Understanding the Holobiont: How Microbial Metabolites Affect Human Health and Shape the Immune System

In the paper

“administration of synthetic NR1I2 agonists exerts protective effects in mouse models of colitis (Dou et al., 2013; Garg et al., 2016; Shah et al., 2007; Terc et al., 2014; Venkatesh et al., 2014).”

What the sources say

• Partly supported

  The Abstract and Discussion report that chrysin activated PXR (NR1I2) and reduced chemically induced colitis in mice. But the Introduction identifies chrysin as a naturally occurring flavonoid, not a synthetic agonist; this study therefore does not support the claim's synthetic-agent qualifier. (LLM, conf=0.88)

  cites Dou et al., 2013 sourceExperimental — accuracy not yet measured
• Supported

  The Experimental Colitis section identifies PCN as a mouse-specific PXR (NR1I2) agonist administered to mice with DSS-induced colitis. The Results report that PCN significantly reduced colonic damage, thickening, and barrier dysfunction in that model. This paper therefore supports the protective-effect claim as one example among the sentence’s multiple citations. (LLM, conf=0.90)

  cites Garg et al., 2016 source
• Not checked yetcites Shah et al., 2007 source

In the paper

“it was demonstrated that expression of IL-22 requires the AhR (Martin et al., 2009; Veldhoen et al., 2008).”

What the sources say

• Not checked yetcites Martin et al., 2009 source
• Partly supported

  The Abstract section (page not indicated) reports that AhR-deficient CD4 T cells differentiated into TH17 cells but lacked IL-22 expression; it also reports that AhR reconstitution restored IL-22 expression under TH17 conditions. This supports a requirement for AhR in the TH17-cell conditions studied, but not the unqualified claim that all IL-22 expression requires AhR. (LLM, conf=0.85)

  cites Veldhoen et al., 2008 sourceExperimental — accuracy not yet measured

In the paper

“Nr1h4−/− mice also develop spontaneous hepatic inflammation and liver tumors (I. Kim et al., 2007; Yang et al., 2007).”

What the sources say

• Supported

  The Discussion (p. 3) describes sustained chronic inflammation in Fxr-null mice and reports liver tumors in 38% of the mice at 12 months. The Introduction (p. 1) also says the mice spontaneously developed liver lesions, adenomas, and carcinomas. (LLM, conf=0.92)

  cites I. Kim et al., 2007 source
• Not checked yetcites Yang et al., 2007 source

In the paper

“This observation also holds true when the microbiota from obese or lean humans is transferred to germ-free mice (Ridaura et al., 2013; Tremaroli et al., 2015).”

What the sources say

• Not checked yetcites Ridaura et al., 2013 source
• Not checked yetcites Tremaroli et al., 2015 source

In the paper

“When a germ-free mouse receives the microbiota of an obese individual, the ability to effectively utilize high-caloric nutrients is transferred along with it, resulting in obesity of the recipient.”

In the paper

“The composition of the microbiome differs between obese and lean individuals in humans and in animal models: obesity is associated with a relative increase in Firmicutes at the expense of Bacteroidetes (Ley et al., 2005; 2006).”

What the sources say

• ?Not matched

  Couldn’t be matched to a paper in Crossref, so it can’t be checked.

  cites Ley et al., 2005; 2006

In the paper

“In addition to changes in energy metabolism, obesity has also been linked to a deterioration of the intestinal mucosa and resultant chronic, systemic inflammation, analogous to type 2 diabetes (see below) (Boutagy et al., 2016).”

What the sources say

• Not checked yetcites Boutagy et al., 2016 source

In the paper

“They found that l-carnitine and its metabolite γ-butyrobetaine also promoted atherosclerosis in mice, and that elevated plasma levels of l-carnitine were associated with increased risk of cardiovascular disease in individuals with elevated TMAO plasma levels (Koeth et al., 2013; 2014).”

What the sources say

• ?Not matched

  Couldn’t be matched to a paper in Crossref, so it can’t be checked.

  cites Koeth et al., 2013; 2014

In the paper

“Elimination of the gut microbiota by treatment with antibiotics negated the choline-induced exacerbation of atherosclerosis, confirming the importance of the gut microbiome in this process (Z. Wang et al., 2011).”

What the sources say

• Not checked yetcites Z. Wang et al., 2011

In the paper

“Hazen and colleagues separately investigated l-carnitine, an amino acid found in red meat that is also converted to TMAO after processing by gut bacteria.”

