR and LZD improve metabolic parameters by modulating gut microbiota.METHODS We extracted the water-soluble components out of raw materials and dried as LZD extracts. Eight-week old male C57 BL/6 mice were treated with a 3-d treatment regime that included 24 h-fasting followed by gavage of LZD extracts for 2 consecutive days, followed by a normal diet(ND) ad libitum for 16 wk. To test the effects of gut microbiota on diet-induced obesity, 8-wk old male C57 BL/6 mice received fecal microbiota transplantation(FMT) from CR and LZD-treated mice every 3 d and were fed with high-fat diet(HFD) ad libitum for 16 wk.Control mice received either saline gavage or FMT from ND-fed mice receiving saline gavage as mentioned above. Body weight was monitored bi-weekly. Food consumption of each cage hosting five mice was recorded weekly. To monitor blood glucose, total cholesterol, and total triglycerides, blood samples were collected via submandibular bleeding after 6 h fasting. Oxygen consumption rate was monitored with metabolic cages. Feces were collected, and fecal DNA was extracted. Profiles of gut microbiota were mapped by metagenomic sequencing.RESULTS We found that CR and LZD treatment significantly reduced the body weight of mice fed with ND(28.71 ± 0.29 vs 28.05 ± 0.15, P 0.05), but did not affect plasma total cholesterol or total triglyceride levels. We then transplanted the fecal microbiota collected from CR and LZD-treated mice under ND feeding to HFDfed mice. Intriguingly, transplanting the mice with fecal microbiota from CR and LZD-treated mice potently reduced body weight(44.95 ± 1.02 vs 40.53 ± 0.97, P 0.001). FMT also reduced HFD-induced hepatosteatosis, in addition to improved glycemic control. Mechanistic studies found that FMT increased OCR of the mice and suppressed the expression and protein abundance of lipogenic genes in the liver. Metagenomic analysis revealed that HFD drastically altered the profile of gut microbiota, and FMT modified the profile of the gut microbiota.CONCLUSION Our study suggests that CR and LZD improve metabolic parameters by modulating gut microbiota.     

肠道菌群和心血管疾病的免疫调节

心血管疾病是人类健康的第一杀手,发病率和死亡率逐年增加。数万亿微生物寄居于人类肠道,在心血管疾病及其相关的代谢、免疫反应中发挥着至关重要的作用。先天性和适应性免疫机制都参与了心血管疾病的发生发展,菌群组分和代谢产物可调节巨噬细胞、淋巴细胞等免疫细胞的分化及功能,并通过循环系统影响机体免疫稳态。本文将通过肠道菌群及其代谢产物与免疫系统的相互作用,讨论肠道菌群与心血管疾病发展之间潜在的免疫机制,为预防和治疗心血管疾病提供新思路。     

Feeding the brain and nurturing the mind: Linking nutrition and the gut microbiota to brain development

The human gut contains a microbial community composed of tens of trillions of organisms that normally assemble during the first 2–3 y of postnatal life. We propose that brain development needs to be viewed in the context of the developmental biology of this “microbial organ” and its capacity to metabolize the various diets we consume. We hypothesize that the persistent cognitive abnormalities seen in children with undernutrition are related in part to their persistent gut microbiota immaturity and that specific regions of the brain that normally exhibit persistent juvenile (neotenous) patterns of gene expression, including those critically involved in various higher cognitive functions such as the brain’s default mode network, may be particularly vulnerable to the effects of microbiota immaturity in undernourished children. Furthermore, we postulate that understanding the interrelationships between microbiota and brain metabolism in childhood undernutrition could provide insights about responses to injury seen in adults. We discuss approaches that can be used to test these hypotheses, their ramifications for optimizing nutritional recommendations that promote healthy brain development and function, and the potential societal implications of this area of investigation.