Microbes In Human Intestine Research Articles

Verification of utilization ability of Bifidobacterium and Lactobacillus to difructose anhydride III in vitro by its hydrolases and their application in Jerusalem artichoke tuber to improve nutrition

The functional Difructose anhydride III (DFA-III) lacks reported utilization by special probiotics of Bifidobacterium and Lactobacillus. DFA-III hydrolase (DFA-IIIase), converting DFA-III to inulobiose, is a critical enzyme for the metabolism of DFA-III, which stands for the utilization ability of DFA-III by microorganisms. Hence, the research identified six potential DFA-IIIases from Bifidobacterium and Lactobacillus species, suggesting that DFA-III has the potential to proliferate these bacteria. Notably, the DFA-IIIase from Bifidobacterium adolescentis belonging to the human intestinal microbe exhibits a hydrolysis rate of up to 67 % for DFA-III, which is the highest among the reported DFA-IIIases to date. When DFA-IIIases were applied to Jerusalem artichokes, DFA-III, inulobiose, and fructo-oligosaccharides were significantly produced. The in vitro work indicates that Bifidobacterium and Lactobacillus have the potential ability to utilize DFA-III by DFA-IIIases. Moreover, the first application of DFA-IIIase in Jerusalem artichokes provides valuable insights into comprehensive strategies for utilizing high-inulin agricultural products.

Limosilactobacillus reuteri promotes the expression and secretion of enteroendocrine- and enterocyte-derived hormones.

Observations that intestinal microbes can beneficially impact host physiology have prompted investigations into the therapeutic usage of such microbes in a range of diseases. For example, the human intestinal microbe Limosilactobacillus reuteri strains ATCC PTA 6475 and DSM 17938 are being considered for use for intestinal ailments including colic, infection, and inflammation as well as non-intestinal ailments including osteoporosis, wound healing, and autism spectrum disorder. While many of their beneficial properties are attributed to suppressing inflammatory responses in the gut, we postulated that L. reuteri may also regulate hormones of the gastrointestinal tract to affect physiology within and outside of the gut. To determine if L. reuteri secreted factors impact the secretion of enteric hormones, we treated an engineered jejunal organoid line, NGN3-HIO, which can be induced to be enriched in enteroendocrine cells, with L. reuteri 6475 or 17938 conditioned medium and performed transcriptomics. Our data suggest that these L. reuteri strains affect the transcription of many gut hormones, including vasopressin and luteinizing hormone subunit beta, which have not been previously recognized as being produced in the gut epithelium. Moreover, we find that these hormones appear to be produced in enterocytes, in contrast to canonical gut hormones which are produced in enteroendocrine cells. Finally, we show that L. reuteri conditioned media promotes the secretion of several enteric hormones including serotonin, GIP, PYY, vasopressin, and luteinizing hormone subunit beta. These results support L. reuteri affecting host physiology through intestinal hormone secretion, thereby expanding our understanding of the mechanistic actions of this microbe.

Effect of lactic acid bacteria by different concentrations of copper based on non-target metabolomic analysis.

Copper (Cu) is an essential element for mammals, but excess intake can have detrimental health consequences. However, Cu is no longer present in the "Limit of Contaminants in Foods" promulgated in 2022. The potential impact of different Cu (II) concentrations on human health remains unclear. In this study, a strain of lactic acid bacteria (LAB), namely, Lactiplantibacillus plantarum CICC 23121 (L23121), was selected as a prebiotic indicator strain to indirectly assess the effects of food-limited Cu (II) concentrations (issued by Tolerance limit of copper in foods in 1994) on the functions of intestinal microbes. We used non-target metabolomics, automatic growth curve detector, scanning electron microscopy (SEM), and Fourier transform infrared spectroscopy (FTIR) to investigate the effects of Cu (II) on L23121. The study revealed shows that the 50% minimum inhibitory concentration (MIC50) of Cu (II) for most lactic acid bacteria was 4 mg/L. At low Cu (II) concentrations (≤ 4 mg/L), the pentose phosphate pathway and pyrimidine metabolism of the lactic acid bacteria were affected, resulting in a decrease in the content of beneficial secondary metabolites and a significant decrease in the cell activity. As Cu (II) concentrations increase (≥ 6 mg/L), the key amino acid and lipid metabolisms were affected, leading to the inhibition of growth and primary metabolite production of the bacteria. Under high concentration of Cu (II) (6 mg/L), the surface adhesion of the bacteria was distorted and covered with significantly large particles, and the functional groups of the cells were significantly shifted. As a probiotic, the abundance of lactic acid bacteria in the intestine is significantly reduced, which will inevitably seriously damage intestinal homeostasis. Thus, to protect human intestinal microbes' health, it is recommended to limit the concentration of Cu in food to less than 4 mg/L.