What the sources say

• ?Not matched

  Couldn’t be matched to a paper in Crossref, so it can’t be checked.

  cites Koeth et al., 2013; 2014

In the paper

“First, the gut microbiota associated with T2D produces lower levels of short-chain fatty acids (SCFAs, discussed in detail below), which have been shown in vitro and in vivo to support the integrity of the intestinal mucosa in a variety of ways (Fukuda et al., 2011; Gaudier et al., 2004; Macia et al., 2015; Willemsen et al., 2003; Wrzosek et al., 2013).”

In the paper

“Consistent with this finding, supplementing food with choline or TMAO promoted atherosclerosis in mice.”

What the sources say

• Not checked yetcites Z. Wang et al., 2011

In the paper

“Bacteria of the gut microbiota process dietary phosphatidylcholine to yield trimethylamine (TMA), which is absorbed by the host and oxidized in the liver to trimethylamine N-oxide (TMAO).”

In the paper

“Host genetic variation has been shown to be associated with variation in the microbiome composition, but genome-wide approaches to identify individual genes and their role in shaping the microbiome are only beginning to emerge (Blekhman et al., 2015; Spor et al., 2011).”

What the sources say

• Not checked yetcites Blekhman et al., 2015 source
• Not checked yetcites Spor et al., 2011 source

In the paper

“which have been shown in vitro and in vivo to support the integrity of the intestinal mucosa in a variety of ways (Fukuda et al., 2011; Gaudier et al., 2004; Macia et al., 2015; Willemsen et al., 2003; Wrzosek et al., 2013).”

What the sources say

• Not checked yetcites Fukuda et al., 2011 source
• Not checked yetcites Gaudier et al., 2004 source
• Not checked yetcites Macia et al., 2015 source

In the paper

“A seminal study by Hazen and colleagues discovered that plasma levels of TMAO and its precursors choline and betaine predicted the risk of cardiovascular disease in humans, thus identifying a novel connection between the microbiome and metabolic health.”

What the sources say

• Not checked yetcites Z. Wang et al., 2011

In the paper

“Correspondingly, patients suffering from T2D have been reported to exhibit increased plasma levels of LPS (Creely et al., 2007).”

What the sources say

• Not checked yetcites Creely et al., 2007 source

In the paper

“Recently, Plovier et al. reported that much of this effect could be replicated by administration of a membrane protein purified from A. muciniphila, suggesting the appealing possibility of a novel therapeutic application (Plovier et al., 2017).”

What the sources say

• Not checked yetcites Plovier et al., 2017 source

In the paper

“In vivo studies use widely varying methods of administration and concentrations of SCFAs, including oral uptake via enriched starch or drinking water, enema, and intraperitoneal injection.”

In the paper

“Concentrations of SCFAs provided with drinking water ranged from 36 mM to 300 mM in the studies cited above.”

In the paper

“A particularly striking example of the symbiotic effects of the microbiome is the immune system, whose cells depend critically on a diverse array of microbial metabolites for normal development and behavior.”

In the paper

“Disruptions to the microbiome have been shown to be associated with severe pathologies of the host including metabolic disease, cancer and inflammatory bowel disease.”

In the paper

“This is consistent with the notion that the intestinal microbiome is an important regulator of mucosal barrier function, which will be discussed in further detail in subsequent sections.”

In the paper

“Ffar2−/− mice had a similar defect, although no FFAR2 expression could be detected on microglia, leaving the connection between SCFAs and microglia unresolved (Erny et al., 2015).”

What the sources say

• Not checked yetcites Erny et al., 2015 source

In the paper

“Therefore, atherosclerosis is at least in part a disease of chronic inflammation, not unlike T2D.”

What the sources say

• Not checked yetcites Brophy et al., 2017 source
• Not checked yetcites Frostegård, 2013 source
• Not checked yetcites Moore et al., 2013 source

In the paper

“Second, microbiota-derived LPS has been suggested to traverse the mucosal barrier of the intestine on chylomicrons, lipoprotein complexes that transport long-chain fatty acids from the gut lumen to the lymph and blood (Ghoshal et al., 2009; Khan et al., 2014; Sonnenburg and Bäckhed, 2016).”

What the sources say

• Not checked yetcites Ghoshal et al., 2009 source
• Not checked yetcites Khan et al., 2014 source
• Not checked yetcites Sonnenburg and Bäckhed, 2016 source

In the paper

“Beyond these general mechanisms, the gut microbiome affects atherogenesis more specifically through its degradation of phosphatidylcholine, which is abundant in eggs, cheese, seafood and red meat (Jonsson and Bäckhed, 2017; Sharon et al., 2014; Sonnenburg and Bäckhed, 2016).”

