noun_Search_345985 Created with Sketch.
noun_Search_345985 Created with Sketch.
Visit the Lifestyle Section

The latest from The Paleo Diet®, just for you.

Hot topics, new recipes, and science

The Wheat Series Part 3: Setting Off the Bacterial Alarm Bells – With or Without the Bacteria

By Trevor Connor, M.S., CEO
June 16, 2015

Did you miss The Wheat Series Part 1: Wheat and the Immune System?Read it HERE
你错过了小麦系列第2部分:对肠道健康打开障碍吗?Read it HERE

这是一场在数百万年发型的战斗。病毒,细菌和各种各样的病原体寻找一个漂亮的温暖的家园已经进化了越来越复杂的技术来逃避我们的技术immune systems。In response, our immune systems developed an array of specialized cells to launch remarkably targeted attacks at these unwanted invaders.

In the face of this cellular army, pathogens discovered one of their best weapons is a microscopic form of hide-and-seek.

Viruses mimic our bodies so immune cells pass them by.1, 2Meningitis hangs out in the nervous system where immune cells dare not go, and HIV takes up home in immune cells themselves – after, of course, dismantling a few defenses.

These are all ways of telling the immune system “keep moving, nothing to see here.”

But what would happen if instead of looking for a good hiding place, an invader actually tried to set off the immune system alarm bells? More importantly, why would an invader want to do that?

Well, imagine you’re a plant. When some hungry animal looks at you and says “lunch” you can’t really run away. Nor can you fight back. So what do you do?

You make sure that after the animal has its meal, it is sick enough to think twice about ever touching one of your brethren.


InPart Oneof this series on wheat, I talked about how the normally sluggish digestive immune system can become inappropriately inflamed and lead to disease. Three things can cause this:肠道渗透率(泄漏肠道); chronic or too high a bacterial load; and dietary antigens.

Wheat has the unique distinction of influencing all three.

The first, intestinal permeability, is promoted by wheat through the release of zonulin.3.-5We covered that inPart Two

Let’s get to Part Three – chronic or too high a bacterial load.

Of course, you’ve probably already realized that wheat is not bacteria. True. But the same way viruses mimic our bodies, wheat has evolved ways to “mimic” bacteria. All with the purpose of setting off the immune system alarm bells – whether the bacteria is there or not.


Our bodies actually like bacteria.

At least when they stay where they belong - in thegut.6-9In fact, inPart One,我们谈到了我们的消化免疫系统中的大部分时间,以便我们养活这种细菌。7,9-11

It’s when the bacteria - especially the less friendly types such as gram negative bacteria - get into our bodies that the immune system takes action. As a result, our immune cells have developed critical tools for the sole purpose of hunting down and identifying bacteria inside the body.


Antigen presenting cells (APCs) hunt down bacteria using two receptors for LPS called TLR-4 and CD14.12, 13When LPS binds TLR-4 and CD14, the immune system alarm bells go off.

The diagram below shows the basics of this sophisticated alarm system,14but the end result is simple. The immune system spins up andinflammationensues.

The Wheat Series Part 3: Setting Off the Bacterial Alarm Bells – With or Without the Bacteria | The Paleo Diet

小麦 - 伟大的细菌模仿者

字幕实际上仅部分准确。更好的描述可能是“小麦– the boy who cried bacterial wolf.”

The problem is our bodies never learn to ignore this particular boy.

Wheat has developed a variety of sophisticated techniques for activating the LPS response. But in some cases, it does it differently from LPS, bypassing key regulatory steps such as CD14 which would otherwise prevent inflammation in places we don’t want it.6,10



Part Twogives an in depth description of how wheat opens up the消化道障碍并允许在我们的肠道中进入​​我们的身体。这包括我们的肠道细菌。15

The Wheat Series Part 3: Setting Off the Bacterial Alarm Bells – With or Without the Bacteria | The Paleo Diet

In other words, wheat actually lets the wolf into the chicken coop and then cries wolf.


