Could Artificial Intelligence/Machine Learning and Inclusion of Diet-Gut Microbiome Interactions Improve Disease Risk Prediction? Case Study : Coronary Artery Disease

Funding Information: This research was funded by the Latvian Council of Science within the project Gut microbiome composition and diversity among health and lifestyle induced dietary regimen, project No. lzp-2018/2-0266. Publisher Copyright: Copyright © 2022 Vilne, Ķibilds, Siksna, Lazda, Valciņa and Krūmiņa.Coronary artery disease (CAD) is the most common cardiovascular disease (CVD) and the main leading cause of morbidity and mortality worldwide, posing a huge socio-economic burden to the society and health systems. Therefore, timely and precise identification of people at high risk of CAD is urgently required. Most current CAD risk prediction approaches are based on a small number of traditional risk factors (age, sex, diabetes, LDL and HDL cholesterol, smoking, systolic blood pressure) and are incompletely predictive across all patient groups, as CAD is a multi-factorial disease with complex etiology, considered to be driven by both genetic, as well as numerous environmental/lifestyle factors. Diet is one of the modifiable factors for improving lifestyle and disease prevention. However, the current rise in obesity, type 2 diabetes (T2D) and CVD/CAD indicates that the “one-size-fits-all” approach may not be efficient, due to significant variation in inter-individual responses. Recently, the gut microbiome has emerged as a potential and previously under-explored contributor to these variations. Hence, efficient integration of dietary and gut microbiome information alongside with genetic variations and clinical data holds a great promise to improve CAD risk prediction. Nevertheless, the highly complex nature of meals combined with the huge inter-individual variability of the gut microbiome poses several Big Data analytics challenges in modeling diet-gut microbiota interactions and integrating these within CAD risk prediction approaches for the development of personalized decision support systems (DSS). In this regard, the recent re-emergence of Artificial Intelligence (AI) / Machine Learning (ML) is opening intriguing perspectives, as these approaches are able to capture large and complex matrices of data, incorporating their interactions and identifying both linear and non-linear relationships. In this Mini-Review, we consider (1) the most used AI/ML approaches and their different use cases for CAD risk prediction (2) modeling of the content, choice and impact of dietary factors on CAD risk; (3) classification of individuals by their gut microbiome composition into CAD cases vs. controls and (4) modeling of the diet-gut microbiome interactions and their impact on CAD risk. Finally, we provide an outlook for putting it all together for improved CAD risk predictions.publishersversionPeer reviewe

Retrospective study of genetic diversity of Acinetobacter baumannii -resistant strains isolated from patients in Riga East University Hospital in Latvia

Affiliations are different in Web of Science database and original journal publication. Here are given affiliations from original publication in Proceedings of the Latvian Academy of Sciences, Section B: Natural Exact and Applied Sciences.publishersversionPeer reviewe

Microbial Community of Kefir and its Impact on the Gastrointestinal Microbiome in Health and Disease

Kefir is a fermented dairy product, created by fermentation of milk by bacteria and yeasts. Kefir is the most common traditional non-sweetened fermented dairy beverage in the Baltic countries. Whole kefir and specific fractions and individual organisms isolated from kefir provide a multitude of health benefits, including regulation of composition of the gut microbiome. This review aims to summarise the available data about influence of kefir consumption on the gut microbiome in healthy individuals and to highlight the effects that kefir consumption as well as separated fractions of kefir can have in disease states via modulation of the host microbiome.publishersversionPeer reviewe

The Gut Microbiome among Postmenopausal Latvian Women in Relation to Dietary Habits