What the sources say

• Not checked yetcites Jonsson and Bäckhed, 2017
• Not checked yetcites Sharon et al., 2014 source
• Not checked yetcites Sonnenburg and Bäckhed, 2016 source

In the paper

“The primary cause of cardiovascular disease is atherosclerosis, a process in which the microbiome has been implicated as well (Jonsson and Bäckhed, 2017; Sharon et al., 2014).”

What the sources say

• Not checked yetcites Jonsson and Bäckhed, 2017
• Not checked yetcites Sharon et al., 2014 source

In the paper

“Beyond intestinal macrophages, SCFAs have also been reported to be functionally important for microglia, a macrophage-like cell type of the central nervous system.”

What the sources say

• Not checked yetcites Erny et al., 2015 source

In the paper

“although no FFAR2 expression could be detected on microglia”

What the sources say

• Not checked yetcites Erny et al., 2015 source

In the paper

“Germ-free mice exhibited microglia dysfunction that could be rescued by treatment with SCFAs.”

What the sources say

• Not checked yetcites Erny et al., 2015 source

In the paper

“Several studies have demonstrated that butyrate and propionate inhibit the maturation of dendritic cells (DCs), which form a central bridge between the innate and adaptive immune systems (Lu Liu et al., 2012; Millard et al., 2002; Singh et al., 2010; B. Wang et al., 2008).”

What the sources say

• Not checked yetcites Lu Liu et al., 2012 source
• Not checked yetcites Millard et al., 2002 source
• Not checked yetcites Singh et al., 2010 source

In the paper

“It is hence not surprising that the same systemic, pro-inflammatory events that promote T2D also promote atherosclerosis (see above).”

In the paper

“In summary, microbiome-derived SCFAs are key regulators of virtually every aspect of the intestinal immune system.”

In the paper

“Nr1i2−/− mice exhibit impaired epithelial barrier function”

What the sources say

• Not checked yetcites Dou et al., 2013 source
• Not checked yetcites Garg et al., 2016 source
• Not checked yetcites Venkatesh et al., 2014 source

In the paper

“there is evidence that these differences affect experimental outcomes.”

In the paper

“Arpaia et al. detected no significant changes at a concentration of 36 mM”

What the sources say

• Not checked yetcites Arpaia et al., 2013 source

In the paper

“A role for SCFA in the regulation of B-cell function was reported nearly 20 years ago (Kudoh et al., 1998).”

What the sources say

• Not checked yetcites Kudoh et al., 1998 source

In the paper

“In Ido1−/− mice, which cannot produce the endogenous AhR ligand l-kynurenine, bacteria that are able to metabolize dietary tryptophan and produce indole derivatives gain a selective advantage due to the increased availability of tryptophan.”

What the sources say

• Not checked yetcites Zelante et al., 2013 source

In the paper

“Smith et al. reported an increase in cTregs after providing butyrate at a concentration of 150 mM with drinking water”

What the sources say

• Not checked yetcites Smith et al., 2013 source

In the paper

“Dietary tryptophan, for instance, is processed to several different indole derivatives, which can act as ligands for the aryl hydrocarbon receptor (AhR) in host cells (Wikoff et al., 2009).”

What the sources say

• Not checked yetcites Wikoff et al., 2009 source

In the paper

“whereas propionate and butyrate, but not acetate, increase the de novo differentiation of naive T cells into Tregs (Arpaia et al., 2013; Furusawa et al., 2013; Singh et al., 2014; Smith et al., 2013).”

What the sources say

• Not checked yetcites Arpaia et al., 2013 source
• Not checked yetcites Furusawa et al., 2013 source
• Not checked yetcites Singh et al., 2014 source

In the paper

“Direct application of 50 mM butyrate by enema, however, did elicit an increase in cTregs”

What the sources say

• Not checked yetcites Arpaia et al., 2013 source

In the paper

“Intriguingly, they further found that SCFAs in parallel modulate the energy metabolism of B cells to promote production of antibodies (M. Kim et al., 2016).”

What the sources say

• Not checked yetcites M. Kim et al., 2016 source

In the paper

“likely because this lower quantity of butyrate was largely absorbed by the upper gastrointestinal tract before reaching the colon (Arpaia et al., 2013; Smith et al., 2013).”