Wheat contains its own LPS-like molecule, sometimes called LPSw, that has similar effects but admittedly isn’t as potent as the real thing.16,17在对小鼠的一项研究中,LPSW能够促进细菌免疫反应。17


(No It’s Not a Computer Company)

At thebarrier of our gut是一种特殊类型的免疫细胞,称为树突细胞。不断对消化道进行抽样,它们是免疫系统的开/关开关。18Think of them as Paul Revere riding back to the immune system yelling “the bacteria are coming!”

Wheat contains molecules that very potently activates dendritic cells called α-Amylase/Trypsin Inhibitors (ATIs).19They act through TLR-4 on the dendrites. And sorry to those of you who love to say you’re “gluten-free” – ATIs, which exist in many grains, are found in a different part than gluten.

ATI的负责呼吁较长的病情Baker’s Asthmanamed so because it was common among people who worked with flour.20


TLR-4 and CD14 are not strongly expressed in the gut immune system making it hard to sound the bacterial alarm in the gut.21-23In an area of the body that’s exposed to bacteria thousands of times each day, an inflammatory response isn’t something we want.21, 22


The ways wheat does it gets complex. We’ll just touch on them.

First, in several studies, small amounts of gluten were able to flip the dendritic cell’s “on switch” in mice and start an inflammatory response without touching TLR-4.24, 25

Another molecule in wheat (there’s a lot) called wheat germ agglutinin (WGA) can bind and pass right through the gut barrier to interact with immune cells on the other side. WGA then promotes a highly inflammatory response26, 27including turning dendritic cells on.

Finally, remember all those antigen presenting cells in the gut that avoid sounding the bacterial alarm bells by simply not expressing CD14?格里亚丁P.romotes something called IL-15 which is highly effective at activating APCs that don’t express CD14.28-33

And of a variety of foods tested, gliadin was the only one able to so effectively activate these cells.3.3.


That’s a lot of science and frankly we only just skimmed the surface. So here’s the point – wheat is amazingly effective at activating the bacterial defence mechanisms of our immune cells.


So what happens when our bodies mount a defense against bacteria that isn’t there? The answer to that question is the focus of the final part to this series. But the short answer is it creates a constant state of inflammation as long as we continue to eat wheat.3.4.那3.5

Recent research is now associating a state of constant inflammation with the onset of nearly all major chronic diseases3.6includingheart disease3.7Alzheimer’s disease3.8.diabetes3.9癌症40,41and overall morbidity.4.2

But the question remains does the inflammation that results from wheat inappropriately setting off the bacterial alarms also contribute to these conditions?

That’s a question we’ll hope to delve into in the next two parts. But fortunately, by eating a wheat-free史前饮食那it’s a question you may never have to worry about.

Read The Wheat Series Part 4: Home Invasion HERE


[1]Alcami, A.,Viral mimicry of cytokines, chemokines and their receptors.Nat Rev Immunol, 2003.3.(1):p。3.6-50.

[2]Amara, A. and J. Mercer,Viral apoptotic mimicry.Nat Rev Microbiol, 2015.

[3]Lammers, K.M., et al.,胶质蛋白通过与趋化因子受体CXCR3结合而诱导肠道渗透性和Zonulin释放的增加。胃肠学,2008年。135(1):p。194-204 e3.

[4]Drago, S., et al.,格里亚丁那zonulin and gut permeability: Effects on celiac and non-celiac intestinal mucosa and intestinal cell lines.Scand J Gastroenterol, 2006.4.1(4):p。4.08-19.

[5]Visser, J., et al.,紧密的交叉点,肠道渗透性和自身免疫:乳糜泻和1型糖尿病范例。Ann N Y Acad Sci, 2009.1165.:p。195-205.

[6]Ohnmacht, C., et al.,肠道微生物群,免疫系统的进化tem and the bad reputation of pro-inflammatory immunity.Cell Microbiol, 2011.13(5):p。653-9。

[7]McFall-Ngai, M.,Adaptive immunity: care for the community.Nature, 2007.4.4.5(7124): p. 153.

[8]Ivanov, II, et al.,Induction of intestinal Th17 cells by segmented filamentous bacteria.Cell, 2009.139(3): p. 485-98.