Degradation profile of environmental pollutant 17β-estradiol by human intestinal fungus Aspergillus niger RG13B1 and characterization of genes involved in its degradation

Environmental hormones have attracted more attention because of their adverse impact on the health and ecological security of human. Biodegradation is still an efficient tactics to remove environmental hormones, but human intestinal microbes remain to be elucidated in the role of their degradation. In the present work, we intended to perform the in vitro experiment for investigating the degradation of 17β-estradiol, the main environmental estrogen, by human intestinal microflora Aspergillus niger RG13B1. Its degradation led to the production of eighteen metabolites characterized by 1H, 13C, and 2D NMR, and HRMS spectra, including nine new (1–9) and nine known metabolites (10–18). Based on their structures, the degradation pathway of 17β-estradiol mediated by A. niger RG13B1 involved hydroxylation, oxidation, methylation, acetylation, and dehydrogenation, especially infrequent lactylation, and the key degradation enzymes were found in the gene cluster of A. niger. In addition, we found that metabolite 12 interacted with amino acid residues Lys37, Gln39, Lys93, and Asn115 of NF-κB p65 to suppress expressions of inflammatory genes or proteins, exerting its anti-inflammatory effect. This study first illustrated the role of human gut microbe in 17β-estradiol degradation and provided new insights into its degradation mechanism by A. niger RG13B1.

Microbial stimulation of oxytocin release from the intestinal epithelium via secretin signaling

ABSTRACT Intestinal microbes impact the health of the intestine and organs distal to the gut. Limosilactobacillus reuteri is a human intestinal microbe that promotes normal gut transit, the anti-inflammatory immune system, wound healing, normal social behavior in mice, and prevents bone reabsorption. Oxytocin impacts these functions and oxytocin signaling is required for L. reuteri-mediated wound healing and social behavior; however, the events in the gut leading to oxytocin stimulation and beneficial effects are unknown. Here we report evolutionarily conserved oxytocin production in the intestinal epithelium through analysis of single-cell RNA-Seq datasets and imaging of human and mouse intestinal tissues. Moreover, human intestinal organoids produce oxytocin, demonstrating that the intestinal epithelium is sufficient to produce oxytocin. We find that L. reuteri facilitates oxytocin secretion from human intestinal tissue and human intestinal organoids. Finally, we demonstrate that stimulation of oxytocin secretion by L. reuteri is dependent on the gut hormone secretin, which is produced in enteroendocrine cells, while oxytocin itself is produced in enterocytes. Altogether, this work demonstrates that oxytocin is produced and secreted from enterocytes in the intestinal epithelium in response to secretin stimulated by L. reuteri. This work thereby identifies oxytocin as an intestinal hormone and provides mechanistic insight into avenues by which gut microbes promote host health.