Funding Information: This research was funded by the Project “Scientifically substantiated fermented milk products development and their clinical studies”, grant number 19-00-A01612-000009, financed by European agricultural fund for rural development. Publisher Copyright: © 2022 by the authors.In recent years, many studies have been initiated to characterise the human gut microbiome in relation to different factors like age, lifestyle, and dietary habits. This study aimed to evaluate the impact of yoghurt intake on the gut microbiome among postmenopausal women and how overall dietary habits modulate the gut microbiome. In total, 52 participants were included in the study and two groups—a control (n = 26) and experimental group (n = 26)—were established. The study was eight weeks long. Both study groups were allowed to consume a self-selected diet, but the experimental group had to additionally consume 175 g of plain organic milk yoghurt on a daily basis for eight weeks. In addition, a series of questionnaires were completed, including a questionnaire on the subject’s sociodemographic background, health status, and lifestyle factors, as well as a food frequency questionnaire. Stool samples were collected for the analysis of the gut microbiome (both prior to and after the eight weeks of the study). Sequencing of V4-V5 regions of the 16S rRNA gene was used to determine the bacterial composition of stool samples. The dominant phylum from the gut microbiome was Firmicutes (~70% to 73%), followed by Bacteroidota (~20% to 23%). Although no significant changes in the gut microbiome were related to daily consumption of yoghurt, we report that consumption of food products like grains, grain-based products, milk and milk products, and beverages (tea, coffee) is associated with differences in the composition of the gut microbiome. Establishing nutritional strategies to shape the gut microbiome could contribute to improved health status in postmenopausal women, but further research is needed.publishersversionPeer reviewe

Effects of adenine limitation on morphology and physiology of yeast Saccharomyces cerevisiae cells

Audzējot barotnē ar ierobežotu adenīna daudzumu adenīna auksotrofu un prototrofu maizes rauga celmu, tika izpētīta adenīna limitācijas ietekme uz rauga šūnu morfoloģiskajiem parametriem. Tika novērots, ka pēc adenīna izsīkšanas barotnē auksotrofās šūnas pārstāj augt, taču turpinās kultūras optiskā blīvuma un sausā svara pieaugums. Reizē ar adenīna limitācijas iestāšanos šūnas sāk pastiprināti uzkrāt trehalozi, kā arī pieaug to izmēri. Salīdzinot šūnu izdzīvotību adenīna, leicīna un slāpekļa iztrūkuma apstākļos, atklājās, ka adenīna badinātas šūnas spēj efektīvāk arestēt šūnas ciklu G1/G0 fāzē un saglabāt ievērojami augstāku dzīvotspēju nekā leicīna badinātas šūnas. Adenīna limitācijā tika novērota arī glikozes izšķiešana. Iegūtie dati liecina, ka adenīna limitācijas fizioloģiskie procesi ir atšķirīgi no citām auksotrofajām limitācijām.Adenine auxotroph and prototroph strains of Saccharomyces cerevisiae were cultivated in a medium of limited adenine content in order to assay the effects of adenine limitation on morphological parameters of yeast cells. It was observed that cellular growth ceased in response to adenine depletion. However, increase in optical density of the adenine-limited culture persisted along with increase in mean cell size and dry weight. A substantial rise in levels of accumulated trehalose was coincident with adenine depletion. An assay of survival and cell cycle arrest was carried out among yeast cells starved for adenine, leucine and nitrogen. It revealed that adenine-starved cells were more successful at arresting cell cycle at and sustainig higher survival rate during starvation than leucine-starved cells were. Glucose wasting was also observed during cultivation under adenine-limited conditions. It seems that adenine limitation is physiologically different from other auxotrophic limitations

Possible inhibitory effects of acetate on yeast Kluyveromyces marxianus metabolism

