children, crohns, and gut health

[cheka]

researchers in this study think they are onto it. call for more research into microbiome therapies

https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7304104/
Intestinal dysbiosis in pediatric Crohn's disease patients with IL10RA mutations


Core tip: Understanding the role of microbes in sub-populations of inflammatory bowel disease patients is important. The focus on this relatively unique and uniform interleukin (IL)10RA group provides an excellent opportunity. In this study, clinical variables of IL10RA-deficient patients (such as disease course) were linked with changes in the stool microbiome, which implies potential clinical relevance of the changes in microbial populations.

Gevers et al[24] reported the microbial dysbiosis in new-onset pediatric CD: Increased abundance of Enterobacteriaceae, Pasteurellacaea, Veillonellaceae, and Fusobacteriaceae and decreased abundance of Erysipelotrichales, Bacteroidales, and Clostridiales. A systematic review showed that patients with active CD have lower abundance of Clostridium leptum, Faecalibacterium prausnitzii, and Bifidobacterium[26]. Consistent with previous studies, we observed increased Veillonellaceae in the CD group; Clostridiales and Bifidobacterium were decreased in the IL10RA group regardless of the antibiotic exposure.

In summary, the advent of new methodologies can facilitate a better understanding of the interactions between genetic factors and the gut microbiome. To the best of our knowledge, this is the first report of microbial dysbiosis in this sub-population of IBD patients with IL10RA mutations; our findings may facilitate further attempts to develop microbial therapeutics. Gut dysbiosis in patients with IL10RA mutations showed a moderate association with disease severity in this study. Further studies should focus on the precise role of the microbiota in the etiology of IBD in terms of host genetic susceptibility; this constitutes an attractive target for a given host genome.

 

[cheka]

here we go again -- low butyrate caused by low butyrate producers, namely the bifid family of bugs

bifid infantis gets a couple of mentions as a therapy -- this is part of mother's milk. shortages of this bifid bug havee been linked to other diseases too

https://www.nature.com/articles/s41598-019-55290-9
Differences in the intestinal microbiome of healthy children and patients with newly diagnosed Crohn’s disease

The aetiology of inflammatory bowel diseases (IBD) seems to be strongly connected to changes in the enteral microbiome. The dysbiosis pattern seen in Crohn’s disease (CD) differs among published studies depending on patients’ age, disease phenotype and microbiome research methods. The aims was to investigate microbiome in treatment-naive paediatric patients to get an insight into its structure at the early stage of the disease in comparison to healthy.

Statistically significant dissimilarities between samples were present for all used metrics. We also found a significant increase in the abundance of OTUs of the Enterococcus genus and reduction in, among others, Bifidobacterium (B. adolescentis), Roseburia (R.faecis), Faecalibacterium (F. prausnitzii), Gemmiger (G. formicilis), Ruminococcus (R. bromii) and Veillonellaceae (Dialister).

Moreover, differences in alpha and beta diversities in respect to calprotectin and PCDAI were observed: patients with calprotectin <100 µg/g and with PCDAI below 10 points vs those with calprotectin >100 µg/g and mild (10–27.7 points), moderate (27.5–40 points) or severe (>40 points) CD disease activity had higher richness and diversity of gut microbiota. The results of our study highlight reduced diversity and dysbiosis at the earliest stage of the disease. Microbial imbalance and low abundance of butyrate-producing bacteria, including Bifidobacterium adolescentis, may suggest benefits of microbial modification therapy.

The most frequently observed changes are decrease in Bacteroides and Firmicutes and increase in Actinobacteria and Gammaproteobacteria10. CD patients’ intestinal microbiome was shown to be poor in Faecalibacterium prausnitzii, commensal bacteria with anti-inflammatory properties11, Roseburia intestinalis and other butyrate-producing bacteria

In our cohort of treatment-naïve CD patients, a reduction in microbiota diversity and richness compared to healthy controls was shown. We found that 11 genera and 17 species differed significantly between CD patients and HC. The respective alteration was observed in OTUs belonging to Actinobacteria and Firmicutes.