Abstract A030: Gut microbiome as a promising biomarker for colorectal cancer diagnosis and immunotherapy response prediction

Abstract Background and objective: The association between human intestinal microbes and disease is an emerging topic in microbiome research, with potential implications in cancer diagnosis. Meanwhile, immune checkpoint inhibitor (ICI) therapy has been extensively applied to cancer patients but with relatively low overall response rate owing to pathological complexity. Thus, accurate prediction of cancer onset as well as patients’ response to ICI treatment through non-invasive methods, such as gut microbiome profiling, could greatly facilitate cancer diagnosis and treatment practice, which essentially improves patients’ quality of life. With the rapid accumulation of microbiome sequencing data and advanced machine learning algorithms, the use of gut microbiome as predictive biomarkers presents a feasible approach to address these problems. Methods and results: The first model we built is a predictive model for classifying healthy people from patients with colon cancer (CRC). The data (originated from Curated Metagenomics Data of Human Microbiome) consists of 166 fecal samples from healthy population and equal number of CRC patients from two studies (PRJEB24748, PRJEB6070). The data were divided into training and testing sets with a 3:1 ratio. Using the training dataset, we developed a Gradient Boosting Decision Tree model. To demonstrate the model's generalizability, we evaluated it using the testing dataset and the model achieved an AUC score of 0.93 (accuracy: 89%). Moreover, using an external independent cohort (which included 52 CRC patients from PRJEB12449 and 52 healthy individuals), we obtained an AUC score of 0.94 (accuracy: 88%). We also detected bacteria highly related to CRC pathology including Solobacterium_moorei, which could be potential biomarkers for CRC diagnosis. In addition, to predict CRC patients’ response to ICI, we built a random forest model based on patients’ fecal microbiome data before the ICI treatment. In total, stool metagenomics data from 63 CRC patients were used, including 30 patients responding to ICI treatment and 33 non-responders. With five-fold cross-validation, we achieved training and testing AUC score of 0.89 and 0.72, respectively. With an external data with 11 CRC patients’ samples, the classifier achieved an AUC of 0.78. Several microbial taxa were listed as important features contributing to the classification, e.g. Eubacterium hallii – a butyrate producer, which previously report to have a positive association with ICI clinical benefits. Conclusion: Using the non-invasive human gut microbiome data and advanced machine learning techniques, we present here two models with great performance to predict the occurrence of CRC and clinical response to ICI treatment in CRC patients. Similar strategy could be readily transferred to other cancer types to improve early diagnosis and patient stratification. Moreover, the microbial taxa identified to be essential features in the model could be developed as potential therapeutic targets. Citation Format: Die Dai, Xiaomin Xu, Wei Shen, Zhengnong Zhu, Fang Li, Xiaochen Yin, Yan Kou. Gut microbiome as a promising biomarker for colorectal cancer diagnosis and immunotherapy response prediction [abstract]. In: Proceedings of the AACR Special Conference on Colorectal Cancer; 2022 Oct 1-4; Portland, OR. Philadelphia (PA): AACR; Cancer Res 2022;82(23 Suppl_1):Abstract nr A030.

Response of human gut microbiota under simulated microgravity.

The present study was conducted to investigate the influence of microgravity on human gut microbiota using 16S rRNA gene sequencing in vitro. The diamagnetic material magnetic levitation method was used to simulate weightless environment. The human gut microbiota was cultured under two different conditions: normal gravity (1g), and simulated microgravity (0g), which showed that both the richness (P = 0.04) and diversity (P = 0.0002) of human gut microbiota were significantly altered. As compared to the normal gravity, the simulated microgravity significantly reduced abundance of bacteria related to anti-inflammatory effects, such as Subdoligranulum, Faecalibacterium, Fusicatenibacter, Butyricicoccus, and Lachnospiraceae-NK4A136-0 group (P < 0.05), while significantly increased that of Alistipes and Eubacterium-Ventriosum-group (P < 0.05). Moreover, the Spearman's correlation analysis showed that there were more significantly correlated species (|r|≥ 0.5, P < 0.05) in normal gravity than that in the simulated microgravity. KEGG pathway analysis revealed that the microgravity significantly (P < 0.05) affected the metabolism of gut microbiota, such as the metabolism of pyrimidine, fatty acids, glyoxylate and dicarboxylate, peptidoglycan biosynthesis, and carbon fixation in photosynthetic organisms. These results suggested that the exposure to a microgravity environment might induce disturbances in human gut microbiota. KEY POINTS: • Using 16sRNA gene sequencing technology, it was found that magnetic levitation-simulated microgravity had varying degrees of influence on the abundance, diversity, species correlation, and KEGG pathways of human intestinal microbes. • Digital PCR can improve the detection rate of microorganisms with low abundance.

