S100A8 and S100A9 Are Important for Postnatal Development of Gut Microbiota and Immune System in Mice and Infants

Willers, Maike; Ulas, Thomas; Völlger, Lena; Vogl, Thomas; Heinemann, Anna S.; Pirr, Sabine; Pagel, Julia; Fehlhaber, Beate; Halle, Olga; Schöning, Jennifer; Schreek, Sabine; Löber, Ulrike; Essex, Morgan; Hombach, Peter; Graspeuntner, Simon; Basic, Marijana; Cloppenborg-Schmidt, Katja; Künzel, Sven; Jonigk, Danny; Rupp, Jan; Hansen, Gesine; Förster, Reinhold; Baines, John F.; Härtel, Christoph; Schultze, Joachim L.; Forslund, Kristoffer; Roth, Johannes; Viemann, Dorothee

doi:10.1053/j.gastro.2020.08.019

Cited by 92 publications

(84 citation statements)

References 72 publications

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“…4C): in the PMU, the PCo1 scores were signi cantly different among all time points except for P4. Altogether, these results align with previous ndings regarding taxonomic composition of the meconium and fecal samples [25,36], validating the microbial analysis methods used.…”

Section: Gut Microbiota Diversitysupporting

confidence: 89%

“…Moreover, they observed the increased abundance of the bacterial classes Actinobacteria, Bacteroidia [48][49][50] and Clostridia, along with the decreased abundance of Bacilli and Gammaproteobacteria over the same time period. Of note, Willers et al [25] demonstrated that during infancy, high abundance of Actinobacteria and low abundance of Gammaproteobacteria are linked to high fecal calprotectin levels; additionally, at the family level, fecal calprotectin promoted the higher abundance of Bi dobacteriaceae and the reduction of Enterobacteriaceae via the production of acetate [51]. Taxonomic composition observed by Willers et al [25] might be linked to the elevation in the synthesis and reduction in the degradation of short-chain fatty acids (SCFAs) and therefore leading to the overrepresentation of health-promoting gut microbiota metabolic functions.…”

Section: Discussionmentioning

confidence: 98%

“…[23,24] The sources of calprotectin in newborns are breast milk and resident and non-resident myeloid cells. [25] In fact, fecal calprotectin is used in older children and adults as a marker for in ammatory bowel diseases; there is a body of evidence correlating calprotectin with in ammatory bowel diseases, cow-milk allergy, atopic disease and other gastrointestinal disorders. [26] Of note, calprotectin has the potential to be used as an indirect marker of gut permeability.…”

Section: Introductionmentioning

confidence: 99%

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The Gut Microbiota is Associated with the Small Intestinal Paracellular Permeability and the Development of the Immune System in Healthy Children During the First Two Years of Life

Kaczmarczyk

Löber

Adamek

et al. 2021

Preprint

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BackgroundThe intestinal barrier plays an important role in the defense against infections, and nutritional, endocrine, and immune functions. The gut microbiota playing important role in development of the gastrointestinal tract can impact intestinal permeability and immunity during early life, but data concerning this problem are scare.MethodsWe analyzed the microbiota in fecal samples (101 samples in total) collected longitudinally over 24 months from 21 newborns to investigate whether the markers of small intestinal paracellular permeability (zonulin) and immune system development (calprotectin) are linked to the gut microbiota. The results were validated using data from an independent cohort that included the calprotectin and gut microbiota in children during the first year of life. ResultsZonulin levels tended to increase for up to 6 months after childbirth and stabilize thereafter remaining at a high level while calprotectin concentration was high after chilbirth and begun to decline from 6 months of life. The gut microbiota composition and the related metabolic potentials changed during the first two years of life and were correlated with zonulin and calprotectin levels. Feacal calprotectin correlated inversely with alpha diversity (Shannon index, r =-0.30, FDR P (Q)=0.039). It also correlated with seven taxa; i.a. negatively with Ruminococccaceae (r=-0.34, Q=0.046), and Clostridiales (r=-0.34, Q=0.048) and positively with Stapylococcus (r=0.38, Q=0.023) and Staphylococcaceae (r=0.35, Q=0.04), whereas zonulin correlated with 19 taxa; i.a. with Bacillales (r=-0.52, Q=0.0004), Clostridiales (r=0.48, Q=0.001) and the Ruminococcus (torques group) (r=0.40, Q=0.026). When time intevals were considered only changes in abundance of the Ruminococcus (torques group) were associcated with changes in calprotectin (β=2.94, SE=0.8, Q=0.015). The dynamics of stool calprotectin was negatively associated with changes in two MetaCyc pathways: pyruvate fermentation to butanoate (β=-4.54, SE=1.08, Q=0.028) and Clostridium acetobutylicum fermentation (β=-4.48, SE=1.16, Q=0.026). ConclusionsThe small intestinal paracellular permeability, immune system-related markers and gut microbiota change dynamically during the first two years of life. The Ruminococcus (torques group) seems to be especially involved in controlling paracellular permeability. Staphylococcus, Staphylococcaceae, Ruminococcaceae, and Clostridiales, may be potential biomarkers of the immune system. Despite observed correlations their clear causation and health consequences were not proven. Mechanistic studies are required.