In general, however, we support the authors’ opinion that IBD microbiome is characterized more by diminishing abundance of certain bacterial species than by an increase in pathogens. In the study conducted by Kugathasan et al., 14 genera associated with CD were identified with the largest increase in Aggregatibacter and the greatest decrease in Roseburia and SCFA-producing bacteria

Our results support the theory that lack of F. prausnitzii and B. adolescentis in the stool can serve, although not always with statistical significance, as a biomarker signal of dysbiosis typical for CD13,33. Pascal et al. have attempted to establish microbial biomarkers of CD and the results obtained by them give hope for the creation of a promising non-invasive diagnostic method in CD suspected patients with nonspecific signs of disease39. We have also observed a decrease in the abundance of Roseburia in newly diagnosed children, which may contribute to the suggestion of Imhann et al. that these changes can precede the onset of IBD

Environment, diet and genetic background seem to be key players in the creation of gut microbiota. Ashton et al. observed compositional changes in microbiota between individual patients as well as differences between patients and healthy controls45. Interestingly, the microbiome in untreated patients and their healthy siblings showed some similarity which may confirm the role of environment and dietary habits in microbiome composition. On the other hand, Ijaz et al. showed that the microbiome in healthy adult relatives of paediatric CD patients is more similar to the microbiome in healthy adult controls46. Joossens et al. did not reveal the same type of dysbiosis as in CD patients either in unaffected relatives or healthy controls35. Those two studies may confirm that alteration in microbiome composition is related more strongly to the illness itself than to genetic background and nutritional habits or is related to some other environmental factors.

The study investigating microbiome in treatment-naïve new-onset paediatric CD patients confirmed that alteration in abundance of several taxa and diminished richness of taxa was related to the intensity of inflammation12. We have also observed a decrease in alpha and beta diversities with an increased level of faecal calprotectin and higher disease activity index (PCDAI). This indicates a link between dysbiosis and inflammation of the gastrointestinal tract.

If the change in intestinal microflora is one of the risk factors for the development and / or persistence of inflammation in IBD, then the microbiome-oriented treatment should be a component of the therapeutic goals. Such treatment methods as antibiotics, pro- and prebiotics as well as faecal microbiota transplant can be taken into account. Furthermore, considering the relationship between microbiota and genetic predisposition, the usefulness of a microbiome-based preventive treatment in high-risk groups may be considered.

Consistent data confirming low abundance and diversity of Bifidobacterium in CD patients suggest that further studies are needed to answer the question whether it is possible to use Bifidobacterium adolescentis as a probiotic.

 

[cheka]

https://www.frontiersin.org/articles/10.3389/fped.2021.626232/full
Gut Microbiota Profile in Pediatric Patients With Inflammatory Bowel Disease: A Systematic Review

Accumulating evidence have implicated gut microbiota alterations in pediatric and adult patients with inflammatory bowel disease (IBD); however, the results of different studies are often inconsistent and even contradictory. It is believed that early changes in new-onset and treatment-naïve pediatric patients are more informative. We performed a systematic review to investigate the gut microbiota profiles in pediatric IBD and identify specific microbiota biomarkers associated with this disorder.

A total of 41 original studies investigating gut microbiota profiles in pediatric patients with IBD were included in this review. Several studies have reported a decrease in α-diversity and an overall difference in β-diversity. Although no specific gut microbiota alterations were consistently reported, a gain in Enterococcus and a significant decrease in Anaerostipes, Blautia, Coprococcus, Faecalibacterium, Roseburia, Ruminococcus, and Lachnospira were found in the majority of the included articles.