Oxalobacter formigenes produces metabolites and lipids undetectable in oxalotrophic Bifidobacterium animalis

In the search for new potential therapies for pathologies of oxalate, such as kidney stone disease and primary hyperoxaluria, the intestinal microbiome has generated significant interest. Resident oxalate-degrading bacteria inhabit the gastrointestinal tract and reduce absorption of dietary oxalate, thereby potentially lowering the potency of oxalate as a risk factor for kidney stone formation. Although several species of bacteria have been shown to degrade oxalate, select strains of Oxalobacter formigenes (O. formigenes) have thus far demonstrated the unique ability among oxalotrophs to initiate a net intestinal oxalate secretion into the lumen from the bloodstream, allowing them to feed on both dietary and endogenous metabolic oxalate. There is significant interest in this function as a potential therapeutic application for circulating oxalate reduction, although its mechanism of action is still poorly understood. Since this species-exclusive, oxalate-regulating function is reported to be dependent on the use of a currently unidentified secreted bioactive compound, there is much interest in whether O. formigenes produces unique biochemicals that are not expressed by other oxalotrophs which lack the ability to transport oxalate. Hence, this study sought to analyze and compare the metabolomes of O. formigenes and another oxalate degrader, Bifidobacterium animalis subsp. lactis (B. animalis), to determine whether O. formigenes could produce features undetectable in another oxalotroph, thus supporting the theory of a species-exclusive secretagogue compound. A comparative metabolomic analysis of O. formigenes strain HC1 (a human isolate) versus B. animalis, another oxalate-degrading human intestinal microbe, was performed by ultra-high-performance liquid chromatography-high-resolution mass spectrometry (UHPLC-HRMS). Bacteria were cultured independently in anaerobic conditions, harvested, lysed, and extracted by protein precipitation. Metabolite extracts were chromatographically separated and analyzed by UHPLC-HRMS using reverse phase gradient elution (ACE Excel 2 C18-Pentafluorophenyl column) paired with a Q Exactive™ mass spectrometer. The purpose of this study was to assess whether O. formigenes potentially produces unique biochemicals from other oxalate degraders to better understand its metabolic profile and provide support for the theoretical production of a species-exclusive secretagogue compound responsible for enhancing intestinal oxalate secretion. We report a panel of metabolites and lipids detected in the O. formigenes metabolome which were undetectable in B. animalis, several of which were identified either by mass-to-charge ratio and retention time matching to our method-specific metabolite library or MS/MS fragmentation. Furthermore, re-examination of data from our previous work showed most of these features were also undetected in the metabolomes of Lactobacillus acidophilus and Lactobacillus gasseri, two other intestinal oxalate degraders. Our observation of O. formigenes metabolites and lipids which were undetectable in other oxalotrophs suggests that this bacterium likely holds the ability to produce biochemicals not expressed by at least a selection of other oxalate degraders. These findings provide support for the hypothesized biosynthesis of a species-exclusive secretagogue responsible for the stimulation of net intestinal oxalate secretion.

Phenolics and Carbohydrates in Buckwheat Honey Regulate the Human Intestinal Microbiota.