[9]Cao, A.T., et al.,Th17细胞上调聚合物Ig受体和肠IgA,并有助于肠道稳态。J免疫素,2012年。189(9):p。4666-73。

[10]史密斯,p.d.等。,肠道巨噬细胞和对微生物侵占的反应。Mucosal Immunol, 2011.4.(1):p。31-42。

[11]Arrieta, M.-C. and B.B. Finlay,共数微生物群驱动免疫稳态。Frontiers in Immunology, 2012.3.

[12]Kawai,T.等人。,Lipopolysaccharide stimulates the MyD88-independent pathway and results in activation of IFN-regulatory factor 3 and the expression of a subset of lipopolysaccharide-inducible genes.J免疫素,2001年。167(10): p. 5887-94.

[13]Perera, P.Y., et al.,CD11b/CD18 acts in concert with CD14 and Toll-like receptor (TLR) 4 to elicit full lipopolysaccharide and taxol-inducible gene expression.J免疫素,2001年。166(1):p。574-81.

[14]Buer, J. and R. Balling,小鼠,微生物和感染模型。NAT Rev Genet,2003。4.(3): p. 195-205.

[15]Fasano, A.,Zonulin及其对肠道屏障功能的调节:炎症,自身免疫和癌症的生物门。Physiol Rev, 2011.91(1):p。151-75。

[16]Yamazaki, K., J.A. Murray, and H. Kita,Innate immunomodulatory effects of cereal grains through induction of IL-10.Journal of Allergy and Clinical Immunology, 2008.121(1):p。172-178.

[17]Nishizawa, T., et al.,家ostasis as regulated by activated macrophage. I. Lipopolysaccharide (LPS) from wheat flour: isolation, purification and some biological activities.Chem Pharm Bull (Tokyo), 1992.4.0(2):p。479-83。

[18]Williamson, E., G.M. Westrich, and J.L. Viney,Modulating dendritic cells to optimize mucosal immunization protocols.J Immunol,1999。163(7): p. 3668-75.

[19]Junker, Y., et al.,小麦淀粉酶胰蛋白酶抑制剂通过激活Toll样受体4驱动肠炎。J Exp Med, 2012.209(13): p. 2395-408.

[20]Sapone, A., et al.,相关蛋白质相关疾病的光谱:关于新命名和分类的共识。BMC Med,2012。10:p。13。

[21]Kamada, N., et al.,独特的CD14肠巨噬细胞体积ribute to the pathogenesis of Crohn disease via IL-23/IFN-gamma axis.J Clin Invest, 2008.118(6):p。2269-80.

[22]Nagler-Anderson, C.,Tolerance and immunity in the intestinal immune system.Critical Reviews in Immunology, 2000.20(2):p。103-120.

[23]Smythies, L.E., et al.,Human intestinal macrophages display profound inflammatory anergy despite avid phagocytic and bacteriocidal activity.J Clin Invest, 2005.115(1):p。66-75.

[24]Palova-Jelinkova, L., et al.,格里亚丁fragments induce phenotypic and functional maturation of human dendritic cells.J Immunol, 2005.175(10): p. 7038-45.

[25]Nikulina, M., et al.,Wheat gluten causes dendritic cell maturation and chemokine secretion.J免疫素,2004年。173(3): p. 1925-33.

[26]达拉佩勒格里纳,C.等。,Effects of wheat germ agglutinin on human gastrointestinal epithelium: insights from an experimental model of immune/epithelial cell interaction.Toxicol Appl Pharmacol,2009。237(2):p。146-53.

[27]Gabor, F., M. Stangl, and M. Wirth,Lectin-mediated bioadhesion: binding characteristics of plant lectins on the enterocyte-like cell lines Caco-2, HT-29 and HCT-8.J Control Release, 1998.55(2-3):p。131-42。

[28]Harris, K.M., A. Fasano, and D.L. Mann,与IL-15支持Th17单核细胞分化nd Th1 responses to wheat gliadin: implications for celiac disease.Clin Immunol, 2010.135(3): p. 430-9.