What the sources say

• Not checked yetcites Arpaia et al., 2013 source
• Not checked yetcites Smith et al., 2013 source

In the paper

“acetate and propionate, but not butyrate, stimulate the expansion of pre-existing colonic Tregs (cTregs)”

What the sources say

• Not checked yetcites Arpaia et al., 2013 source
• Not checked yetcites Furusawa et al., 2013 source
• Not checked yetcites Smith et al., 2013 source

In the paper

“The expansion of pre-existing cTregs is mediated by activation of FFAR2, which is not triggered effectively by butyrate (Smith et al., 2013).”

What the sources say

• Not checked yetcites Smith et al., 2013 source

In the paper

“the promiscuous nuclear receptor subfamily 1 group I member 2 (NR1I2, also known as pregnane X receptor, PXR) has been identified as a functional receptor for indole-3-propionic acid (IPA)”

What the sources say

• Not checked yetcites Venkatesh et al., 2014 source

In the paper

“Separately, butyrate has also been shown to enhance Treg generation by promoting an anti-inflammatory phenotype in macrophages and DCs through activation of HCAR2 (Singh et al., 2014).”

What the sources say

• Not checked yetcites Singh et al., 2014 source

In the paper

“However, SCFAs have also been shown to affect DC maturation and function through HCAR2 and FFAR3, depending on the context (Singh et al., 2014; Trompette et al., 2014).”

What the sources say

• Not checked yetcites Singh et al., 2014 source
• Not checked yetcites Trompette et al., 2014 source

In the paper

“Under homeostatic conditions, IL-22 is primarily produced by a specialized subset of intraepithelial lymphocytes, the type 3 innate lymphoid cells (ILC3s) (Melo-Gonzalez and Hepworth, 2017).”

What the sources say

• Not checked yetcites Melo-Gonzalez and Hepworth, 2017

In the paper

“Kim et al. shed further light on this observation and demonstrated that SCFAs support antibody responses by regulating gene expression through HDAC inhibition.”

What the sources say

• Not checked yetcites M. Kim et al., 2016 source

In the paper

“Conversely, the de novo differentiation of cTregs relies on HDAC inhibition in both DCs and T cells, which acetate does not promote (Arpaia et al., 2013; Furusawa et al., 2013).”

What the sources say

• Not checked yetcites Arpaia et al., 2013 source
• Not checked yetcites Furusawa et al., 2013 source

In the paper

“mice deficient for Card9, a gene that in humans is associated with IBD susceptibility, have an altered microbiota that produces lower amounts of indole derivatives, similar to the microbiota of IBD patients (Lamas et al., 2016).”

What the sources say

• Not checked yetcites Lamas et al., 2016 source

In the paper

“SCFAs have also been reported to promote generation of both effector and regulatory T cells, depending on the immunological context (Park et al., 2015).”

What the sources say

• Not checked yetcites Park et al., 2015 source

In the paper

“spermine administration exhibits protective anti-inflammatory effects in mouse models of both localized and systemic inflammation (Steege et al., 1999; M. Zhang et al., 1997; S. Zhu et al., 2009).”

What the sources say

• Not checked yetcites Steege et al., 1999 source
• Not checked yetcites M. Zhang et al., 1997 source
• Not checked yetcites S. Zhu et al., 2009 source

In the paper

“activation of GPBAR1 on macrophages and Kupffer cells by synthetic agonists inhibits the expression of LPS-induced pro-inflammatory cytokines by interfering with NF-κB-dependent transcription.”

What the sources say

• Not checked yetcites C. Guo et al., 2015 source
• Not checked yetcites Kawamata et al., 2003 source
• Not checked yetcites Keitel et al., 2008 source

In the paper

“Spermine and the monoamine histamine both inhibit activation of the NLRP6 inflammasome, a protein complex expressed by epithelial cells that regulates IL-18 secretion.”

What the sources say

• Not checked yetcites Levy et al., 2015 source

In the paper

“Consequently, the gut microbiota plays an important role in regulating the extent to which bile acids can be recycled by the host.”

In the paper

“blocking endogenous production of polyamines with a chemical inhibitor of ornithine decarboxylase negatively affects maintenance, repair and function of the intestinal epithelium”

What the sources say

• Not checked yetcites Chen et al., 2007 source
• Not checked yetcites X. Guo et al., 2005 source
• Not checked yetcites Lan Liu et al., 2009

In the paper

“the composition of bile acids varies dramatically between germ-free and control animals in feces, liver, heart, kidney and plasma (Duboc et al., 2013; Sayin et al., 2013; Swann et al., 2011).”

