抗原变异可使得多种致病微生物易于逃避宿主免疫应答。表达在感染红细胞表面的恶性疟原虫红细胞表面蛋白1（PfPMP1）与感染红细胞、内皮细胞、树突状细胞以及胎盘的单个或多个受体作用，在黏附及免疫逃避中起关键的作用。每个单倍体基因组var基因家族编码约60种成员，通过启动转录不同的var基因变异体为抗原变异提供了分子基础。

疟原虫var基因转换速率变化导致抗原变异[英]／Paul H, Robert P, Christodoulou Z, et al//Proc Natl Acad Sci U S A

The worldwide obesity epidemic is stimulating efforts to identify host and environmental factors that affect energy balance. Comparisons of the distal gut microbiota of genetically obese mice and their lean littermates, as well as those of obese and lean human volunteers have revealed that obesity is associated with changes in the relative abundance of the two dominant bacterial divisions, the Bacteroidetes and the Firmicutes. Here we demonstrate through metagenomic and biochemical analyses that these changes affect the metabolic potential of the mouse gut microbiota. Our results indicate that the obese microbiome has an increased capacity to harvest energy from the diet. Furthermore, this trait is transmissible: colonization of germ-free mice with an 'obese microbiota' results in a significantly greater increase in total body fat than colonization with a 'lean microbiota'. These results identify the gut microbiota as an additional contributing factor to the pathophysiology of obesity.

An obesity-associated gut microbiome with increased capacity for energy harvest

This study describes and validates a new method for metagenomic biomarker discovery by way of class comparison, tests of biological consistency and effect size estimation. This addresses the challenge of finding organisms, genes, or pathways that consistently explain the differences between two or more microbial communities, which is a central problem to the study of metagenomics. We extensively validate our method on several microbiomes and a convenient online interface for the method is provided at http://huttenhower.sph.harvard.edu/lefse/.

/pdf/metagenomic-biomarker-discovery-and-explanation-x530ilzkca.pdf

Metagenomic biomarker discovery and explanation

The human endogenous intestinal microflora is an essential “organ” in providing nourishment, regulating epithelial development, and instructing innate immunity; yet, surprisingly, basic features remain poorly described. We examined 13,355 prokaryotic ribosomal RNA gene sequences from multiple colonic mucosal sites and feces of healthy subjects to improve our understanding of gut microbial diversity. A majority of the bacterial sequences corresponded to uncultivated species and novel microorganisms. We discovered significant intersubject variability and differences between stool and mucosa community composition. Characterization of this immensely diverse ecosystem is the first step in elucidating its role in health and disease.

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Diversity of the human intestinal microbial flora.

Long-term dietary intake influences the structure and activity of the trillions of microorganisms residing in the human gut, but it remains unclear how rapidly and reproducibly the human gut microbiome responds to short-term macronutrient change. Here we show that the short-term consumption of diets composed entirely of animal or plant products alters microbial community structure and overwhelms inter-individual differences in microbial gene expression. The animal-based diet increased the abundance of bile-tolerant microorganisms (Alistipes, Bilophila and Bacteroides) and decreased the levels of Firmicutes that metabolize dietary plant polysaccharides (Roseburia, Eubacterium rectale and Ruminococcus bromii). Microbial activity mirrored differences between herbivorous and carnivorous mammals, reflecting trade-offs between carbohydrate and protein fermentation. Foodborne microbes from both diets transiently colonized the gut, including bacteria, fungi and even viruses. Finally, increases in the abundance and activity of Bilophila wadsworthia on the animal-based diet support a link between dietary fat, bile acids and the outgrowth of microorganisms capable of triggering inflammatory bowel disease. In concert, these results demonstrate that the gut microbiome can rapidly respond to altered diet, potentially facilitating the diversity of human dietary lifestyles.

/pdf/diet-rapidly-and-reproducibly-alters-the-human-gut-drvn0pi8vp.pdf

Diet rapidly and reproducibly alters the human gut microbiome

The microbial communities that colonize different regions of the human gut influence many aspects of health. In the healthy state, they contribute nutrients and energy to the host via the fermentation of nondigestible dietary components in the large intestine, and a balance is maintained with the host's metabolism and immune system. Negative consequences, however, can include acting as sources of inflammation and infection, involvement in gastrointestinal diseases, and possible contributions to diabetes mellitus and obesity. Major progress has been made in defining some of the dominant members of the microbial community in the healthy large intestine, and in identifying their roles in gut metabolism. Furthermore, it has become clear that diet can have a major influence on microbial community composition both in the short and long term, which should open up new possibilities for health manipulation via diet. Achieving better definition of those dominant commensal bacteria, community profiles and system characteristics that produce stable gut communities beneficial to health is important. The extent of interindividual variation in microbiota composition within the population has also become apparent, and probably influences individual responses to drug administration and dietary manipulation. This Review considers the complex interplay between the gut microbiota, diet and health.

