The Human Microbiome, Diet, and Health Workshop Summary (2013) / Chapter Skim
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5 Influence of Diet and Dietary Components on the Microbiome
5 Influence of Diet and Dietary Components on the Microbiome
Pages 81-120
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From page 81... ...
In his exploration of the preventive potential of the human diet, Bruce German focuses his research on the one food that evolved to be preventive: human breast milk. The cost–benefit trade-off associated with human milk is key to under tanding milk's preventive potential, German explained.
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From page 82... ...
Carlito Lebrilla developed a methodology for analyzing glycan complexity in human milk, based on innovative separation technologies and very high-efficiency, high-accuracy mass spectrometry (Ninonuevo et al., 2006)
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From page 83... ...
Yet, there is a plethora of clinical and epidemiological data suggesting that breast-feeding promotes mucosal immune development and protects against many diseases. These data, combined with the fact that human milk contains a variety of bioactive proteins, carbohydrates, and lipids not present in infant formula, raise questions about whether and how the infant gut microbiota differs between breast-fed and formula-fed infants.
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From page 84... ...
Given that necrotizing enterocolitis (NEC) is associated with tissue hypoxia and that human milk has been shown to protect preterm infants from NEC, Donovan speculated that upregulation of EPAS1 in breast-fed infants might be helping those babies' guts to tolerate hypoxic episodes.
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From page 85... ...
Also, it would be interesting to see if addition of any of these to infant formula, in the form of a prebiotic or probiotic, would shift the gut microbiota toward the direction of breast-fed infants. Next, Donovan and her team tested the hypothesis that the integration of infant (host)
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From page 86... ...
D She noted that all of the formula-fed infants were receiving the same formula but that breast milk composition can be highly variable. Using established protocols for evaluating community-wide microbial gene expression in stool samples, the team observed a greater total percentage (i.e., percentage of total 16S ribosomal RNA [rRNA]
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From page 87... ...
Nutrients and bioactive components in human milk directly influence the development of the infant's immune system, actively protect the infant from pathogenic infection, and facilitate establishment of the microbiota, the last of which is required to activate the mucosal immune system. Recent data suggest that HMOs contribute to many of these activities (Donovan et al., 2012)
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From page 88... ...
. Since HMOs are resistant to digestion by the infant and pass into the colon, Donovan described them as the fiber of human milk, a fact that she said hasn't really been appreciated until recently.
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From page 89... ...
. Not only is the resistome accruing more resistance genes, either singly or bundled in multigene cassettes, it also appears to be accumulating networks of preferential horizontal gene transfers, or "cliques" (Skippington and Ragan, 2011)
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From page 90... ...
Eventually, humans can potentially become exposed to those same resistance genes via several routes. One way to represent the resistome and the way it transcends, or extends across, all of these different microbiomes, from farm animals to soil bacteria to the human gastrointestinal (GI)
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From page 91... ...
and an increased prevalence of antibiotic-resistant phenotypes (bottom figure) in food animals fed antibiotic-containing diets ("GPA feeds")
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From page 92... ...
Resistant genes can readily travel from one "bug" to another via horizontal gene transfer, either as naked DNA or on cassettes. Even studying the microbiome may not be enough.
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From page 93... ...
. By "tickling" Toll-like receptors and other receptors and signaling pathways that build host immunity, gut microbes might be keeping the host immune system "finely tuned and fit" and preparing the immune system for new challenges (e.g., antibiotic exposure, changes in diet)
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From page 94... ...
. 10 The TNBS challenge is standard protocol for inducing murine colitis, that is, the mouse equivalent of human inflammatory bowel disease.
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From page 95... ...
reuteri may be promoting the sloughing of Rotavirus-infected cells by altering the actin cytoskeleton and weakening attachments of the basement membrane, thereby increasing epithelial cell migration and turnover. Other Mechanisms of Action In addition to host immunity and intestinal epithelium development, probiotics can also influence human health and disease by enhancing microbiome diversity or, more compellingly, by changing microbiome gene expression.
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From page 96... ...
There is a long list of potential prebiotic candidates, including soybean oligosaccharides, glucooligosaccharides, cyclodextrins, gentiooligosaccharides, oligodextrans, glucorinic acid, pectic oligosaccharides, isomaltooligo saccharides, lactosucrose, xylooligosaccharides, human milk oligo accharides, s mannanoligosaccharides (yeast cell wall) , lactose, resistant starch and derivatives, oligosaccharides from melobiose, N-acetylchitooligosaccharides, polydextrose, sugar alcohols, and konjac glucomannan.
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From page 97... ...
In a study on the effect of resistant starch on fecal microbiota in 10 healthy human volunteers, Martinez et al.
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From page 98... ...
Using quantitative real-time PCR (qRT-PCR) to measure the bifidogenic effects of GalOS, again the researchers found a significant increase in bifidogenic activity among individuals fed 5 or 10 grams of GalOS per day, but not among individuals fed 0 or 2.5 grams per day.
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From page 99... ...
production, intestinal morphology, gut immune modulation, and the GI microbiota itself. Are Prebiotics Effective in Achieving Host Health Benefits?