Intestinal microbiota plays an important role in human health. The aim of this paper is to determine the impact of the phenolics and carbohydrate in buckwheat honey on human intestinal microbiota. We investigated the phenolics and carbohydrate compositions of eight buckwheat honey samples using high-performance liquid chromatography and ion chromatography. The human intestinal microbes were cultured in a medium supplemented with eight buckwheat honey samples or the same concentration of fructooligosaccharides. The bacterial 16S rDNA V4 region sequence of DNA extraction was determined by the Illumina MiSeq platform. 12 phenolics and 4 oligosaccharides were identified in almost all buckwheat honey samples, namely, protocatechuic acid, 4-hydroxy benzoic acid, vanillin, gallic acid, p-coumaric acid, benzoic acid, isoferulic acid, methyl syringate, trans,trans-abscisic acid, cis,trans-abscisic acid, ferulic acid, 4-hydroxybenzaldehyde, kestose, isomaltose, isomaltotriose, and panose. Most notably, this is the first study to reveal the presence of 4-hydroxybenzaldehyde in buckwheat honey. 4-Hydroxybenzaldehyde seems to be a land marker of buckwheat honey. Our results indicate that buckwheat honey can provide health benefits to the human gut by selectively supporting the growth of indigenous Bifidobacteria and restraining the pathogenic bacterium in the gut tract. We infer that buckwheat honey may be a type of natural intestinal-health products.

Insight about Colonic Microbiota Imbalance and Obesity

Since the 1990s, nutritionists have concluded that poor food hygiene, as well as environmental and food pollution, are the cause of the major serious diseases affecting humanity: overweight and obesity, which induce persistent systemic pro-inflammatory status, and hence all complications metabolic disorders, cancers, joint diseases, skin disorders, psychological disorders. The human body hosts a large number of microbes, including bacterial, fungal and protozoal microorganisms, which together constitute our microbe. Dysbiosis, generated by a sedentary lifestyle, consuming highly industrialized food, and non-compliance with the mass program, can lead to obesity, with a decrease in quality of life and shortening it. Obesity and metabolic disorders related to obesity are characterized by specific changes in the composition and function of the human intestinal microbe. Among the possible strategies for preventing and/or treating obesity, the microbiota is intended to restore or modulate its composition by consuming probiotics, prebiotics or both (synbiotics).

Detection and characterization of bacterial nucleic acids in culture-negative synovial tissue and fluid samples from rheumatoid arthritis or osteoarthritis patients

Human intestinal microbes can mediate development of arthritis – Studies indicate that certain bacterial nucleic acids may exist in synovial fluid (SF) and could be involved in arthritis, although the underlying mechanism remains unclear. To characterize potential SF bacterial nucleic acids, we used 16S rRNA gene amplicon sequencing to assess bacterial nucleic acid communities in 15 synovial tissue (ST) and 110 SF samples from 125 patients with rheumatoid arthritis (RA) and 16 ST and 42 SF samples from 58 patients with osteoarthritis (OA). Our results showed an abundant diversity of bacterial nucleic acids in these clinical samples, including presence of Porphyromonas and Bacteroides in all 183 samples. Agrobacterium, Comamonas, Kocuria, Meiothermus, and Rhodoplanes were more abundant in synovial tissues of rheumatoid arthritis (STRA). Atopobium, Phascolarctobacterium, Rhodotorula mucilaginosa, Bacteroides uniformis, Rothia, Megasphaera, Turicibacter, Leptotrichia, Haemophilus parainfluenzae, Bacteroides fragilis, Porphyromonas, and Streptococcus were more abundant in synovial tissues of osteoarthritis (STOA). Veillonella dispar, Haemophilus parainfluenzae, Prevotella copri and Treponema amylovorum were more abundant in synovial fluid of rheumatoid arthritis (SFRA), while Bacteroides caccae was more abundant in the synovial fluid of osteoarthritis (SFOA). Overall, this study confirms existence of bacterial nucleic acids in SF and ST samples of RA and OA lesions and reveals potential correlations with degree of disease.