Vājās organiskās skābes spēj inhibēt mikroorganismu augšanu un metabolismu, tādējādi negatīvi ietekmējot biotehnoloģisko procesu efektivitāti. Veicot sūkalu fermentāciju ar raugu Kluyveromyces marxianus un novērojot acetāta uzkrāšanos fermentācijas vidē reizē ar augšanas un fermentācijas ātruma samazināšanos, tika nolemts izpētīt fermentācijās sasniedzamu acetāta koncentrāciju ietekmi uz šī rauga augšanu un metabolismu. Tika demonstrēta acetāta specifiskā inhibējošā iedarbība uz K. marxianus augšanu un metabolismu, kas izpaužas kā paildzināta lag fāze, lēnāka augšana, samazināts biomasas iznākums, traucēts enerģētiskais metabolisms un substrāta patēriņš, augot uz laktozes un galaktozes. Acetāta negatīvās iedarbības stiprums ir atkarīgs no vides pH un augšanas fāzes, un noteiktos apstākļos šūnas adaptējas augstākai acetāta koncentrācijai.Weak organic acids are well known for their potential to inhibit microbial growth and metabolism. As a consequence, they can reduce yields in biotechnological processes. During whey fermentation with yeast Kluyveromyces marxianus accumulation of acetate coincident with reduction in growth and ethanol production was observed, and the effects of biotechnologically relevant acetate concentrations on K. marxianus growth and metabolism were investigated. It was shown that acetate is an inhibitor of growth and metabolism, causing prolonged lag phase, slow growth and reduced biomass yield when utilizing lactose or galactose. It also interfered with carbohydrate catabolism and uptake. The severity of acetate-imposed effects depends on medium pH and growth phase, and yeast cells can acquire elevated tolerance to acetate by adaptation

Antimicrobial Resistance in <i>Enterococcus</i> spp. Isolates from Red Foxes (<i>Vulpes vulpes</i>) in Latvia

Antimicrobial resistance (AMR) is an emerging public health threat and is one of the One Health priorities for humans, animals, and environmental health. Red foxes (Vulpes vulpes) are a widespread predator species with great ecological significance, and they may serve as a sentinel of antimicrobial resistance in the general environment. The present study was carried out to detect antimicrobial resistance, antimicrobial resistance genes, and genetic diversity in faecal isolates of red foxes (Vulpes vulpes). In total, 34 Enterococcus isolates, including E. faecium (n = 17), E. faecalis (n = 12), E. durans (n = 3), and E. hirae (n = 2), were isolated. Antimicrobial resistance to 12 antimicrobial agents was detected with EUVENC panels using the minimum inhibitory concentration (MIC). The presence of antimicrobial resistance genes (ARGs) was determined using whole-genome sequencing (WGS). Resistance to tetracycline (6/34), erythromycin (3/34), ciprofloxacin (2/34), tigecycline (2/34), and daptomycin (2/34) was identified in 44% (15/34) of Enterococcus isolates, while all the isolates were found to be susceptible to ampicillin, chloramphenicol, gentamicin, linezolid, teicoplanin, and vancomycin. No multi-resistant Enterococcus spp. were detected. A total of 12 ARGs were identified in Enterococcus spp., with the presence of at least 1 ARG in every isolate. The identified ARGs encoded resistance to aminoglycosides (aac(6′)-I, ant(6)-Ia, aac(6′)-Iih and spw), tetracyclines (tet(M), tet(L) and tet(S)), and macrolide–lincosamide–streptogramin AB (lnu(B,G), lsa(A,E), and msr(C)), and their presence was associated with phenotypical resistance. Core genome multilocus sequence typing (cgMLST) revealed the high diversity of E. faecalis and E. faecium isolates, even within the same geographical area. The distribution of resistant Enterococcus spp. in wild foxes in Latvia highlights the importance of a One Health approach in tackling AMR

Virulence Determinants and Genetic Diversity of Yersinia Species Isolated from Retail Meat