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From page 100... ...
What they don't know, according to Mary Ellen Sanders, is whether probiotic impacts on the microbiome are directly responsible for the observed human health benefits. Most studies that correlate microbiome changes and human health benefit do not reveal anything about causality.
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From page 101... ...
Sanders provided an overview of demonstrated effects of probiotics on the microbiome and on health and scientific challenges to translating this knowledge into probiotic foods. Impact of Probiotics on the Microbiome There is plentiful evidence of the effects of probiotics on the microbiome, especially intestinal microbiota (Sanders, 2011)
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From page 102... ...
These include acute diarrhea, antibiotic-associated diarrhea, travelers' diarrhea, C difficile infection, lactose digestion, irritable bowel syndrome (IBS)
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From page 103... ...
To be convincing, these more general claims will require demonstrating that multiple strains of the same taxonomic group have the same effect and either that a common mechanism of action among the strains mediates this effect or that different mechanisms of action among the strains result in the same effect. Sanders was hopeful that "there may be a time in this field when enough accumulated data are present that we are able to say that although certain activities are definitely linked to certain strains, others do seem to be more broadly attributable to broader microbiological categories or phylogenetic types." Challenges to Translating Probiotic Science into Probiotic Foods While the plethora of probiotic products on the market seems to suggest a lack of any barriers to the development of probiotic foods, in fact there are many scientific, regulatory, technological, and marketing challenges.
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From page 104... ...
An underpowered study providing no evidence of an effect is very different from a sufficiently powered study providing evidence of no effect. Sanders said, "We need to be able to distinguish that and possibly quit running underpowered studies." In addition to these scientific challenges, Sanders suggested that new regulatory challenges may end up discouraging future probiotic research.
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From page 105... ...
Many studies have shown that probiotic bacteria lose their activity over time if they are placed in foods that have not been correctly designed to accommodate those bacteria, according to David Julian McClements. There has been a dramatic increase in probiotic viability studies over the past decade, with many studies showing appreciable reductions in probiotic viability during food storage or during transit through the human GI tract.
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From page 106... ...
Plus, food products encounter a series of
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From page 107... ...
Unlike dried encapsulation systems, they do not fall apart upon exposure to the human body and can be designed to maintain their viability until they reach a specific region of the GI tract. Controlling probiotic viability is a challenge.
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From page 108... ...
Viability is influenced by different characteristics of encapsulation systems: particle size -- larger particles are usually more stable during transit through the GI tract; composition -- the digestibility of the matrix components determines their response; nutritional profile -- the type of nutrients present within a matrix may influence probiotic viability; physical state -- solid particles are often more stable than liquid ones; permeability -- the pore size of matrices can be changed so that digestive enzymes, bile salts, and other stressors cannot access the probiotic; and environmental responsiveness (e.g., microencapsulated probiotics can be designed to swell or shrink under different pH conditions or ionic strengths)
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From page 109... ...
The food we eat is also the major source of growth for our gut microbiota and thereby may be an effective way to steer its composition and activity. The question is, How can we 15 This section summarizes the presentation of Johan van Hylckama Vlieg.
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From page 110... ...
Or, as van Hylckama Vlieg expressed, "Science provides increased rationale for functional food concepts using pre- and probiotics that bring a clear health benefit to consumers." Leveraging the Microbiome for Health In fact, humans have been leveraging the microbiome for a long time, initially through animal husbandry and consumption of fermented foods and moving toward science-based evidence for dietary intake. Fermented foods are important constituents of the human diet worldwide, and use of these foods dates back approximately 10,000 years (Evershed et al., 2008)
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From page 111... ...
The researchers showed "very elegantly," according to van Hylckama Vlieg, that the newly altered intestinal environment in FMP-fed mice inhibits growth of colitogenic bacteria. Research on the impact of FMPs on TRUC mouse microbiome and host health is ongoing.
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From page 112... ...
intervention. For example, as summarized in this chapter, Johan van Hylckama Vlieg mentioned research results demonstrating that Activia does not cause any major perturbation of the microbiota but does trigger distinct transcriptomic responses related to the metabolic activity of Bifidobacterium animalis.
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From page 113... ...
The value of the discovery of histamine as a microbially produced molecule that impacts host immunity isn't the histamine itself. Rather, its value is that "it has pointed us in a whole new direction -- to look at amino acid conversions." Are other amino acids being converted by microbes?
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From page 114... ...
If a study is too underpowered to provide any evidence of an effect, then what is the value of that study? "If you really want to move this field forward," she said, "you really have to start considering your study design." In response, Johan van Hylckama Vlieg remarked that many small studies, such as the twin study that he mentioned, are intended to be exploratory and hypothesis-generating.
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From page 115... ...
Huber, J van Hylckama Vlieg, A
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From page 116... ...
2012. Bifidobacteria isolated from infants and cultured on human milk oligosaccharides af fect intestinal epithelial function.
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From page 117... ...
2010. Consumption of human milk oligosaccharides by gut-related microbes.
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From page 118... ...
2006. A strategy for annotating the human milk glycome.
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From page 119... ...
E van Hylckama Vlieg, S
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