Identification of naringin metabolites mediated by human intestinal microbes with stable isotope-labeling method and UFLC-Q-TOF-MS/MS

Widely presented in medicinal plants, naringin is one of the major flavanones with various pharmaceutical bioactivities. After oral administration, naringin predominantly undergoes metabolisms mediated by liver cytochrome P450 and gut microbes, while its human microbes-mediated metabolic profiling is still largely obscure due to the endogenous interferences, which makes it extremely difficult to analyze metabolites precisely. In this study, we aim of systematically investigating the biotransformation of naringin mediated by human intestinal microbes through applying stable isotope-labeling method. [2′,3′,5′,6′-D4]naringin was synthesized and incubated anaerobically with human gut microbes. A total of 13 microbial metabolites were detected and identified by UFLC-Q-TOF-MS/MS, among which 5 were reported for the first time. Furthermore, the proposed metabolic pathway revealed that naringin went through extensive phase I metabolism in human intestinal microbes. Of note, diverse metabolic profiles of naringin among human participants were obtained, which could be attributed to the distinct gut microbiota compositions of individuals.

Effects of a homogeneous polysaccharide from Sijunzi decoction on human intestinal microbes and short chain fatty acids in vitro

Ethnopharmacological relevanceSijunzi decoction (SJZD) is a classic recipe in traditional Chinese medicine (TCM) to strengthen the spleen and replenish Qi. It is well known for treating disorders of gastrointestinal function manifested in poor appetite, reduced food intake and loose stools. Polysaccharide is the most abundant constituent and the major effective component in SJZD. Aim of the studyThe present study aimed to understand the immunomodulatory mechanism of S-3–1, a homogeneous polysaccharide purified from SJZD with immune-enhancement activity, by investigating its effects on human intestinal microbes and short chain fatty acids. Materials and methodsS-3–1 was incubated with simulated gastric juice, intestinal juice, and human fecal microflora independently and sequentially. The concentrations of total polysaccharide and reducing sugar were measured to identify the stability of independently and sequentially incubated S-3–1 in three in vitro fermentation models. Gas chromatograph (GC) analysis was used to measure the short chain fatty acid (SCFA) contents in human fecal samples. The human gut microbiota composition was measured by 16S rRNA gene Illumina MiSeq sequencing (V3-V4 region). ResultsS-3–1 was degraded in three in vitro fermentation models separately and sequentially. Both S-3–1 and incubated S-3–1 could regulate the abundances of Lactobacillus, Pediococcus, Streptococcus, Bacteroides, Enterococcus, Clostridium and Dorea in human intestinal microflora samples. Specifically, S-3–1 could only regulate the abundances of Paraprevotella and Oscillospira, while the influenced flora changed to Butyricimonas, Coprococcus, Dialister, Sutterella, Ruminococcus and Parabacteroides after sequential incubation of S-3–1. In contrast to S-3–1 showing no influence on the content of SCFA, incubated S-3–1 showed increased contents of acetic acid and total acid that were associated with its effects on the abundances of Enterococcus, Sutterella, Butyricimonas and Streptococcus. ConclusionS-3–1 plays an immunomodulatory role by regulating the abundances of 9 intestinal bacteria genera. Incubated S-3–1 can regulate more bacteria genera, a total of 13 kinds, and can adjust the SCFA content to affect immunomodulation. Incubation with gastric and intestinal juices enhanced S-3–1′s capability of modulating the intestinal flora composition and decreased the bacteria’s need for a carbon source. This study could provide new insights for studies on the pharmacological mechanisms of polysaccharides in vitro.

Microbial Metabolism in the Mammalian Gut: Molecular Mechanisms and Clinical Implications.

Human intestinal microbes participate actively at the interface of diet, nutrition, and overall health status. These biodiverse communities of microorganisms have a broader metabolic repertoire compared with their host, and they are able to synthesize and degrade substrates that would be otherwise unavailable. In recent years, we have recognized that healthy microbial communities are important for energy harvest and the regulation of body systems outside the digestive tract. Microbial dysbiosis, however, has been implicated in a number of human disorders, including obesity and inflammation. This dichotomy highlights the need to understand the factors that determine the composition and metabolic output of our resident and transient microbes. Throughout the human lifespan, we know that diet plays a major role in shaping gut microbial communities, as well as directing the types and amounts of metabolites produced. Understanding the factors that affect microbial metabolic output within the host may help identify the roles of microbes in health, as well as new targets for treatment in disease. In this article, we review facets of the assembly and activities of the healthy human intestinal microbiome, as well as ways that the microbiota has been shown to influence the host via metabolism of two dietary macronutrients: carbohydrates and amino acids.