Yersinia enterocolitica is an important foodborne pathogen, and the determination of its virulence factors and genetic diversity within the food chain could help understand the epidemiology of yersiniosis. The aim of the present study was to detect the prevalence, and characterize the virulence determinants and genetic diversity, of Yersinia species isolated from meat. A total of 330 samples of retailed beef (n = 150) and pork (n = 180) in Latvia were investigated with culture and molecular methods. Whole genome sequencing (WGS) was applied for the detection of virulence and genetic diversity. The antimicrobial resistance of pathogenic Y. enterocolitica isolates was detected in accordance with EUCAST. Yersinia species were isolated from 24% (79/330) of meats, and the prevalence of Y. enterocolitica in pork (24%, 44/180) was significantly higher (p &lt; 0.05) than in beef (13%, 19/150). Y. enterocolitica pathogenic bioserovars 2/O:9 and 4/O:3 were isolated from pork samples (3%, 6/180). Only resistance to ampicillin was confirmed in Y. enterocolitica 4/O:3 and 2/O:9 isolates, but not in other antimicrobials. Major virulence determinants, including ail, inv, virF, ystA and myfA, were confirmed with WGS in Y. enterocolitica 2/O:9 and 4/O:3. MLST typing revealed 15 STs (sequence types) of Y. enterocolitica with ST12 and ST18, which were associated with pathogenic bioserovars. For Y. enterocolitica 1A, Y. kristensenii, Y. intermedia and Y. frederiksenii, novel STs were registered (ST680-688). The presence of virulence genes and genetic characteristics of certain Y. enterocolitica STs confirm the common knowledge that pork could be an important source of pathogenic Yersinia

Prevalence, Genetic Diversity and Factors Associated with Distribution of Listeria monocytogenes and Other Listeria spp. in Cattle Farms in Latvia

Listeria spp. is a diverse genus of Gram-positive bacteria commonly present in the environment while L. monocytogenes and L. ivanovii are well known human and ruminant pathogens. The aim of the present study was to reveal the prevalence and genetic diversity of L. monocytogenes and other Listeria spp. and to identify the factors related to the abundance of pathogen at cattle farms. A total of 521 animal and environmental samples from 27 meat and dairy cattle farms were investigated and the genetic diversity of L. monocytogenes isolates was studied with WGS. The prevalence of Listeria was 58.9%, while of L. monocytogenes it was −11%. The highest prevalence of L. monocytogenes was found in the environment—soil samples near to manure storage (93%), mixed feed from the feeding trough and hay (29%), water samples from farms drinking trough (28%) and cattle feces (28%). Clonal complexes (CC) of CC37 (30%), CC11 (20%) and CC18 (17%) (all IIa serogroup) were predominant L. monocytogenes clones. CC18, CC37 and CC8 were isolated from case farms and CC37, CC11 and CC18 from farms without listeriosis history. Only one hypervirulent CC4 (1%) was isolated from the case farm. Sequence types (STs) were not associated with the isolation source, except for ST7, which was significantly associated with soil (p &lt; 0.05). The contamination of soil, feeding tables and troughs with L. monocytogenes was associated with an increased prevalence of L. monocytogenes at farms. Our study indicates the importance of hygienic practice in the prevention of the dissemination of L. monocytogenes in the cattle farm environment

Prevalence and Genetic Diversity of <i>Legionella</i> spp. in Hotel Water-Supply Systems in Latvia

Legionella is one of the most important waterborne pathogens that can lead to both outbreaks and sporadic cases. The majority of travel-associated Legionnaires’ disease (TALD) cases are contracted during hotel stays. The aim of this study was to evaluate the prevalence and genetic diversity of Legionella spp. in hotel water supply systems in Latvia. In total, 834 hot water samples were collected from the water systems of 80 hotels in Latvia. At least one Legionella spp. positive sample was detected in 47 out of 80 hotels (58.8%). Overall, 235 out of 834 samples (28.2%) were Legionella spp. positive. The average hot water temperature in Latvian hotels was 49.8 °C. The most predominant L. pneumophila serogroup (SG) was SG3 which was found in 113 (49.8%) positive samples from 27 hotels. For 79 sequenced L. pneumophila isolates, 21 different sequence types (ST) were obtained, including 3 new types—ST2582, ST2579, and ST2580. High Legionella contamination and high genetic diversity were found in the hotel water supply systems in Latvia, which, together with the insufficient hot water temperature, may indicate that the lack of regulation and control measures may promote the proliferation of Legionella