What the sources say

• Not checked yetcites Duboc et al., 2013 source
• Not checked yetcites Sayin et al., 2013 source
• Not checked yetcites Swann et al., 2011 source

In the paper

“Levy et al. recently reported that exogenous polyamines can reduce the release of IL-18, a cytokine that promotes epithelial repair and barrier function.”

What the sources say

• Not checked yetcites Levy et al., 2015 source

In the paper

“The highly reactive polyamines putrescine (a diamine, N2), spermidine (N3) and spermine (N4) all are arginine derivatives produced and secreted by intestinal bacteria (Michael, 2016).”

What the sources say

• Not checked yetcites Michael, 2016 source

In the paper

“the inflammatory effects of BAR deficiency on the liver may not only be mediated by Kupffer cells, but also by hepatocytes and NKT cells (Mencarelli et al., 2009; Y.-D. Wang et al., 2008).”

What the sources say

• Not checked yetcites Mencarelli et al., 2009 source
• Not checked yetcites Y.-D. Wang et al., 2008

In the paper

“These effects are primarily mediated by two different host receptors, the bile acid receptor (BAR; also known as nuclear receptor subfamily 1 group H member 4, NR1H4, or farnesoid X-activated receptor, FXR) and the G-protein-coupled bile acid receptor 1 (GPBAR1; also known as membrane-type receptor for bile acids, M-BAR, or TGR5).”

In the paper

“The cellular protein alpha-2-HS-glycoprotein (AHSG, also known as Fetuin-A) has been reported to be a required co-factor for the anti-inflammatory activity of spermine”

What the sources say

• Not checked yetcites H. Wang et al., 1997 source

In the paper

“Germ-free mice retain significantly higher amounts of arginine in their intestines than mice colonized by gut microbes.”

What the sources say

• Not checked yetcites Mardinoglu et al., 2015 source
• Not checked yetcites Matsumoto et al., 2012 source

In the paper

“bile acids reduce the expression of pro-inflammatory cytokines from monocytes, macrophages, DCs and the hepatic macrophages known as Kupffer cells (Brestoff and Artis, 2013; Martinot et al., 2017).”

What the sources say

• Not checked yetcites Brestoff and Artis, 2013 source
• Not checked yetcites Martinot et al., 2017 source

In the paper

“Both receptors can be activated by primary and secondary bile acids alike (Kawamata et al., 2003; Makishima et al., 1999; Maruyama et al., 2002; Parks et al., 1999; H. Wang et al., 1999).”

What the sources say

• Not checked yetcites Kawamata et al., 2003 source
• Not checked yetcites Makishima et al., 1999 source
• Not checked yetcites Maruyama et al., 2002 source

In the paper

“Oral administration of polyamines enhances the development and maintenance of the intestinal mucosa and resident immune cells (Buts et al., 1993; Dufour et al., 1988; Löser et al., 1999; Pérez-Cano et al., 2010).”

What the sources say

• Not checked yetcites Buts et al., 1993 source
• Not checked yetcites Dufour et al., 1988 source
• Not checked yetcites Löser et al., 1999 source

In the paper

“Specifically in the gut mucosa, P2X7 has been shown to be an important regulator of IgA secretion into the intestinal lumen.”

In the paper

“Binding of ATP to P2X7 results in the influx of Na+ and Ca2+ ions with simultaneous K+ efflux.”

In the paper

“However, no conclusive evidence for a causative role of bile-acid imbalances in the pathogenesis of IBD has been uncovered so far.”

In the paper

“presentation of SFB-derived antigens by intestinal APCs was shown to be sufficient for TH17 cell development (Goto et al., 2014; Panea et al., 2015).”

What the sources say

• Not checked yetcites Goto et al., 2014 source
• Not checked yetcites Panea et al., 2015 source

In the paper

“intraperitoneal injection of ATP exacerbated experimental colitis in mice (Atarashi et al., 2008).”

What the sources say

• Not checked yetcites Atarashi et al., 2008 source

In the paper

“Specifically, ATP elicits the production of cytokines that favor TH17 differentiation by CD70high CD11clow antigen-presenting cells (APCs) in the lamina propria (Atarashi et al., 2008).”

What the sources say

• Not checked yetcites Atarashi et al., 2008 source

In the paper

“Perruzza et al. recently demonstrated that microbially derived ATP can in fact modulate the host immune response through this pathway.”