Enteric coating of granules containing the probiotic Lactobacillus acidophilus.

In the present study, a capsule formulation composed of enteric coated granules of Lactobacillus acidophilus ATCC 4962 was developed using Eudragit L30D-55 as enteric polymer. Optimization of the capsule formulation was achieved with a maximum viable cell count after 2 h of incubation in acid medium and disintegration time of 1 h in buffer pH 6.8. The amount of Eudragit L30D-55 in the capsules correlated with gastric juice resistance. The best protective qualities against artificial gastric juice were observed when capsules were prepared from granules composed of L. acidophilus, corn starch, lactose monohydrate, polyvinylpyrrolidone and coated with 12.5 % (m/V) of Eudragit L30D-55. Capsule formulation of L. acidophilus in edible broth medium suspension serves as a cheap alternative to the expensive freeze-drying procedure for preparing L. acidophilus. In addition, the enteric coating using Eudragit L30D-55 could protect probiotics from the acidic gastric environment and enhance the bioactivity of probiotics along with replacement of pathogenic microbes in human intestine.

Principal human milk oligosaccharides utilized by human gut microbiota

Human milk oligosaccharides are poorly digested and absorbed in the small intestine, allowing their passage into the colon, where they influence colonization by the microbiota. The ability of individual major fucosylated and sialylated human milk oligosaccharides to promote growth and physiologic activity of 25 human intestinal microbes was investigated. 2′‐Fucosyllactose, 3‐ Fucosyllactose, and Lactodifucotetraose stimulated most Bifidobacteria spp. and Bacteroides spp. to grow and produce abundant lactate or short chain fatty acids. 3′‐sialyllactose and 6′‐ sialyllactose promoted moderate growth of B. longum JCM7007, 7009, 7010, 7011, 1272, 11347, ATCC15708, B. thetaiotaomicron ATCC29148, and C. leptum ATCC29065; these bacteria produced lactate or short chain fatty acids or both. In contrast, L. rhamnosus ATCC53103, E. facalis ATCC29200, S. epidermidis ATCC12228 and E. coli K12 did not consume the milk oligosaccharides. In summary, specific Bifidobacteria and Bacteroides differentially digest specific individual human milk oligosaccharides, especially the major fucosylated milk oligosaccharides, and these may prove useful for treating dysbiosis of the microbiota and associated inflammatory disorders.Grant Funding Source: HD013021, AI075563, and Abbott Nutrition

Toward defining the autoimmune microbiome for type 1 diabetes

Several studies have shown that gut bacteria have a role in diabetes in murine models. Specific bacteria have been correlated with the onset of diabetes in a rat model. However, it is unknown whether human intestinal microbes have a role in the development of autoimmunity that often leads to type 1 diabetes (T1D), an autoimmune disorder in which insulin-secreting pancreatic islet cells are destroyed. High-throughput, culture-independent approaches identified bacteria that correlate with the development of T1D-associated autoimmunity in young children who are at high genetic risk for this disorder. The level of bacterial diversity diminishes overtime in these autoimmune subjects relative to that of age-matched, genotype-matched, nonautoimmune individuals. A single species, Bacteroides ovatus, comprised nearly 24% of the total increase in the phylum Bacteroidetes in cases compared with controls. Conversely, another species in controls, represented by the human firmicute strain CO19, represented nearly 20% of the increase in Firmicutes compared with cases overtime. Three lines of evidence are presented that support the notion that, as healthy infants approach the toddler stage, their microbiomes become healthier and more stable, whereas, children who are destined for autoimmunity develop a microbiome that is less diverse and stable. Hence, the autoimmune microbiome for T1D may be distinctly different from that found in healthy children. These data also suggest bacterial markers for the early diagnosis of T1D. In addition, bacteria that negatively correlated with the autoimmune state may prove to be useful in the prevention of autoimmunity development in high-risk children.