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Section: Gut Microbiota Diversitysupporting

confidence: 89%

Section: Discussionmentioning

confidence: 98%

Section: Introductionmentioning

confidence: 99%

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The Gut Microbiota is Associated with the Small Intestinal Paracellular Permeability and the Development of the Immune System in Healthy Children During the First Two Years of Life

Kaczmarczyk

Löber

Adamek

et al. 2021

Preprint

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“…The consumption of specific food ingredients may modulate the gut microbiota composition and produce bacterial metabolites with effects on host health (6). After birth, the immune system matures via interactions with microbes in the gut and the interaction between the host and microbiota is considered to be fundamental for the development of the immune system (7,8). Observational findings during the past two decades suggest…”

Section: Introductionmentioning

confidence: 99%

Distinctive gut microbial dysbiosis between chronic alcoholic fatty liver disease and metabolic‑associated fatty liver disease in mice

et al. 2021

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The gut microbiota, which may affect normal physiological and biochemical functions, has an important role in the development of human liver diseases. The aim of the present study was to investigate differences in the gut microbiota between chronic alcoholic fatty liver disease (AFLD) and metabolic-associated fatty liver disease (MAFLD). AFLD was induced by chronic alcohol administration and MAFLD was induced by a Western-style diet in C57BL/6 mice. After 8 weeks, the levels of plasma alanine aminotransferase (ALT), aspartate aminotransferase (AST), triglyceride (TG), total cholesterol (TC), lipopolysaccharide (LPS), tumor necrosis factor (TNF)-α, interleukin (IL)-6, IL-1β and IL-10 were assessed and H&E staining of mouse liver tissue was performed. High-throughput sequencing of 16S ribosomal DNA from the intestinal contents was used to analyze the different effects of AFLD and MAFLD on the gut microbiota. Differences in the gut microbiota composition were assessed by the t-test. The results revealed increases in LPS, ALT, AST, TG, IL-1β and TNF-α in the AFLD group. Compared with those in the MAFLD control group, the MAFLD group exhibited increased plasma ALT, TG, TC, IL-6, IL-1β and TNF-α levels and decreased plasma IL-10 levels. In addition, the α-and β-diversities revealed that the AFLD and MAFLD groups exhibited obvious changes in the gut structure (with an increase in abundance in the AFLD group and a decrease in abundance in the MAFLD group). In comparison to the AFLD control group, Enterococcaceae were the most abundant bacteria at the family level and Enterococcus and Streptococcus were the most abundant bacteria at the genus level in the AFLD group. However, in the MAFLD group, Lachnospiraceae was the most abundant at the family level, with increases in Erysipelatoclostridium, Gordonibacter and Streptococcus at the genus level and a decrease in the genus Bifidobacterium. In conclusion, the present study confirmed that the AFLD and MAFLD groups harbored differences in the gut microbiota. The marked differences in the gut microbiota at the family and genus levels may contribute to the development process of FLD.

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“…One proposed mechanism is the stabilization of early immune-microbiome interaction by specific human milk abundant molecules such as alarmin S100 A8/A9. The latter has a pleiotropic effect on innate immunity including the prevention of gut dysbiosis and (sustained) inflammation [33][34][35]. A potential hallmark of children with hyperactivity/attention deficit problems is "mild inflammation", as characterized by increased interferon-gamma blood levels [36].…”

Section: Breastfeeding and Behavioral Outcome And Iq At School Agementioning

confidence: 99%

Breastfeeding for 3 Months or Longer but Not Probiotics Is Associated with Reduced Risk for Inattention/Hyperactivity and Conduct Problems in Very-Low-Birth-Weight Children at Early Primary School Age

et al. 2020

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(1) Background: We aimed to evaluate the effect of proposed “microbiome-stabilising interventions”, i.e., breastfeeding for ≥3 months and prophylactic use of Lactobacillus acidophilus/ Bifidobacterium infantis probiotics on neurocognitive and behavioral outcomes of very-low-birthweight (VLBW) children aged 5–6 years. (2) Methods: We performed a 5-year-follow-up assessment including a strength and difficulties questionnaire (SDQ) and an intelligence quotient (IQ) assessment using the Wechsler Preschool and Primary Scale of Intelligence (WPPSI)-III test in preterm children previously enrolled in the German Neonatal Network (GNN). The analysis was restricted to children exposed to antenatal corticosteroids and postnatal antibiotics. (3) Results: 2467 primary school-aged children fulfilled the inclusion criteria. In multivariable linear regression models breastfeeding ≥3 months was associated with lower conduct disorders (B (95% confidence intervals (CI)): −0.25 (−0.47 to −0.03)) and inattention/hyperactivity (−0.46 (−0.81 to −0.10)) as measured by SDQ. Probiotic treatment during the neonatal period had no effect on SDQ scores or intelligence. (4) Conclusions: Prolonged breastfeeding of highly vulnerable infants may promote their mental health later in childhood, particularly by reducing risk for inattention/hyperactivity and conduct disorders. Future studies need to disentangle the underlying mechanisms during a critical time frame of development.

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S100A8 and S100A9 Are Important for Postnatal Development of Gut Microbiota and Immune System in Mice and Infants

Cited by 92 publications

References 72 publications

The Gut Microbiota is Associated with the Small Intestinal Paracellular Permeability and the Development of the Immune System in Healthy Children During the First Two Years of Life

The Gut Microbiota is Associated with the Small Intestinal Paracellular Permeability and the Development of the Immune System in Healthy Children During the First Two Years of Life

Distinctive gut microbial dysbiosis between chronic alcoholic fatty liver disease and metabolic‑associated fatty liver disease in mice

Breastfeeding for 3 Months or Longer but Not Probiotics Is Associated with Reduced Risk for Inattention/Hyperactivity and Conduct Problems in Very-Low-Birth-Weight Children at Early Primary School Age

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