This systematic review identified evidence for differences in the abundance of some bacteria in pediatric patients with IBD when compared to patients without IBD

In addition, children with IBD exhibit a more severe course, especially those with a very early onset. Although the detailed pathogenesis of IBD remains unexplained, genetic predisposition, dietary patterns, inappropriate immune responses, and environmental factors have been reported to be closely associated with IBD (7–10). Though genetic factors seem to play a great role in patients with pediatric-onset IBD, environmental and microbial factors show a more prominent role in the occurrence and development of this disease in pediatric patients (11–13).

At the phylum level, a decreased abundance of Actinobacteria and Bacteroidetes, and an increased abundance of Proteobacteria were reported in pediatric patients with CD, which is similar to the results of studies that assessed adult patients.

Additionally, several studies have demonstrated a significant decrease in the orders Bacteroidales, Clostridiales, Bifidobacteriales, and Erysipelotrichales as well as an increase in Enterobacteriales and Fusobacteriales. In terms of lower taxonomic levels, previous studies have demonstrated inconclusive results of gut microbiota alterations in pediatric patients with CD. Even so, a decreased relative abundance of several genera belonging to the families Lachnospiraceae (Anaerostipes, Blautia, Coprococcus, Lachnospira, and Roseburia), Ruminococcaceae (Anaerotruncus, Faecalibacterium, and Ruminococcus), Clostridium, Holdemania, Odoribacter, Parabacteroides, and Turicibacter were reported in most included studies. In addition, the abundance of the genera Actinomyces, Corynebacterium, Enterococcus, Escherichia, Fusobacterium, Granulicatella, Sutterella, and Veillonella were assessed in several studies.

Although the gut microbiome changes throughout a patient's life, no systematic changes were found in patients with CD with different ages of diagnosis, suggesting that CD-associated dysbiosis is already established in younger CD patients.

Although no conclusive determinations can be made, a diminished richness of the taxa and alterations of several specific bacteria have been reported to be associated with disease activity. Kaakoush et al. reported that the detection frequencies of Bacteroidetes and Firmicutes correlated (positively and negatively, respectively) with the calculated pediatric CD activity index (PCDAI) scores of patients. However, findings from Haberman et al. demonstrated that PCDAI scores were positively associated with Gammaproteobacteria and Enterobacteriaceae and negatively associated with Clostridiales and Bacteroides.

Furthermore, Mottawea et al. found that major short-chain fatty acids (SCFA) producers such as Lachnospiraceae, Blautia, Roseburia, Ruminococcus, Clostridium, and Faecalibacterium were negatively correlated with disease severity, while some H2S producers such as Atopobium, Fusobacterium, Veillonella, Prevotella, Streptoccocus, and Leptotrichia were positively correlated with disease severity. Additionally, Gevers et al. assessed that the microbial dysbiosis index showed a strong positive correlation with PCDAI, and the levels of Fusobacterium and Haemophilus were positively correlated with PCDAI, which was further confirmed in a study by Shaw et al. Maukonen et al. found that Bacteroides was the only bacterial group in which lower disease activity was associated with higher bacterial numbers in both UC and CD. In addition, Xue et al. found a significant correlation between PCDAI and Simplified Endoscopic Score for Crohn's Disease (SES-CD) scores and the dysbiosis indices (Lactobacillales, Micrococcales, Veillonellaceae, Clostridiales, and Selenomonadales).

Several studies have reported that the microbiota composition changes gradually with time, and that even though the gut microbiota begins to resemble the adult flora by 3 years of age, it is crucial to study the gut microbiota of pediatric patients with IBD

In the majority of the studies included in this review, a decreased microbial biodiversity with alterations in the composition of the gut microbiota community was observed in fecal and mucosal samples from pediatric patients with IBD

These findings suggest that the previously reported dysbiosis in patients with adult-onset IBD may be established during the pediatric period. In recent years, there is accumulating evidence suggesting that alterations in the metabolites of the gut microbiota and specific bacterial metabolic pathways may help elucidate the precise cause-effect mechanistic relationships between gut microbiota and IBD, which may result in new discoveries regarding the pathogenesis and therapeutic methods for this disease