What the sources say

• Not checked yetcites Perruzza et al., 2017 source

In the paper

“The subsequent reduction in B1-cell stimulation is believed to cause increased susceptibility of P2rx7−/− mice to polymicrobial sepsis (Proietti et al., 2014).”

What the sources say

• Not checked yetcites Proietti et al., 2014 source

In the paper

“A study evaluating genetic variations in NR1H4 found no association between single-nucleotide polymorphisms in this gene and IBD risk (Nijmeijer et al., 2011).”

What the sources say

• Not checked yetcites Nijmeijer et al., 2011 source

In the paper

“Monocolonization with a Shigella flexneri mutant unable to secrete ATP was associated with a significant increase in Tfh and germinal-center B cells, as well as elevated levels of bacteria-specific IgA in the intestine, compared to colonization with the ATP-secreting wild-type S. flexneri (Perruzza et al., 2017).”

What the sources say

• Not checked yetcites Perruzza et al., 2017 source

In the paper

“Gpbar1−/− mice, like their Nr1h4−/− counterparts, develop more severe disease than wildtype controls in several animal models of inflammatory disorder, including colitis, hepatitis and gastritis (Cipriani et al., 2011; C. Guo et al., 2015; Y.-D. Wang et al., 2011).”

What the sources say

• Not checked yetcites Cipriani et al., 2011 source
• Not checked yetcites C. Guo et al., 2015 source
• Not checked yetcites Y.-D. Wang et al., 2011

In the paper

“Another important microbial immune modulator is the zwitterionic PSA, produced by the common gut bacterium Bacteroides fragilis (Pantosti et al., 1991; Sharma et al., 2017) (Fig. 3).”

What the sources say

• Not checked yetcites Pantosti et al., 1991 source
• Not checked yetcites Sharma et al., 2017 source

In the paper

“Thus, microbially derived ATP appears to protect the intestinal microbiota from excessive antibody production under physiological conditions, which allows for mutually beneficial colonization of the host.”

In the paper

“Long-term activation of P2X7, however, results in formation of a large membrane pore and cell death (Nuttle and Dubyak, 1994; Smart et al., 2003).”

What the sources say

• Not checked yetcites Nuttle and Dubyak, 1994
• Not checked yetcites Smart et al., 2003 source

In the paper

“Entpd1−/− mice, which cannot remove extracellular ATP through this mechanism, where highly susceptible to experimental colitis (Friedman et al., 2009).”

What the sources say

• Not checked yetcites Friedman et al., 2009 source

In the paper

“They found that previous observations made in vivo could be robustly reproduced, while being able to extract compelling new insights due to the tightly controlled nature of their system (Yissachar et al., 2017).”

What the sources say

• Not checked yetcites Yissachar et al., 2017 source

In the paper

“The presence of PSA is a prerequisite for effective colonization of the colonic mucosa by its producer B. fragilis”

What the sources say

• Not checked yetcites Round et al., 2011 source

In the paper

“This process is supplemented by direct binding of PSA to TLR2 expressed on FoxP3+ Tregs, further enhancing IL-10 production (Round et al., 2011).”

What the sources say

• Not checked yetcites Round et al., 2011 source

In the paper

“the gut microbiota appears to influence nearly every aspect of host physiology, including energy balance, cardiovascular health, chronic inflammation, development of adaptive immune cells and many more systems that fall outside of the scope of this review (Rooks and Garrett, 2016; Sharon et al., 2014).”

What the sources say

• Not checked yetcites Rooks and Garrett, 2016
• Not checked yetcites Sharon et al., 2014 source

In the paper

“the up-regulation of ENTPD1 has been implicated in the protective effect of PSA in experimental autoimmune encephalomyelitis (EAE), a mouse model of multiple sclerosis (Ochoa-Reparaz et al., 2010; Y. Wang et al., 2014).”

What the sources say

• Not checked yetcites Ochoa-Reparaz et al., 2010 source
• Not checked yetcites Y. Wang et al., 2014

In the paper

“Yissachar et al. recently reported the development of a highly functional, microfluidics-based intestinal organ culture system.”

What the sources say

• Not checked yetcites Yissachar et al., 2017 source

In the paper

“an increase in ENTPD1 expression on peripheral-blood Tregs has been associated with remission of IBD (Gibson et al., 2015).”

What the sources say

• Not checked yetcites Gibson et al., 2015 source

In the paper

“This confirms that the immunomodulatory effects of PSA are not restricted to the intestinal compartment but have systemic consequences.”