The role of the gut microbiota in nutrition and health

Bacteria that colonize the mammalian intestine collectively possess a far larger repertoire of degradative enzymes and metabolic capabilities than their hosts. Microbial fermentation of complex non...

https://www.tandfonline.com/doi/pdf/10.4161/gmic.19897

Microbial degradation of complex carbohydrates in the gut

The populations of dominant species within the human colonic microbiota can potentially be modified by dietary intake with consequences for health. Here we examined the influence of precisely controlled diets in 14 overweight men. Volunteers were provided successively with a control diet, diets high in resistant starch (RS) or non-starch polysaccharides (NSPs) and a reduced carbohydrate weight loss (WL) diet, over 10 weeks. Analysis of 16S rRNA sequences in stool samples of six volunteers detected 320 phylotypes (defined at >98% identity) of which 26, including 19 cultured species, each accounted for >1% of sequences. Although samples clustered more strongly by individual than by diet, time courses obtained by targeted qPCR revealed that 'blooms' in specific bacterial groups occurred rapidly after a dietary change. These were rapidly reversed by the subsequent diet. Relatives of Ruminococcus bromii (R-ruminococci) increased in most volunteers on the RS diet, accounting for a mean of 17% of total bacteria compared with 3.8% on the NSP diet, whereas the uncultured Oscillibacter group increased on the RS and WL diets. Relatives of Eubacterium rectale increased on RS (to mean 10.1%) but decreased, along with Collinsella aerofaciens, on WL. Inter-individual variation was marked, however, with >60% of RS remaining unfermented in two volunteers on the RS diet, compared to <4% in the other 12 volunteers; these two individuals also showed low numbers of R-ruminococci (<1%). Dietary non-digestible carbohydrate can produce marked changes in the gut microbiota, but these depend on the initial composition of an individual's gut microbiota.

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Dominant and diet-responsive groups of bacteria within the human colonic microbiota.

Butyrate arising from microbial fermentation is important for the energy metabolism and normal development of colonic epithelial cells and has a mainly protective role in relation to colonic disease. While certain dietary substrates such as resistant starch appear to be butyrogenic in the colon, it is not known to what extent these stimulate butyrate production directly, e.g. by promoting amylolytic species, or indirectly, e.g. through cross-feeding of fermentation products. Cultural and molecular studies indicate that the most numerous butyrate-producing bacteria found in human faeces are highly oxygen-sensitive anaerobes belonging to the Clostridial clusters IV and XIVa. These include many previously undescribed species related to Eubacterium, Roseburia, Faecalibacterium and Coprococcus whose distribution and metabolic characteristics are under investigation. A better understanding of the microbial ecology of colonic butyrate-producing bacteria will help to explain the influence of diet upon butyrate supply, and to suggest new approaches for optimising microbial activity in the large intestine.

The microbiology of butyrate formation in the human colon.

It has been proposed that the development of obesity in humans is influenced by the relative proportions of the two major phyla of bacteria (Bacteroidetes and Firmicutes) present in the large intestine. To examine the relationships between body mass index, weight loss and the major bacterial groups detected in fecal samples. Major groups of fecal bacteria were monitored using fluorescent in situ hybridization (FISH) in obese and non-obese subjects under conditions of weight maintenance, and in obese male volunteers undergoing weight loss on two different reduced carbohydrate weight-loss diets given successively for 4 weeks each. We detected no difference between obese and non-obese individuals in the proportion of Bacteroidetes measured in fecal samples, and no significant change in the percentage of Bacteroidetes in feces from obese subjects on weight loss diets. Significant diet-dependent reductions in a group of butyrate-producing Firmicutes were, however, detected in fecal samples from obese subjects on weight loss diets. Diets designed to achieve weight loss in obese subjects can significantly alter the species composition of the gut microbiota, but we find no evidence that the proportions of Bacteroidetes and Firmicutes among fecal bacteria have a function in human obesity.

Sylvia H. Duncan

Papers

The role of the gut microbiota in nutrition and health

Microbial degradation of complex carbohydrates in the gut

Dominant and diet-responsive groups of bacteria within the human colonic microbiota.

The microbiology of butyrate formation in the human colon.

Human colonic microbiota associated with diet, obesity and weight loss.