[29]Bernardo, D., et al.,Is gliadin really safe for non-coeliac individuals? Production of interleukin 15 in biopsy culture from non-coeliac individuals challenged with gliadin peptides.Gut, 2007.56(6):p。8.8.9-890.

[30]Jelinkova, L., et al.,格里亚丁stimulates human monocytes to production of IL-8 and TNF-alpha through a mechanism involving NF-kappaB.FEBS Lett, 2004.571(1-3): p. 81-5.

[31]Palova-Jelinkova, L., et al.,Pepsin digest of wheat gliadin fraction increases production of IL-1beta via TLR4/MyD88/TRIF/MAPK/NF-kappaB signaling pathway and an NLRP3 inflammasome activation.PLoS One, 2013.8.(4):p。E62426。

[32]Thomas, K.E., et al.,格里亚丁stimulation of murine macrophage inflammatory gene expression and intestinal permeability are MyD88-dependent: role of the innate immune response in Celiac disease.J Immunol, 2006.176(4):p。2512-21.

[33]Tuckova,L.等人,Activation of macrophages by gliadin fragments: isolation and characterization of active peptide.J Leukoc Biol, 2002.71(4):p。625-31.

[34]Nilsen,e.m.等。,外周血T细胞的麸质激活诱导腹腔患者和对照中的Th0样细胞因子图案。Clin Exp Immunol, 1996.103(2):p。295-303。

[35]Antvorskov, J.C., et al.,Dietary gluten alters the balance of pro-inflammatory and anti-inflammatory cytokines in T cells of BALB/c mice.免疫学,2013年。138(1):p。23-33.

[36]Hotamisligil,G.S.,炎症和代谢障碍。Nature, 2006.4.4.4.(7121): p. 860-867.

[37]Libby, P., P.M. Ridker, and A. Maseri,炎症和动脉粥样硬化。Circulation, 2002.105(9):p。1135-1143。

[38]Akiyama,H.等。,Inflammation and Alzheimer's disease.Neurobiology of Aging, 2000.21(3): p. 383-421.

[39]Xu, H.Y., et al.,Chronic inflammation in fat plays a crucial role in the development of obesity-related insulin resistance.Journal of Clinical Investigation, 2003.112(12): p. 1821-1830.

[40]Greennikov,S.I.,F.R.Greten和M. Karin,Immunity, Inflammation, and Cancer.Cell, 2010.140(6):p。883-899。

[41]Coussens, L.M. and Z. Werb,Inflammation and cancer.自然,2002年。4.20(6917): p. 860-867.

[42]Krabbe,K.s.,M. Pedersen和H. Bruunsgaard,老年人的炎症介质。Exp Gerontol, 2004.3.9(5):p。687-99。

Even More Articles For You

1400-Year-Old Bread: Exciting Discovery, but Is It Game Changing?
Does the discovery of 14,000-year-old bread have implications for the Paleo diet? We parse out the potential impact of this discovery in today's post!
By Trevor Connor
Ann Dredge has been called “probably the first New Zealander to come back from end-stage Alzheimer’s. How did she do it? Read this article to find out!
By David Whiteside
I am often asked whether honey, a common staple in contemporary Paleo Diets, is beneficial. While it's better than table sugar it’s still mostly fructose.
By Casey Thaler
Paleo Leadership
Trevor Connor
Trevor Connor

Loren Cordain博士的最终研究生,Trevor Connor,M,M.S.带来了十多年的营养和生理学专业知识,以刺激新的Paleo饮食团队。

Mark J Smith.
Dr. Mark Smith

Paleo运动的原始成员之一,Mark J. Smith,Ph.D.,普遍为Paleo营养的益处花了近30年。

Nell Stephenson
Nell Stephenson

铁man athlete, mom, author, and nutrition blogger Nell Stephenson has been an influential member of the Paleo movement for over a decade.

Loren Cordain
Dr. Loren Cordain

As a professor at Colorado State University, Dr. Loren Cordain developed The Paleo Diet® through decades of research and collaboration with fellow scientists around the world.